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P28700 (RXRA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Retinoic acid receptor RXR-alpha
Alternative name(s):
Nuclear receptor subfamily 2 group B member 1
Retinoid X receptor alpha
Gene names
Name:Rxra
Synonyms:Nr2b1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.4 Ref.6

Subunit structure

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 By similarity. Interacts with coactivator NCOA6, and FAM120B. Interacts with ASXL1 and NCOA1. Ref.1 Ref.3 Ref.5 Ref.7 Ref.8

Subcellular location

Nucleus.

Domain

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

Post-translational modification

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. Ref.4 Ref.6

Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6 By similarity.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis involved in coronary vascular morphogenesis

Traceable author statement PubMed 20299672. Source: DFLAT

cardiac muscle cell differentiation

Traceable author statement PubMed 20299672. Source: DFLAT

cardiac muscle cell proliferation

Traceable author statement PubMed 20299672. Source: DFLAT

embryo implantation

Inferred from genetic interaction PubMed 9892670. Source: MGI

heart development

Traceable author statement PubMed 20299672. Source: DFLAT

heart morphogenesis

Traceable author statement PubMed 20299672. Source: DFLAT

in utero embryonic development

Inferred from genetic interaction PubMed 9892670. Source: MGI

maternal placenta development

Inferred from genetic interaction PubMed 9892670. Source: MGI

mesenchyme development

Traceable author statement PubMed 20299672. Source: DFLAT

modulation by virus of host morphology or physiology

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Traceable author statement PubMed 20299672. Source: DFLAT

negative regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 22001906. Source: MGI

peroxisome proliferator activated receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from mutant phenotype PubMed 9356169. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17107947. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Traceable author statement PubMed 20299672. Source: DFLAT

regulation of branching involved in prostate gland morphogenesis

Inferred from mutant phenotype PubMed 12183441. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 7760852. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15322135. Source: MGI

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

retinoic acid receptor signaling pathway

Inferred from direct assay Ref.2. Source: MGI

secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development

Inferred from mutant phenotype PubMed 12183441. Source: MGI

ventricular cardiac muscle cell differentiation

Inferred from mutant phenotype PubMed 9428411. Source: MGI

ventricular cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 9428411. Source: MGI

visceral serous pericardium development

Traceable author statement PubMed 20299672. Source: DFLAT

   Cellular_componentnuclear chromatin

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 17952069. Source: MGI

   Molecular_function9-cis retinoic acid receptor activity

Inferred from direct assay Ref.2. Source: MGI

DNA binding

Inferred from direct assay PubMed 12015306PubMed 15319426PubMed 15601870PubMed 15681609. Source: MGI

chromatin DNA binding

Inferred from direct assay PubMed 17952069. Source: MGI

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 15322135. Source: MGI

retinoic acid-responsive element binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from genetic interaction PubMed 7823919. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from genetic interaction PubMed 7760852. Source: MGI

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from physical interaction PubMed 17641689. Source: UniProtKB

vitamin D response element binding

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 467467Retinoic acid receptor RXR-alpha
PRO_0000053567

Regions

DNA binding140 – 20566Nuclear receptor
Zinc finger140 – 16021NR C4-type
Zinc finger176 – 20025NR C4-type
Region1 – 139139Modulating domain By similarity
Region206 – 22924Hinge
Region230 – 467238Ligand-binding domain

Amino acid modifications

Modified residue221Phosphoserine Ref.4 Ref.6
Modified residue281Phosphoserine By similarity
Modified residue611Phosphoserine; by MAPK8 and MAPK9 Ref.4
Modified residue751Phosphoserine; by MAPK8 and MAPK9 Ref.4
Modified residue871Phosphothreonine; by MAPK8 and MAPK9 Ref.4
Modified residue2651Phosphoserine; by MAPK8 and MAPK9 Ref.4
Cross-link113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Mutagenesis221S → A: Loss of constituitive phosphorylation. No effect on RXRA transcriptional activity. Ref.4 Ref.6 Ref.7
Mutagenesis441S → A: No effect on constituitive phosphorylation. Ref.4 Ref.7
Mutagenesis481S → A: No effect on constituitive phosphorylation. Ref.4 Ref.7
Mutagenesis541S → A: No effect on constituitive phosphorylation. Ref.4 Ref.7
Mutagenesis611S → 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. Ref.4 Ref.7
Mutagenesis751S → 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. Ref.4 Ref.7
Mutagenesis871T → 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. Ref.4 Ref.7
Mutagenesis961S → A: No effect on constituitive phosphorylation. Ref.4 Ref.7
Mutagenesis1011S → A: No effect on constituitive phosphorylation. Ref.4 Ref.7
Mutagenesis2651S → A: No effect on constiuitive phosphorylation but loss of stress-induced phosphorylation. No effect on RXRA transcriptional activity. Ref.4 Ref.7
Mutagenesis455 – 4562FL → AA: Abolishes interaction with ASXL1 and NCOA1. Ref.7
Mutagenesis459 – 4602ML → AA: Abolishes interaction with ASXL1 and NCOA1. Ref.7

Secondary structure

................................... 467
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P28700 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 0AF62396BCDC87DB

FASTA46751,217
        10         20         30         40         50         60 
MDTKHFLPLD FSTQVNSSSL NSPTGRGSMA VPSLHPSLGP GIGSPLGSPG QLHSPISTLS 

        70         80         90        100        110        120 
SPINGMGPPF SVISSPMGPH SMSVPTTPTL GFGTGSPQLN SPMNPVSSTE DIKPPLGLNG 

       130        140        150        160        170        180 
VLKVPAHPSG NMASFTKHIC AICGDRSSGK HYGVYSCEGC KGFFKRTVRK DLTYTCRDNK 

       190        200        210        220        230        240 
DCLIDKRQRN RCQYCRYQKC LAMGMKREAV QEERQRGKDR NENEVESTSS ANEDMPVEKI 

       250        260        270        280        290        300 
LEAELAVEPK TETYVEANMG LNPSSPNDPV TNICQAADKQ LFTLVEWAKR IPHFSELPLD 

       310        320        330        340        350        360 
DQVILLRAGW NELLIASFSH RSIAVKDGIL LATGLHVHRN SAHSAGVGAI FDRVLTELVS 

       370        380        390        400        410        420 
KMRDMQMDKT ELGCLRAIVL FNPDSKGLSN PAEVEALREK VYASLEAYCK HKYPEQPGRF 

       430        440        450        460 
AKLLLRLPAL RSIGLKCLEH LFFFKLIGDT PIDTFLMEML EAPHQAT 

« Hide

References

[1]"Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently."
Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewsi T., Chen J.Y., Staub A., Garnier J.-M., Mader S., Chambon P.
Cell 68:377-395(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], HETERODIMERIZATION WITH RARA, FUNCTION.
[2]"Characterization of three RXR genes that mediate the action of 9-cis retinoic acid."
Mangelsdorf D.J., Borgmeyer U., Heyman R.A., Zhou J.Y., Ong E.S., Oro A.E., Kakizuka A., Evans R.M.
Genes Dev. 6:329-344(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF LIGAND.
[3]"Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha."
Tontonoz P., Graves R.A., Budavari A.I., Erdjument-Bromage H., Lui M., Hu E., Tempst P., Spiegelman B.M.
Nucleic Acids Res. 22:5628-5634(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 5-16; 27-46; 291-307 AND 446-465, SUBUNIT.
Tissue: Adipose tissue.
[4]"Hyperphosphorylation of the retinoid X receptor alpha by activated c-Jun NH2-terminal kinases."
Adam-Stitah S., Penna L., Chambon P., Rochette-Egly C.
J. Biol. Chem. 274:18932-18941(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-22; SER-61; SER-75; THR-87 AND SER-265, FUNCTION, MUTAGENESIS OF SER-22; SER-44; SER-48; SER-54; SER-61; SER-75; THR-87; SER-96; SER-101 AND SER-265.
[5]"Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR."
Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K.
J. Biol. Chem. 275:13510-13516(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA6.
[6]"The phosphorylation site located in the A region of retinoic X receptor alpha is required for the antiproliferative effect of retinoic acid (RA) and the activation of RA target genes in F9 cells."
Bastien J., Adam-Stitah S., Plassat J.L., Chambon P., Rochette-Egly C.
J. Biol. Chem. 277:28683-28689(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-22, FUNCTION, MUTAGENESIS OF SER-22.
[7]"Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor."
Cho Y.S., Kim E.J., Park U.H., Sin H.S., Um S.J.
J. Biol. Chem. 281:17588-17598(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ASXL1 AND NCOA1, MUTAGENESIS OF 455-PHE-LEU-456 AND 459-MET-LEU-460.
[8]"Constitutive coactivator of peroxisome proliferator-activated receptor (PPARgamma), a novel coactivator of PPARgamma that promotes adipogenesis."
Li D., Kang Q., Wang D.-M.
Mol. Endocrinol. 21:2320-2333(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAM120B.
[9]"Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains."
Bourguet W., Vivat V., Wurtz J.M., Chambon P., Gronemeyer H., Moras D.
Mol. Cell 5:289-298(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 230-462 OF MUTANT ALA-318 IN COMPLEX WITH H.SAPIENS RARA.
[10]"Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies."
Pogenberg V., Guichou J.F., Vivat-Hannah V., Kammerer S., Perez E., Germain P., de Lera A.R., Gronemeyer H., Royer C.A., Bourguet W.
J. Biol. Chem. 280:1625-1633(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 230-467 IN COMPLEX WITH RARB AND MED1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M84817 mRNA. Translation: AAA40080.1.
X66223 mRNA. Translation: CAA46962.1.
PIRS26668.
RefSeqNP_035435.1. NM_011305.3.
UniGeneMm.24624.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DKFX-ray2.50A230-462[»]
1XDKX-ray2.90A/E230-467[»]
3A9EX-ray2.75A228-467[»]
ProteinModelPortalP28700.
SMRP28700. Positions 137-464.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203038. 15 interactions.
IntActP28700. 14 interactions.
MINTMINT-2775018.

Chemistry

BindingDBP28700.
ChEMBLCHEMBL3084.
GuidetoPHARMACOLOGY610.

PTM databases

PhosphoSiteP28700.

Proteomic databases

PaxDbP28700.
PRIDEP28700.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000077257; ENSMUSP00000076491; ENSMUSG00000015846.
ENSMUST00000166775; ENSMUSP00000133044; ENSMUSG00000015846.
GeneID20181.
KEGGmmu:20181.
UCSCuc008ixs.1. mouse.

Organism-specific databases

CTD6256.
MGIMGI:98214. Rxra.

Phylogenomic databases

eggNOGNOG327099.
GeneTreeENSGT00740000115010.
HOGENOMHOG000260821.
HOVERGENHBG005606.
InParanoidP28700.
KOK08524.
OMAKHFLPLD.
PhylomeDBP28700.
TreeFamTF352097.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.
REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

Gene expression databases

ArrayExpressP28700.
BgeeP28700.
CleanExMM_RXRA.
GenevestigatorP28700.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR021780. Nuc_recep-AF1.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR000003. Retinoid-X_rcpt/HNF4.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF11825. Nuc_recep-AF1. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00545. RETINOIDXR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRXRA. mouse.
EvolutionaryTraceP28700.
NextBio297705.
PROP28700.
SOURCESearch...

Entry information

Entry nameRXRA_MOUSE
AccessionPrimary (citable) accession number: P28700
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: April 16, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot