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P10276 (RARA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 187. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Retinoic acid receptor alpha

Short name=RAR-alpha
Alternative name(s):
Nuclear receptor subfamily 1 group B member 1
Gene names
Name:RARA
Synonyms:NR1B1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length462 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 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. Ref.19 Ref.22 Ref.23 Ref.24

Subunit structure

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. Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.27

Subcellular location

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. Ref.17 Ref.22

Domain

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

Post-translational modification

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. Ref.19 Ref.24

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. Ref.17 Ref.22

Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation.

Ubiquitinated.

Involvement in disease

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.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

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

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

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

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DiseaseProto-oncogene
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell fate commitment

Inferred from electronic annotation. Source: Ensembl

apoptotic cell clearance

Inferred from mutant phenotype PubMed 19628791. Source: UniProtKB

cellular response to estrogen stimulus

Inferred from direct assay PubMed 20080953. Source: UniProtKB

cellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

cellular response to retinoic acid

Inferred from direct assay PubMed 19917671. Source: UniProtKB

chondroblast differentiation

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

germ cell development

Inferred from electronic annotation. Source: Ensembl

growth plate cartilage development

Inferred from electronic annotation. Source: Ensembl

intracellular estrogen receptor signaling pathway

Inferred from direct assay PubMed 15831516. Source: BHF-UCL

liver development

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cartilage development

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of granulocyte differentiation

Inferred from direct assay PubMed 19917671. Source: UniProtKB

negative regulation of interferon-gamma production

Inferred from direct assay PubMed 18416830. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 20080953. Source: UniProtKB

negative regulation of translational initiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of tumor necrosis factor production

Inferred from direct assay PubMed 18416830. Source: BHF-UCL

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of T-helper 2 cell differentiation

Inferred from direct assay PubMed 18416830. Source: BHF-UCL

positive regulation of binding

Inferred from mutant phenotype PubMed 20080953. Source: UniProtKB

positive regulation of cell cycle

Inferred from mutant phenotype PubMed 20080953. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 20080953. Source: UniProtKB

positive regulation of interleukin-13 production

Inferred from direct assay PubMed 18416830. Source: BHF-UCL

positive regulation of interleukin-4 production

Inferred from direct assay PubMed 18416830. Source: BHF-UCL

positive regulation of interleukin-5 production

Inferred from direct assay PubMed 18416830. Source: BHF-UCL

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.22. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18845237Ref.22PubMed 20080953. Source: UniProtKB

prostate gland development

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from mutant phenotype PubMed 16456540. Source: UniProtKB

regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

regulation of myelination

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from direct assay PubMed 15831516. Source: BHF-UCL

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from mutant phenotype PubMed 17538076. Source: BHF-UCL

response to vitamin A

Inferred from electronic annotation. Source: Ensembl

retinoic acid receptor signaling pathway

Inferred from mutant phenotype PubMed 17538076. Source: BHF-UCL

signal transduction

Inferred from direct assay Ref.8. Source: BHF-UCL

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

ventricular cardiac muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell surface

Inferred by curator Ref.8. Source: BHF-UCL

cytoplasm

Inferred from direct assay Ref.22. Source: UniProtKB

dendrite

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nuclear chromatin

Inferred from direct assay PubMed 17363140. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 18845237PubMed 19917671PubMed 20080953. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchromatin DNA binding

Inferred from direct assay PubMed 19917671. Source: UniProtKB

drug binding

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction Ref.15PubMed 9628876. Source: UniProtKB

mRNA 5'-UTR binding

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase regulator activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 16456540Ref.23Ref.22PubMed 19917671PubMed 20080953PubMed 9653119. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 20413580. Source: UniProtKB

protein heterodimerization activity

Inferred from direct assay PubMed 19917671. Source: UniProtKB

protein kinase A binding

Inferred from direct assay Ref.24. Source: UniProtKB

protein kinase B binding

Inferred from physical interaction Ref.19. Source: UniProtKB

receptor binding

Inferred from direct assay PubMed 19628791. Source: UniProtKB

retinoic acid binding

Inferred from direct assay Ref.8. Source: BHF-UCL

retinoic acid receptor activity

Inferred from direct assay Ref.8. Source: BHF-UCL

retinoic acid-responsive element binding

Inferred from direct assay PubMed 19917671. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 18922886PubMed 20413580. Source: UniProtKB

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription coactivator activity

Inferred from direct assay PubMed 20080953. Source: UniProtKB

transcription corepressor activity

Inferred from direct assay PubMed 20080953. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 17641689. Source: UniProtKB

translation repressor activity, nucleic acid binding

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha-1 (identifier: P10276-1)

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.
Isoform Alpha-2 (identifier: P10276-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MASNSSSCPT...SGYSTPSPAT → MYESVEVGGP...TPLWNGSNHS
Isoform Alpha-1-deltaBC (identifier: P10276-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 462462Retinoic acid receptor alpha
PRO_0000053461

Regions

DNA binding88 – 15366Nuclear receptor
Zinc finger88 – 10821NR C4-type
Zinc finger124 – 14825NR C4-type
Region1 – 8787Modulating
Region154 – 19946Hinge
Region200 – 419220Ligand-binding
Region404 – 41916Required for binding corepressor NCOR1

Sites

Site60 – 612Breakpoint for translocation to form PLZF-RAR-alpha, RAR-alpha1-PLZF and PML-RAR-alpha oncogenes

Amino acid modifications

Modified residue771Phosphoserine; by CDK7 By similarity
Modified residue961Phosphoserine; by PKB/AKT1 Ref.19
Modified residue2191Phosphoserine; by PKA Ref.24
Modified residue3691Phosphoserine; by PKA Ref.24
Cross-link166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22
Cross-link171Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22
Cross-link399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22

Natural variations

Alternative sequence1 – 6060MASNS…PSPAT → MYESVEVGGPTPNPFLVVDF YNQNRACLLPEKGLPAPGPY STPLRTPLWNGSNHS in isoform Alpha-2.
VSP_003629
Alternative sequence61 – 15797Missing in isoform Alpha-1-deltaBC.
VSP_043143

Experimental info

Mutagenesis951S → A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation. Ref.19
Mutagenesis961S → A: Abolishes PKB/AKT1-mediated phosphorylation. Repressed transactivation. Ref.19
Mutagenesis1471K → 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. Ref.22
Mutagenesis1541S → A: No effect on PKB/AKT1-mediated phosphorylation. No repression of transactivation. Ref.19
Mutagenesis1571S → A: No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation. Ref.19
Mutagenesis1661K → 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. Ref.22
Mutagenesis1711K → 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. Ref.22
Mutagenesis2191S → A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-369. Ref.24
Mutagenesis2191S → 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. Ref.24
Mutagenesis3691S → A: No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-219. Ref.24
Mutagenesis3691S → 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. Ref.24
Mutagenesis3961I → 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. Ref.27
Mutagenesis3991K → 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. Ref.22
Mutagenesis409 – 4102LI → AA: Abolishes interaction with ASXL1 and NCOA1.
Mutagenesis4121E → Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-415. Ref.20
Mutagenesis413 – 4142ML → AA: Abolishes interaction with ASXL1 and NCOA1.
Mutagenesis4151E → Q: Impairs interaction with ASXL1 and NCOA1; when associated with Q-412. Ref.20
Sequence conflict2411E → D in AAD05222. Ref.3

Secondary structure

............................................. 462
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha-1 [UniParc].

Last modified October 1, 1989. Version 2.
Checksum: E8D1CF9A1E57CB99

FASTA46250,771
        10         20         30         40         50         60 
MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV SGYSTPSPAT 

        70         80         90        100        110        120 
IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM 

       130        140        150        160        170        180 
VYTCHRDKNC IINKVTRNRC QYCRLQKCFE VGMSKESVRN DRNKKKKEVP KPECSESYTL 

       190        200        210        220        230        240 
TPEVGELIEK VRKAHQETFP ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV 

       250        260        270        280        290        300 
EFAKQLPGFT TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA 

       310        320        330        340        350        360 
GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDRVDM LQEPLLEALK 

       370        380        390        400        410        420 
VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGL 

       430        440        450        460 
DTLSGQPGGG GRDGGGLAPP PGSCSPSLSP SSNRSSPATH SP 

« Hide

Isoform Alpha-2 [UniParc].

Checksum: 1E328ED7945D1F95
Show »

FASTA45750,742
Isoform Alpha-1-deltaBC [UniParc].

Checksum: D24F282D50E9953E
Show »

FASTA36539,700

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"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.
[26]"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.
[27]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06614 mRNA. Translation: CAA29829.1.
X06538 mRNA. Translation: CAA29787.1.
AF088895 expand/collapse EMBL AC list , 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.
CCDSCCDS11366.1. [P10276-1]
CCDS42317.1. [P10276-2]
CCDS45671.1. [P10276-3]
PIRA29491.
RefSeqNP_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]
XP_005257612.1. XM_005257555.1. [P10276-1]
UniGeneHs.654583.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP10276.
SMRP10276. Positions 87-415.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111849. 114 interactions.
DIPDIP-34N.
IntActP10276. 28 interactions.
MINTMINT-123081.
STRING9606.ENSP00000254066.

Chemistry

BindingDBP10276.
ChEMBLCHEMBL2363071.
DrugBankDB00459. Acitretin.
DB00210. Adapalene.
DB00523. Alitretinoin.
DB00926. Etretinate.
DB00982. Isotretinoin.
DB04942. Tamibarotene.
DB00799. Tazarotene.
GuidetoPHARMACOLOGY590.

PTM databases

PhosphoSiteP10276.

Polymorphism databases

DMDM133483.

Proteomic databases

MaxQBP10276.
PaxDbP10276.
PRIDEP10276.

Protocols and materials databases

DNASU5914.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000254066; ENSP00000254066; ENSG00000131759. [P10276-1]
ENST00000394081; ENSP00000377643; ENSG00000131759. [P10276-2]
ENST00000394089; ENSP00000377649; ENSG00000131759. [P10276-1]
ENST00000425707; ENSP00000389993; ENSG00000131759. [P10276-3]
GeneID5914.
KEGGhsa:5914.
UCSCuc002huk.2. human. [P10276-1]
uc010wfe.2. human. [P10276-3]

Organism-specific databases

CTD5914.
GeneCardsGC17P038465.
HGNCHGNC:9864. RARA.
MIM180240. gene.
612376. phenotype.
neXtProtNX_P10276.
Orphanet520. Acute promyelocytic leukemia.
PharmGKBPA34225.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297448.
HOGENOMHOG000010312.
HOVERGENHBG005606.
KOK08527.
OMANNSSDQR.
PhylomeDBP10276.
TreeFamTF328382.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP10276.

Gene expression databases

ArrayExpressP10276.
BgeeP10276.
CleanExHS_RARA.
GenevestigatorP10276.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR008946. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01292. RETNOICACIDR.
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

ChiTaRSRARA. human.
EvolutionaryTraceP10276.
GeneWikiRetinoic_acid_receptor_alpha.
GenomeRNAi5914.
NextBio23018.
PROP10276.
SOURCESearch...

Entry information

Entry nameRARA_HUMAN
AccessionPrimary (citable) accession number: P10276
Secondary accession number(s): B8Y636 expand/collapse secondary AC list , P78456, Q13440, Q13441, Q96S41, Q9NQS0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 1, 1989
Last modified: July 9, 2014
This is version 187 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM