P28700 · RXRA_MOUSE
- ProteinRetinoic acid receptor RXR-alpha
- GeneRxra
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids467 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Receptor for retinoic acid that acts as a transcription factor (PubMed:10383391, PubMed:12032153, PubMed:25417649).
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:10383391, PubMed:1310259).
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:1310259).
The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:10383391, PubMed:25417649).
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 (PubMed:1310259).
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 (By similarity).
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 (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 (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 (PubMed:10383391, PubMed:1310259).
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:1310259).
The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:10383391, PubMed:25417649).
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 (PubMed:1310259).
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 (By similarity).
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 (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 (By similarity).
Features
Showing features for binding site, dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 140 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
DNA binding | 140-205 | Nuclear receptor | ||||
Sequence: CAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGM | ||||||
Binding site | 143 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 157 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 160 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 176 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 182 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 192 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 195 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 321 | 9-cis-retinoate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 321 | all-trans-retinoate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 332 | 9-cis-retinoate (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 332 | all-trans-retinoate (UniProtKB | ChEBI) | ||||
Sequence: A |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRetinoic acid receptor RXR-alpha
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP28700
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
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).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Reduced myelin debris uptake by bone marrow-derived macrophages (PubMed:26463675).
Conditional knockout in myeloid cells results in reduced myelin debris clearing by macrophages, delayed oligodendrocyte progenitor cell differentiation and slowern remyelination after induced focal demyelination (PubMed:26463675).
Conditional knockout in myeloid cells results in reduced myelin debris clearing by macrophages, delayed oligodendrocyte progenitor cell differentiation and slowern remyelination after induced focal demyelination (PubMed:26463675).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 22 | Loss of constituitive phosphorylation. No effect on RXRA transcriptional activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 44 | No effect on constituitive phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 48 | No effect on constituitive phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 54 | No effect on constituitive phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 61 | 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. | ||||
Sequence: S → A | ||||||
Mutagenesis | 75 | 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. | ||||
Sequence: S → A | ||||||
Mutagenesis | 87 | 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. | ||||
Sequence: T → A | ||||||
Mutagenesis | 96 | No effect on constituitive phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 101 | No effect on constituitive phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 265 | No effect on constiuitive phosphorylation but loss of stress-induced phosphorylation. No effect on RXRA transcriptional activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 455-456 | Abolishes interaction with ASXL1 and NCOA1. | ||||
Sequence: FL → AA | ||||||
Mutagenesis | 459-460 | Abolishes interaction with ASXL1 and NCOA1. | ||||
Sequence: ML → AA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 10 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000053567 | 1-467 | Retinoic acid receptor RXR-alpha | |||
Sequence: MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQAT | ||||||
Cross-link | 4 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 22 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 28 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 61 | Phosphoserine; by MAPK8 and MAPK9 | ||||
Sequence: S | ||||||
Modified residue | 75 | Phosphoserine; by MAPK8 and MAPK9 | ||||
Sequence: S | ||||||
Modified residue | 87 | Phosphothreonine; by MAPK8 and MAPK9 | ||||
Sequence: T | ||||||
Cross-link | 113 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Modified residue | 134 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 150 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 264 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 265 | Phosphoserine; by MAPK8 and MAPK9 | ||||
Sequence: S |
Post-translational modification
Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity.
Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain (PubMed:10383391, PubMed:12032153).
Constitutively phosphorylated on Ser-22 in the presence or absence of ligand (PubMed:10383391, PubMed:12032153).
Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265 (PubMed:10383391).
Phosphorylated on Ser-28, in vitro, by PKA (By similarity).
This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (By similarity).
Constitutively phosphorylated on Ser-22 in the presence or absence of ligand (PubMed:10383391, PubMed:12032153).
Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265 (PubMed:10383391).
Phosphorylated on Ser-28, in vitro, by PKA (By similarity).
This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (By similarity).
Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound RXRA when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation.
Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homodimer (By similarity).
Heterodimer with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity (PubMed:10882070).
Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (By similarity).
Heterodimerizes with PPARG (PubMed:7838715).
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 coactivator NCO6 (PubMed:10788465).
Interacts with coactivator NCO3 (By similarity).
Interacts with coactivator FAM120B (PubMed:17595322).
Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By similarity).
Interacts with PRMT2 (By similarity).
Interacts with ASXL1 (PubMed:16606617).
Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (By similarity).
Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:15528208, PubMed:16606617).
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 (via 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 (PubMed:20078863).
Heterodimer with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity (PubMed:10882070).
Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (By similarity).
Heterodimerizes with PPARG (PubMed:7838715).
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 coactivator NCO6 (PubMed:10788465).
Interacts with coactivator NCO3 (By similarity).
Interacts with coactivator FAM120B (PubMed:17595322).
Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By similarity).
Interacts with PRMT2 (By similarity).
Interacts with ASXL1 (PubMed:16606617).
Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (By similarity).
Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:15528208, PubMed:16606617).
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 (via 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 (PubMed:20078863).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P28700 | Asxl1 P59598 | 2 | EBI-346715, EBI-5743705 | |
XENO | P28700 | ASXL1 Q8IXJ9 | 2 | EBI-346715, EBI-1646500 | |
XENO | P28700 | MED25 Q71SY5 | 3 | EBI-346715, EBI-394558 | |
XENO | P28700 | SFPQ P23246-1 | 3 | EBI-346715, EBI-355463 | |
BINARY | P28700 | Sqstm1 Q64337 | 3 | EBI-346715, EBI-645025 | |
XENO | P28700 | SQSTM1 Q13501 | 3 | EBI-346715, EBI-307104 | |
XENO | P28700 | VDR P11473 | 3 | EBI-346715, EBI-286357 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, zinc finger, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-112 | Disordered | ||||
Sequence: MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDI | ||||||
Region | 1-139 | Modulating domain | ||||
Sequence: MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHI | ||||||
Compositional bias | 9-28 | Polar residues | ||||
Sequence: LDFSTQVNSSSLNSPTGRGS | ||||||
Compositional bias | 50-68 | Polar residues | ||||
Sequence: GQLHSPISTLSSPINGMGP | ||||||
Compositional bias | 76-108 | Polar residues | ||||
Sequence: PMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSS | ||||||
Zinc finger | 140-160 | NR C4-type | ||||
Sequence: CAICGDRSSGKHYGVYSCEGC | ||||||
Region | 165-170 | Nuclear localization signal | ||||
Sequence: KRTVRK | ||||||
Zinc finger | 176-200 | NR C4-type | ||||
Sequence: CRDNKDCLIDKRQRNRCQYCRYQKC | ||||||
Region | 206-229 | Hinge | ||||
Sequence: KREAVQEERQRGKDRNENEVESTS | ||||||
Compositional bias | 211-227 | Basic and acidic residues | ||||
Sequence: QEERQRGKDRNENEVES | ||||||
Region | 211-233 | Disordered | ||||
Sequence: QEERQRGKDRNENEVESTSSANE | ||||||
Domain | 232-463 | NR LBD | ||||
Sequence: NEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAP | ||||||
Region | 353-373 | Required for nuclear export | ||||
Sequence: RVLTELVSKMRDMQMDKTELG |
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.
Sequence similarities
Belongs to the nuclear hormone receptor family. NR2 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length467
- Mass (Da)51,217
- Last updated1992-12-01 v1
- Checksum0AF62396BCDC87DB
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A2AJP2 | A2AJP2_MOUSE | Rxra | 165 | ||
A0A5F8MP91 | A0A5F8MP91_MOUSE | Rxra | 322 | ||
A0A5F8MQ23 | A0A5F8MQ23_MOUSE | Rxra | 497 | ||
Q6LC96 | Q6LC96_MOUSE | Rxra | 439 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 9-28 | Polar residues | ||||
Sequence: LDFSTQVNSSSLNSPTGRGS | ||||||
Compositional bias | 50-68 | Polar residues | ||||
Sequence: GQLHSPISTLSSPINGMGP | ||||||
Compositional bias | 76-108 | Polar residues | ||||
Sequence: PMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSS | ||||||
Compositional bias | 211-227 | Basic and acidic residues | ||||
Sequence: QEERQRGKDRNENEVES |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M84817 EMBL· GenBank· DDBJ | AAA40080.1 EMBL· GenBank· DDBJ | mRNA | ||
X66223 EMBL· GenBank· DDBJ | CAA46962.1 EMBL· GenBank· DDBJ | mRNA |