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Protein

Retinoic acid receptor alpha

Gene

RARA

Organism
Homo sapiens (Human)
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 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. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.By similarity4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei60 – 612Breakpoint for translocation to form PLZF-RAR-alpha, RAR-alpha1-PLZF and PML-RAR-alpha oncogenes

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi88 – 15366Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri88 – 10821NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri124 – 14825NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • alpha-actinin binding Source: UniProtKB
  • chromatin DNA binding Source: UniProtKB
  • drug binding Source: Ensembl
  • enzyme binding Source: UniProtKB
  • mRNA 5'-UTR binding Source: Ensembl
  • phosphatidylinositol 3-kinase regulator activity Source: Ensembl
  • protein domain specific binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein kinase A binding Source: UniProtKB
  • protein kinase B binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • retinoic acid binding Source: BHF-UCL
  • retinoic acid receptor activity Source: BHF-UCL
  • retinoic acid-responsive element binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: Ensembl
  • sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • steroid hormone receptor activity Source: InterPro
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • translation repressor activity, nucleic acid binding Source: Ensembl
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_15525. Nuclear Receptor transcription pathway.
REACT_267785. Signaling by Retinoic Acid.
SignaLinkiP10276.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoic acid receptor alpha
Short name:
RAR-alpha
Alternative name(s):
Nuclear receptor subfamily 1 group B member 1
Gene namesi
Name:RARA
Synonyms:NR1B1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:9864. RARA.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Nuclear localization depends on ligand binding, phosphorylation and sumoylation. Transloaction to the nucleus in the absence of ligand is dependent on activation of PKC and the downstream MAPK phosphorylation.

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • cell surface Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • dendrite Source: Ensembl
  • neuronal cell body Source: Ensembl
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi95 – 951S → A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation. 1 Publication
Mutagenesisi96 – 961S → A: Abolishes PKB/AKT1-mediated phosphorylation. Repressed transactivation. 1 Publication
Mutagenesisi147 – 1471K → R: Abrogates sumoylation in the presence or absence of ATRA and primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-166; R-171 and R-399. 1 Publication
Mutagenesisi154 – 1541S → A: No effect on PKB/AKT1-mediated phosphorylation. No repression of transactivation. 1 Publication
Mutagenesisi157 – 1571S → A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation. 1 Publication
Mutagenesisi166 – 1661K → R: Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-171 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-171 and R-399. 1 Publication
Mutagenesisi171 – 1711K → R: Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-166 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-399. 1 Publication
Mutagenesisi219 – 2191S → A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-369. 1 Publication
Mutagenesisi219 – 2191S → E: No effect on heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, no increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-369. 1 Publication
Mutagenesisi369 – 3691S → A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-219. 1 Publication
Mutagenesisi369 – 3691S → E: Some inhibition of heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-219. 1 Publication
Mutagenesisi396 – 3961I → E: Abrogates interaction with NCOR1 or NCOR2. Increased affinity for NCOR1 and NCOR2 in the presence of BMS493. Increased transcriptional activity in the presence of agonist and decreased activity in the presence of neutral antagonist. 1 Publication
Mutagenesisi399 – 3991K → R in the absence of ATRA, abolishes sumoylation and is mainly nuclear. In the presence of ATRA, some sumoylation, cytoplasmic location, reduced transcriptional activity and no SENP6 binding. Low sumoylation levels in the presence of ATRA and nuclear location in the absence of ATRA; when associated with R-166 or with R-171. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-171. 1 Publication
Mutagenesisi409 – 4102LI → AA: Abolishes interaction with ASXL1 and NCOA1. 1 Publication
Mutagenesisi412 – 4121E → Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-415. 1 Publication
Mutagenesisi413 – 4142ML → AA: Abolishes interaction with ASXL1 and NCOA1. 1 Publication
Mutagenesisi415 – 4151E → Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-412. 1 Publication

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

MIMi612376. phenotype.
Orphaneti520. Acute promyelocytic leukemia.
PharmGKBiPA34225.

Chemistry

DrugBankiDB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00982. Isotretinoin.
DB04942. Tamibarotene.
DB00799. Tazarotene.

Polymorphism and mutation databases

BioMutaiRARA.
DMDMi133483.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 462462Retinoic acid receptor alphaPRO_0000053461Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei77 – 771Phosphoserine; by CDK7By similarity
Modified residuei96 – 961Phosphoserine; by PKB/AKT11 Publication
Cross-linki166 – 166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Cross-linki171 – 171Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei219 – 2191Phosphoserine; by PKA1 Publication
Modified residuei369 – 3691Phosphoserine; by PKA1 Publication
Cross-linki399 – 399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Post-translational modificationi

Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity (By similarity). Phosphorylation by AKT1 is required for the repressor activity but has no effect on DNA binding, protein stability nor subcellular localization. Phosphorylated by PKA in vitro. This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and transcriptional activity in response to FSH signaling.By similarity2 Publications
Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171. Probably desumoylated by SENP6. Sumoylation levels determine nuclear localization and regulate ATRA-mediated transcriptional activity.2 Publications
Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation.
Ubiquitinated.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP10276.
PaxDbiP10276.
PRIDEiP10276.

PTM databases

PhosphoSiteiP10276.

Expressioni

Gene expression databases

BgeeiP10276.
CleanExiHS_RARA.
ExpressionAtlasiP10276. baseline and differential.
GenevisibleiP10276. HS.

Interactioni

Subunit structurei

Heterodimer; with RXRA. Binds DNA preferentially as a heterodimer. Interacts with CDK7 (By similarity). Interacts with coactivators NCOA3 and NCOA6. Interacts with NCOA7; the interaction requires ligand-binding. Interacts with KMT2E/MLL5. Interacts (via the ligand-binding domain) with PRAME; the interaction is ligand (retinoic acid)-dependent. Interacts with AKT1; the interaction phosphorylates RARA and represses transactivation. Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity. Interacts with NCOR1 and NCOR2. Interacts with PRMT2. Interacts with LRIF1. Interacts with ASXL1 and NCOA1. Interacts with ACTN4.By similarity15 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Asxl1P595984EBI-413374,EBI-5743705From a different organism.
EZH2Q159102EBI-413374,EBI-530054
GNAQP501484EBI-413374,EBI-3909604
ITGB1BP2Q9UKP32EBI-413374,EBI-5659717
MED1Q156483EBI-413374,EBI-394459
MED25Q71SY510EBI-413374,EBI-394558
NCOA1Q157883EBI-413374,EBI-455189
NCOA3Q9Y6Q92EBI-413374,EBI-81196
NCOR1O753763EBI-413374,EBI-347233
NRIP1P485524EBI-413374,EBI-746484
PHF8Q9UPP1-22EBI-413374,EBI-6601215
PRKDCP785273EBI-413374,EBI-352053
RXRAP197936EBI-413374,EBI-78598
RXRBP287024EBI-413374,EBI-748576
RXRGP4844310EBI-413374,EBI-712405
SIRT1Q96EB63EBI-413374,EBI-1802965
SUMO1P631655EBI-413374,EBI-80140
TEKT4Q8WW243EBI-10197061,EBI-750487
ZNF423Q2M1K92EBI-413374,EBI-950016

Protein-protein interaction databases

BioGridi111849. 122 interactions.
DIPiDIP-34N.
IntActiP10276. 52 interactions.
MINTiMINT-123081.
STRINGi9606.ENSP00000254066.

Structurei

Secondary structure

1
462
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni89 – 913Combined sources
Beta strandi97 – 993Combined sources
Helixi106 – 11712Combined sources
Turni134 – 1363Combined sources
Helixi137 – 1393Combined sources
Helixi141 – 15010Combined sources
Helixi155 – 1573Combined sources
Helixi183 – 19614Combined sources
Helixi202 – 2043Combined sources
Beta strandi214 – 2163Combined sources
Helixi222 – 24423Combined sources
Helixi249 – 2513Combined sources
Helixi254 – 27522Combined sources
Turni279 – 2824Combined sources
Beta strandi283 – 2853Combined sources
Beta strandi289 – 2935Combined sources
Helixi294 – 3007Combined sources
Helixi303 – 3053Combined sources
Helixi306 – 31611Combined sources
Helixi317 – 3193Combined sources
Helixi323 – 33412Combined sources
Helixi345 – 36622Combined sources
Helixi373 – 40129Combined sources
Beta strandi402 – 4043Combined sources
Helixi408 – 4147Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DKFX-ray2.50B182-416[»]
1DSZX-ray1.70A82-167[»]
3A9EX-ray2.75B153-421[»]
3KMRX-ray1.80A176-421[»]
3KMZX-ray2.10A/B176-421[»]
4DQMX-ray2.75A/C182-415[»]
ProteinModelPortaliP10276.
SMRiP10276. Positions 87-415.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10276.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 8787ModulatingAdd
BLAST
Regioni154 – 19946HingeAdd
BLAST
Regioni200 – 419220Ligand-bindingAdd
BLAST
Regioni404 – 41916Required for binding corepressor NCOR1Add
BLAST

Domaini

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

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri88 – 10821NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri124 – 14825NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG297448.
GeneTreeiENSGT00780000121834.
HOGENOMiHOG000010312.
HOVERGENiHBG005606.
InParanoidiP10276.
KOiK08527.
OMAiFLMVDYY.
PhylomeDBiP10276.
TreeFamiTF328382.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003078. Retinoic_acid_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01292. RETNOICACIDR.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-1 (identifier: P10276-1) [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
MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV
60 70 80 90 100
SGYSTPSPAT IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY
110 120 130 140 150
GVSACEGCKG FFRRSIQKNM VYTCHRDKNC IINKVTRNRC QYCRLQKCFE
160 170 180 190 200
VGMSKESVRN DRNKKKKEVP KPECSESYTL TPEVGELIEK VRKAHQETFP
210 220 230 240 250
ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV EFAKQLPGFT
260 270 280 290 300
TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA
310 320 330 340 350
GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDRVDM
360 370 380 390 400
LQEPLLEALK VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM
410 420 430 440 450
EIPGSMPPLI QEMLENSEGL DTLSGQPGGG GRDGGGLAPP PGSCSPSLSP
460
SSNRSSPATH SP
Length:462
Mass (Da):50,771
Last modified:October 1, 1989 - v2
Checksum:iE8D1CF9A1E57CB99
GO
Isoform Alpha-2 (identifier: P10276-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MASNSSSCPT...SGYSTPSPAT → MYESVEVGGP...TPLWNGSNHS

Show »
Length:457
Mass (Da):50,742
Checksum:i1E328ED7945D1F95
GO
Isoform Alpha-1-deltaBC (identifier: P10276-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     61-157: Missing.

Note: Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1.
Show »
Length:365
Mass (Da):39,700
Checksum:iD24F282D50E9953E
GO

Sequence cautioni

The sequence AAB00112.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAB00113.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAB62809.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti241 – 2411E → D in AAD05222 (PubMed:10337631).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6060MASNS…PSPAT → MYESVEVGGPTPNPFLVVDF YNQNRACLLPEKGLPAPGPY STPLRTPLWNGSNHS in isoform Alpha-2. 1 PublicationVSP_003629Add
BLAST
Alternative sequencei61 – 15797Missing in isoform Alpha-1-deltaBC. 1 PublicationVSP_043143Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06614 mRNA. Translation: CAA29829.1.
X06538 mRNA. Translation: CAA29787.1.
AF088895
, AF088889, AF088890, AF088891, AF088892, AF088893, AF088894 Genomic DNA. Translation: AAD05222.1.
FJ487576 mRNA. Translation: ACK86665.1.
AC080112 Genomic DNA. No translation available.
BC008727 mRNA. Translation: AAH08727.1.
BC071733 mRNA. Translation: AAH71733.1.
X56058, X58685 mRNA. Translation: CAA39533.1.
X58685 mRNA. Translation: CAA41532.1.
U41742 mRNA. Translation: AAB00112.1. Different initiation.
U41743 mRNA. Translation: AAB00113.1. Different initiation.
AF283809 Genomic DNA. Translation: AAF87249.1.
AB067754 mRNA. Translation: BAB62809.1. Different initiation.
CCDSiCCDS11366.1. [P10276-1]
CCDS42317.1. [P10276-2]
CCDS45671.1. [P10276-3]
PIRiA29491.
RefSeqiNP_000955.1. NM_000964.3. [P10276-1]
NP_001019980.1. NM_001024809.3. [P10276-2]
NP_001138773.1. NM_001145301.2.
NP_001138774.1. NM_001145302.2. [P10276-3]
XP_005257610.1. XM_005257553.1. [P10276-1]
XP_005257611.1. XM_005257554.1. [P10276-1]
UniGeneiHs.654583.

Genome annotation databases

EnsembliENST00000254066; ENSP00000254066; ENSG00000131759. [P10276-1]
ENST00000394081; ENSP00000377643; ENSG00000131759. [P10276-2]
ENST00000394089; ENSP00000377649; ENSG00000131759. [P10276-1]
ENST00000425707; ENSP00000389993; ENSG00000131759. [P10276-3]
GeneIDi5914.
KEGGihsa:5914.
UCSCiuc002huk.2. human. [P10276-1]
uc010wfe.2. human. [P10276-3]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

Retinoic acid receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06614 mRNA. Translation: CAA29829.1.
X06538 mRNA. Translation: CAA29787.1.
AF088895
, AF088889, AF088890, AF088891, AF088892, AF088893, AF088894 Genomic DNA. Translation: AAD05222.1.
FJ487576 mRNA. Translation: ACK86665.1.
AC080112 Genomic DNA. No translation available.
BC008727 mRNA. Translation: AAH08727.1.
BC071733 mRNA. Translation: AAH71733.1.
X56058, X58685 mRNA. Translation: CAA39533.1.
X58685 mRNA. Translation: CAA41532.1.
U41742 mRNA. Translation: AAB00112.1. Different initiation.
U41743 mRNA. Translation: AAB00113.1. Different initiation.
AF283809 Genomic DNA. Translation: AAF87249.1.
AB067754 mRNA. Translation: BAB62809.1. Different initiation.
CCDSiCCDS11366.1. [P10276-1]
CCDS42317.1. [P10276-2]
CCDS45671.1. [P10276-3]
PIRiA29491.
RefSeqiNP_000955.1. NM_000964.3. [P10276-1]
NP_001019980.1. NM_001024809.3. [P10276-2]
NP_001138773.1. NM_001145301.2.
NP_001138774.1. NM_001145302.2. [P10276-3]
XP_005257610.1. XM_005257553.1. [P10276-1]
XP_005257611.1. XM_005257554.1. [P10276-1]
UniGeneiHs.654583.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DKFX-ray2.50B182-416[»]
1DSZX-ray1.70A82-167[»]
3A9EX-ray2.75B153-421[»]
3KMRX-ray1.80A176-421[»]
3KMZX-ray2.10A/B176-421[»]
4DQMX-ray2.75A/C182-415[»]
ProteinModelPortaliP10276.
SMRiP10276. Positions 87-415.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111849. 122 interactions.
DIPiDIP-34N.
IntActiP10276. 52 interactions.
MINTiMINT-123081.
STRINGi9606.ENSP00000254066.

Chemistry

BindingDBiP10276.
ChEMBLiCHEMBL2363072.
DrugBankiDB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00982. Isotretinoin.
DB04942. Tamibarotene.
DB00799. Tazarotene.
GuidetoPHARMACOLOGYi590.

PTM databases

PhosphoSiteiP10276.

Polymorphism and mutation databases

BioMutaiRARA.
DMDMi133483.

Proteomic databases

MaxQBiP10276.
PaxDbiP10276.
PRIDEiP10276.

Protocols and materials databases

DNASUi5914.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254066; ENSP00000254066; ENSG00000131759. [P10276-1]
ENST00000394081; ENSP00000377643; ENSG00000131759. [P10276-2]
ENST00000394089; ENSP00000377649; ENSG00000131759. [P10276-1]
ENST00000425707; ENSP00000389993; ENSG00000131759. [P10276-3]
GeneIDi5914.
KEGGihsa:5914.
UCSCiuc002huk.2. human. [P10276-1]
uc010wfe.2. human. [P10276-3]

Organism-specific databases

CTDi5914.
GeneCardsiGC17P038465.
HGNCiHGNC:9864. RARA.
MIMi180240. gene.
612376. phenotype.
neXtProtiNX_P10276.
Orphaneti520. Acute promyelocytic leukemia.
PharmGKBiPA34225.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG297448.
GeneTreeiENSGT00780000121834.
HOGENOMiHOG000010312.
HOVERGENiHBG005606.
InParanoidiP10276.
KOiK08527.
OMAiFLMVDYY.
PhylomeDBiP10276.
TreeFamiTF328382.

Enzyme and pathway databases

ReactomeiREACT_15525. Nuclear Receptor transcription pathway.
REACT_267785. Signaling by Retinoic Acid.
SignaLinkiP10276.

Miscellaneous databases

ChiTaRSiRARA. human.
EvolutionaryTraceiP10276.
GeneWikiiRetinoic_acid_receptor_alpha.
GenomeRNAii5914.
NextBioi23018.
PROiP10276.
SOURCEiSearch...

Gene expression databases

BgeeiP10276.
CleanExiHS_RARA.
ExpressionAtlasiP10276. baseline and differential.
GenevisibleiP10276. HS.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003078. Retinoic_acid_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01292. RETNOICACIDR.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a receptor for the morphogen retinoic acid."
    Giguere V., Ong E.S., Segui P., Evans R.M.
    Nature 330:624-629(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
  2. "PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors."
    Chen Z., Guidez F., Rousselot P., Agadir A., Chen S.-J., Wang Z.-Y., Degos L., Zelent A., Waxman S., Chomienne C.
    Proc. Natl. Acad. Sci. U.S.A. 91:1178-1182(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1), CHROMOSOMAL TRANSLOCATION WITH PML.
  3. "Genomic structure of the human retinoic acid receptor-alpha1 gene."
    Hjalt T.A.H., Murray J.C.
    Mamm. Genome 10:528-529(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA-1).
  4. "Retinoic acid receptor alpha1 variants, RARalpha1DeltaB and RARalpha1DeltaBC, define a new class of nuclear receptor isoforms."
    Parrado A., Despouy G., Kraiba R., Le Pogam C., Dupas S., Choquette M., Robledo M., Larghero J., Bui H., Le Gall I., Rochette-Egly C., Chomienne C., Padua R.A.
    Nucleic Acids Res. 29:4901-4908(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1-DELTABC).
  5. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
    Tissue: Blood and Brain.
  7. "Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha)."
    Brand N.J., Petkovich M., Chambon P.
    Nucleic Acids Res. 18:6799-6806(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-80 (ISOFORM ALPHA-1).
  8. "A human retinoic acid receptor which belongs to the family of nuclear receptors."
    Petkovich M., Brand N.J., Krust A., Chambon P.
    Nature 330:444-450(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-462.
  9. Chambon P.
    Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  10. "The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion."
    Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J.
    Blood 87:882-886(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-462, CHROMOSOMAL TRANSLOCATION WITH NPM.
    Tissue: Bone marrow.
  11. "Homo sapiens retinoic acid receptor alpha (RAR-alpha) gene, promoter and 5' region of RAR-alpha 2 isoform."
    Chen A., Petrie K., Waxman S., Zelent A.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54 (ISOFORM ALPHA-2).
  12. "Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: structure of the fusion point in a case lacking classic t(15;17) translocation."
    Fujita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K., Omine M.
    Leuk. Lymphoma 44:111-115(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-68, CHROMOSOMAL TRANSLOCATION WITH PML.
  13. "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300."
    Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., Privalsky M.L., Nakatani Y., Evans R.M.
    Cell 90:569-580(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA3.
  14. "A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo."
    Lee S.-K., Anzick S.L., Choi J.-E., Bubendorf L., Guan X.-Y., Jung Y.-K., Kallioniemi O.-P., Kononen J., Trent J.M., Azorsa D., Jhun B.-H., Cheong J.H., Lee Y.C., Meltzer P.S., Lee J.W.
    J. Biol. Chem. 274:34283-34293(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA6.
  15. "Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha."
    Qi C., Chang J., Zhu Y., Yeldandi A.V., Rao S.M., Zhu Y.-J.
    J. Biol. Chem. 277:28624-28630(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRMT2.
  16. "ERAP140, a conserved tissue-specific nuclear receptor coactivator."
    Shao W., Halachmi S., Brown M.
    Mol. Cell. Biol. 22:3358-3372(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA7.
  17. "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation."
    Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.
    Biochem. Biophys. Res. Commun. 330:746-754(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF THE PML-RARALPHA ONCOPROTEIN WITH UBE2I, SUMOYLATION, SUBCELLULAR LOCATION.
  18. "The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling."
    Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R.
    Cell 122:835-847(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRAME.
  19. "Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha."
    Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L., Weigel N.L., Brown P.H., Kurie J.M.
    Biochem. J. 395:653-662(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-96, FUNCTION, INTERACTION WITH AKT1, MUTAGENESIS OF SER-95; SER-96; SER-154 AND SER-157.
  20. "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 409-ILE-LEU-410; GLU-412; 413-MET-LEU-414 AND GLU-415.
  21. "RIF-1, a novel nuclear receptor corepressor that associates with the nuclear matrix."
    Li H.J., Haque Z.K., Chen A., Mendelsohn M.
    J. Cell. Biochem. 102:1021-1035(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LRIF1.
  22. "Small ubiquitin-like modifier-2 modification of retinoic acid receptor-alpha regulates its subcellular localization and transcriptional activity."
    Zhu L., Santos N.C., Kim K.H.
    Endocrinology 150:5586-5595(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-166; LYS-171 AND LYS-399, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-147; LYS-166; LYS-171 AND LYS-399.
  23. "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis."
    Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., Kitagawa H., Kato S.
    Nature 459:455-459(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH KMT2E.
  24. "Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling."
    Santos N.C., Kim K.H.
    Endocrinology 151:2361-2372(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-219 AND SER-369, INTERACTION WITH RXRA AND PRKAR1A, FUNCTION, MUTAGENESIS OF SER-219 AND SER-369.
  25. "Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors."
    Khurana S., Chakraborty S., Lam M., Liu Y., Su Y.T., Zhao X., Saleem M.A., Mathieson P.W., Bruggeman L.A., Kao H.Y.
    J. Biol. Chem. 287:12027-12035(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ACTN4.
  26. "Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1."
    Rastinejad F., Wagner T., Zhao Q., Khorasanizadeh S.
    EMBO J. 19:1045-1054(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 82-167 IN COMPLEX WITH RXRA AND DNA.
  27. "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 182-416 IN COMPLEX WITH M.MUSCULUS RXRA.
  28. "A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor."
    le Maire A., Teyssier C., Erb C., Grimaldi M., Alvarez S., de Lera A.R., Balaguer P., Gronemeyer H., Royer C.A., Germain P., Bourguet W.
    Nat. Struct. Mol. Biol. 17:801-807(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 176-421 IN COMPLEXES WITH AGONIST AM580 AND NCOA1 AND WITH INVERSE AGONIST BMS493 AND NCOR1, INTERACTION WITH NCOR1 AND NCOR2, MUTAGENESIS OF ILE-396.

Entry informationi

Entry nameiRARA_HUMAN
AccessioniPrimary (citable) accession number: P10276
Secondary accession number(s): B8Y636
, P78456, Q13440, Q13441, Q96S41, Q9NQS0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 1, 1989
Last modified: June 24, 2015
This is version 198 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.