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
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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.4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi135 – 200Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri135 – 155NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri171 – 195NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • 9-cis retinoic acid receptor activity Source: ProtInc
  • chromatin DNA binding Source: Ensembl
  • DBD domain binding Source: CAFA
  • DNA binding Source: MGI
  • DNA binding transcription factor activity Source: UniProtKB
  • double-stranded DNA binding Source: CAFA
  • enzyme binding Source: UniProtKB
  • LBD domain binding Source: CAFA
  • ligand-dependent nuclear receptor binding Source: CAFA
  • nuclear receptor activity Source: BHF-UCL
  • peptide binding Source: CAFA
  • protein heterodimerization activity Source: UniProtKB
  • retinoic acid binding Source: CAFA
  • retinoic acid receptor activity Source: BHF-UCL
  • retinoic acid-responsive element binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: AgBase
  • steroid hormone receptor activity Source: InterPro
  • transcription coactivator activity Source: ProtInc
  • vitamin D receptor binding Source: BHF-UCL
  • zinc ion binding Source: CAFA

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processHost-virus interaction, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1368082 RORA activates gene expression
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-159418 Recycling of bile acids and salts
R-HSA-192105 Synthesis of bile acids and bile salts
R-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781 PPARA activates gene expression
R-HSA-200425 Import of palmitoyl-CoA into the mitochondrial matrix
R-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex
R-HSA-211976 Endogenous sterols
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-400253 Circadian Clock
R-HSA-5362517 Signaling by Retinoic Acid
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis
SignaLinkiP19793
SIGNORiP19793

Chemistry databases

SwissLipidsiSLP:000001552

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000186350.9
HGNCiHGNC:10477 RXRA
MIMi180245 gene
neXtProtiNX_P19793

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27S → A: Abolishes phosphorylation. No change in increase of RARA-mediated transcriptional activity. 2 Publications1
Mutagenesisi27S → A: Increase in RARA-mediated transcriptional activity. 2 Publications1

Organism-specific databases

DisGeNETi6256
OpenTargetsiENSG00000186350
PharmGKBiPA34890

Chemistry databases

ChEMBLiCHEMBL2061
DrugBankiDB07863 2-chloro-5-nitro-N-phenylbenzamide
DB00459 Acitretin
DB00210 Adapalene
DB00523 Alitretinoin
DB00307 Bexarotene
DB00749 Etodolac
DB00926 Etretinate
DB08601 tributylstannanyl
GuidetoPHARMACOLOGYi610

Polymorphism and mutation databases

BioMutaiRXRA
DMDMi133701

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535661 – 462Retinoic acid receptor RXR-alphaAdd BLAST462

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki4Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei21PhosphoserineBy similarity1
Modified residuei27Phosphoserine1 Publication1
Modified residuei56Phosphoserine; by MAPK8 and MAPK9By similarity1
Modified residuei70Phosphoserine; by MAPK8 and MAPK9By similarity1
Modified residuei82Phosphothreonine; by MAPK8 and MAPK9By similarity1
Cross-linki108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei129PhosphoserineCombined sources1
Modified residuei259PhosphoserineCombined sources1
Modified residuei260Phosphoserine; by MAPK8 and MAPK9By similarity1

Post-translational modificationi

Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain. Constiutively phosphorylated on Ser-21 in the presence or absence of ligand. 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. This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA.By similarity1 Publication
Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP19793
MaxQBiP19793
PaxDbiP19793
PeptideAtlasiP19793
PRIDEiP19793

PTM databases

iPTMnetiP19793
PhosphoSitePlusiP19793

Miscellaneous databases

PMAP-CutDBP19793

Expressioni

Tissue specificityi

Highly expressed in liver, also found in lung, kidney and heart.

Gene expression databases

BgeeiENSG00000186350
CleanExiHS_RXRA
ExpressionAtlasiP19793 baseline and differential
GenevisibleiP19793 HS

Organism-specific databases

HPAiCAB004565
CAB005352

Interactioni

Subunit structurei

Homodimer. 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. Interacts with NCOA3 and NCOA6 coactivators. Interacts with FAM120B (By similarity). Interacts with PELP1, SENP6, SFPQ, DNTTIP2 and RNF8. 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. Interacts with PRMT2. Interacts with ASXL1 (By similarity). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2. Interacts in a ligand-dependent fashion with MED1 and NCOA1. Interacts with VDR.By similarity16 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • DBD domain binding Source: CAFA
  • enzyme binding Source: UniProtKB
  • LBD domain binding Source: CAFA
  • ligand-dependent nuclear receptor binding Source: CAFA
  • protein heterodimerization activity Source: UniProtKB
  • vitamin D receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112168, 118 interactors
CORUMiP19793
DIPiDIP-641N
ELMiP19793
IntActiP19793, 49 interactors
MINTiP19793
STRINGi9606.ENSP00000419692

Chemistry databases

BindingDBiP19793

Structurei

Secondary structure

1462
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi131 – 134Combined sources4
Turni136 – 138Combined sources3
Beta strandi141 – 146Combined sources6
Beta strandi149 – 151Combined sources3
Helixi153 – 165Combined sources13
Beta strandi172 – 175Combined sources4
Turni181 – 186Combined sources6
Helixi188 – 197Combined sources10
Helixi202 – 204Combined sources3
Helixi226 – 229Combined sources4
Helixi232 – 241Combined sources10
Helixi246 – 250Combined sources5
Turni251 – 253Combined sources3
Beta strandi258 – 261Combined sources4
Helixi264 – 284Combined sources21
Helixi289 – 291Combined sources3
Helixi294 – 316Combined sources23
Helixi317 – 319Combined sources3
Beta strandi320 – 325Combined sources6
Turni327 – 329Combined sources3
Beta strandi331 – 333Combined sources3
Helixi334 – 339Combined sources6
Turni340 – 342Combined sources3
Helixi343 – 352Combined sources10
Helixi354 – 360Combined sources7
Helixi364 – 375Combined sources12
Beta strandi380 – 382Combined sources3
Helixi386 – 407Combined sources22
Helixi414 – 419Combined sources6
Helixi422 – 441Combined sources20
Beta strandi447 – 449Combined sources3
Helixi450 – 454Combined sources5
Helixi457 – 459Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BY4X-ray2.10A/B/C/D129-209[»]
1DSZX-ray1.70B129-212[»]
1FBYX-ray2.25A/B224-462[»]
1FM6X-ray2.10A/U225-462[»]
1FM9X-ray2.10A225-462[»]
1G1UX-ray2.50A/B/C/D225-462[»]
1G5YX-ray2.00A/B/C/D225-462[»]
1K74X-ray2.30A225-462[»]
1LBDX-ray2.70A201-460[»]
1MV9X-ray1.90A223-462[»]
1MVCX-ray1.90A223-462[»]
1MZNX-ray1.90A/C/E/G223-462[»]
1R0NX-ray2.60A130-206[»]
1RDTX-ray2.40A225-462[»]
1RXRNMR-A130-212[»]
1XLSX-ray2.96A/B/C/D227-458[»]
1XV9X-ray2.70A/C227-462[»]
1XVPX-ray2.60A/C227-462[»]
1YNWX-ray3.00B130-228[»]
2ACLX-ray2.80A/C/E/G225-462[»]
2NLLX-ray1.90A135-200[»]
2P1TX-ray1.80A223-462[»]
2P1UX-ray2.20A223-462[»]
2P1VX-ray2.20A223-462[»]
2ZXZX-ray3.00A223-462[»]
2ZY0X-ray2.90A/C223-462[»]
3DZUX-ray3.20A11-462[»]
3DZYX-ray3.10A11-462[»]
3E00X-ray3.10A11-462[»]
3E94X-ray1.90A223-462[»]
3FALX-ray2.36A/C225-462[»]
3FC6X-ray2.06A/C225-462[»]
3FUGX-ray2.00A223-462[»]
3H0AX-ray2.10A228-455[»]
3KWYX-ray2.30A223-462[»]
3NSPX-ray2.90A/B223-462[»]
3NSQX-ray2.60A/B223-462[»]
3OAPX-ray2.05A228-458[»]
3OZJX-ray2.10A/C225-462[»]
3PCUX-ray2.00A229-458[»]
3R29X-ray2.90A/B223-462[»]
3R2AX-ray3.00A/B/C/D223-462[»]
3R5MX-ray2.80A/C223-462[»]
3UVVX-ray2.95B225-462[»]
4CN2X-ray2.07C/D130-212[»]
4CN3X-ray2.35A/B/C130-212[»]
D130-173[»]
D175-212[»]
4CN5X-ray2.00A/B130-212[»]
4CN7X-ray2.34A/B/E/F130-212[»]
4J5WX-ray2.80C/D227-462[»]
4J5XX-ray2.80C/D227-462[»]
4K4JX-ray2.00A228-458[»]
4K6IX-ray2.10A228-458[»]
4M8EX-ray2.40A228-458[»]
4M8HX-ray2.20A228-458[»]
4N5GX-ray2.11A/B/C/D223-462[»]
4N8RX-ray2.03A/B/C/D223-462[»]
4NQAX-ray3.10A/H98-462[»]
4OC7X-ray2.50A223-462[»]
4POHX-ray2.30A228-458[»]
4POJX-ray2.00A228-458[»]
4PP3X-ray2.00A228-458[»]
4PP5X-ray2.00A228-458[»]
4RFWX-ray2.40A228-458[»]
4RMCX-ray2.70A228-458[»]
4RMDX-ray1.90A228-462[»]
4RMEX-ray2.30A228-462[»]
4ZO1X-ray3.22B231-455[»]
4ZSHX-ray1.80A223-462[»]
5EC9X-ray2.30A229-456[»]
5GYMX-ray2.60A/B/C/D/E/F/G/H227-462[»]
5JI0X-ray1.98A223-462[»]
5LYQX-ray2.17A223-462[»]
5MJ5X-ray1.90A229-457[»]
5MK4X-ray2.00A/C229-457[»]
5MKJX-ray2.50A229-458[»]
5MKUX-ray1.78A229-456[»]
5MMWX-ray2.70A229-457[»]
5TBPX-ray2.60A/B/C/D223-462[»]
5UANX-ray3.51A98-462[»]
DisProtiDP00062
ProteinModelPortaliP19793
SMRiP19793
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19793

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini227 – 458NR LBDPROSITE-ProRule annotationAdd BLAST232

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 134ModulatingBy similarityAdd BLAST134
Regioni201 – 224HingeAdd BLAST24

Domaini

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

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri135 – 155NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri171 – 195NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118948
HOVERGENiHBG005606
InParanoidiP19793
KOiK08524
OMAiLTCGMKR
OrthoDBiEOG091G0YX6
PhylomeDBiP19793
TreeFamiTF352097

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF11825 Nuc_recep-AF1, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00545 RETINOIDXR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19793-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDTKHFLPLD FSTQVNSSLT SPTGRGSMAA PSLHPSLGPG IGSPGQLHSP
60 70 80 90 100
ISTLSSPING MGPPFSVISS PMGPHSMSVP TTPTLGFSTG SPQLSSPMNP
110 120 130 140 150
VSSSEDIKPP LGLNGVLKVP AHPSGNMASF TKHICAICGD RSSGKHYGVY
160 170 180 190 200
SCEGCKGFFK RTVRKDLTYT CRDNKDCLID KRQRNRCQYC RYQKCLAMGM
210 220 230 240 250
KREAVQEERQ RGKDRNENEV ESTSSANEDM PVERILEAEL AVEPKTETYV
260 270 280 290 300
EANMGLNPSS PNDPVTNICQ AADKQLFTLV EWAKRIPHFS ELPLDDQVIL
310 320 330 340 350
LRAGWNELLI ASFSHRSIAV KDGILLATGL HVHRNSAHSA GVGAIFDRVL
360 370 380 390 400
TELVSKMRDM QMDKTELGCL RAIVLFNPDS KGLSNPAEVE ALREKVYASL
410 420 430 440 450
EAYCKHKYPE QPGRFAKLLL RLPALRSIGL KCLEHLFFFK LIGDTPIDTF
460
LMEMLEAPHQ MT
Length:462
Mass (Da):50,811
Last modified:February 1, 1991 - v1
Checksum:i7F952B580AD84C42
GO
Isoform 2 (identifier: P19793-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-97: Missing.

Note: No experimental confirmation available.
Show »
Length:365
Mass (Da):41,060
Checksum:i6F0D30787329986D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014620261P → L. Corresponds to variant dbSNP:rs2234960Ensembl.1
Natural variantiVAR_050582327A → S. Corresponds to variant dbSNP:rs1805345Ensembl.1
Natural variantiVAR_014621336S → I. Corresponds to variant dbSNP:rs1805345Ensembl.1
Natural variantiVAR_050583398A → V. Corresponds to variant dbSNP:rs11542209Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0565651 – 97Missing in isoform 2. 1 PublicationAdd BLAST97

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52773 mRNA Translation: CAA36982.1
AB307705 mRNA Translation: BAH02296.1
AK131192 mRNA Translation: BAG54745.1
AC156789 Genomic DNA No translation available.
AL354796 Genomic DNA No translation available.
AL669970 Genomic DNA No translation available.
AL683798 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW88123.1
BC110998 mRNA Translation: AAI10999.1
DQ303444 Genomic DNA Translation: ABB96254.1
CCDSiCCDS35172.1 [P19793-1]
PIRiS09592
RefSeqiNP_001278850.1, NM_001291921.1 [P19793-2]
NP_002948.1, NM_002957.5 [P19793-1]
UniGeneiHs.590886

Genome annotation databases

EnsembliENST00000481739; ENSP00000419692; ENSG00000186350 [P19793-1]
GeneIDi6256
KEGGihsa:6256
UCSCiuc004cfb.3 human [P19793-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRXRA_HUMAN
AccessioniPrimary (citable) accession number: P19793
Secondary accession number(s): B3KY83, Q2NL52, Q2V504
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: May 23, 2018
This is version 217 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health