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P10276

- RARA_HUMAN

UniProt

P10276 - RARA_HUMAN

Protein

Retinoic acid receptor alpha

Gene

RARA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 189 (01 Oct 2014)
      Sequence version 2 (01 Oct 1989)
      Previous versions | rss
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    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

    1. chromatin DNA binding Source: UniProtKB
    2. drug binding Source: Ensembl
    3. enzyme binding Source: UniProtKB
    4. mRNA 5'-UTR binding Source: Ensembl
    5. phosphatidylinositol 3-kinase regulator activity Source: Ensembl
    6. protein binding Source: UniProtKB
    7. protein domain specific binding Source: UniProtKB
    8. protein heterodimerization activity Source: UniProtKB
    9. protein kinase A binding Source: UniProtKB
    10. protein kinase B binding Source: UniProtKB
    11. receptor binding Source: UniProtKB
    12. retinoic acid binding Source: BHF-UCL
    13. retinoic acid receptor activity Source: BHF-UCL
    14. retinoic acid-responsive element binding Source: UniProtKB
    15. sequence-specific DNA binding Source: InterPro
    16. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    17. steroid hormone receptor activity Source: InterPro
    18. transcription coactivator activity Source: UniProtKB
    19. transcription corepressor activity Source: UniProtKB
    20. transcription factor binding Source: UniProtKB
    21. translation repressor activity, nucleic acid binding Source: Ensembl
    22. zinc ion binding Source: InterPro

    GO - Biological processi

    1. apoptotic cell clearance Source: UniProtKB
    2. cellular response to estrogen stimulus Source: UniProtKB
    3. cellular response to lipopolysaccharide Source: Ensembl
    4. cellular response to retinoic acid Source: UniProtKB
    5. chondroblast differentiation Source: Ensembl
    6. female pregnancy Source: Ensembl
    7. gene expression Source: Reactome
    8. germ cell development Source: Ensembl
    9. growth plate cartilage development Source: Ensembl
    10. intracellular estrogen receptor signaling pathway Source: BHF-UCL
    11. liver development Source: Ensembl
    12. multicellular organism growth Source: Ensembl
    13. negative regulation of cartilage development Source: Ensembl
    14. negative regulation of cell proliferation Source: Ensembl
    15. negative regulation of granulocyte differentiation Source: UniProtKB
    16. negative regulation of interferon-gamma production Source: BHF-UCL
    17. negative regulation of transcription, DNA-templated Source: UniProtKB
    18. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    19. negative regulation of translational initiation Source: Ensembl
    20. negative regulation of tumor necrosis factor production Source: BHF-UCL
    21. positive regulation of binding Source: UniProtKB
    22. positive regulation of cell cycle Source: UniProtKB
    23. positive regulation of cell proliferation Source: UniProtKB
    24. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
    25. positive regulation of interleukin-13 production Source: BHF-UCL
    26. positive regulation of interleukin-4 production Source: BHF-UCL
    27. positive regulation of interleukin-5 production Source: BHF-UCL
    28. positive regulation of neuron differentiation Source: Ensembl
    29. positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
    30. positive regulation of protein kinase B signaling Source: Ensembl
    31. positive regulation of T-helper 2 cell differentiation Source: BHF-UCL
    32. positive regulation of transcription, DNA-templated Source: UniProtKB
    33. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    34. prostate gland development Source: Ensembl
    35. protein phosphorylation Source: UniProtKB
    36. regulation of apoptotic process Source: Ensembl
    37. regulation of myelination Source: Ensembl
    38. regulation of synaptic plasticity Source: Ensembl
    39. response to cytokine Source: Ensembl
    40. response to estradiol Source: BHF-UCL
    41. response to ethanol Source: Ensembl
    42. response to retinoic acid Source: BHF-UCL
    43. response to vitamin A Source: Ensembl
    44. retinoic acid receptor signaling pathway Source: BHF-UCL
    45. Sertoli cell fate commitment Source: Ensembl
    46. signal transduction Source: BHF-UCL
    47. spermatogenesis Source: Ensembl
    48. transcription initiation from RNA polymerase II promoter Source: Reactome
    49. ureteric bud development Source: Ensembl
    50. ventricular cardiac muscle cell differentiation Source: Ensembl

    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.
    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: 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

    1. cell surface Source: BHF-UCL
    2. cytoplasm Source: UniProtKB
    3. dendrite Source: Ensembl
    4. neuronal cell body Source: Ensembl
    5. nuclear chromatin Source: BHF-UCL
    6. nucleoplasm Source: Reactome
    7. nucleus Source: UniProtKB
    8. perinuclear region of cytoplasm Source: Ensembl

    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.
    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.
    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.

    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

    ArrayExpressiP10276.
    BgeeiP10276.
    CleanExiHS_RARA.
    GenevestigatoriP10276.

    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.By similarity14 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
    MED1Q156482EBI-413374,EBI-394459
    MED25Q71SY510EBI-413374,EBI-394558
    NCOA1Q157883EBI-413374,EBI-455189
    PHF8Q9UPP1-22EBI-413374,EBI-6601215
    RXRAP197934EBI-413374,EBI-78598
    RXRGP484433EBI-413374,EBI-712405
    SIRT1Q96EB63EBI-413374,EBI-1802965
    SUMO1P631655EBI-413374,EBI-80140
    ZNF423Q2M1K92EBI-413374,EBI-950016

    Protein-protein interaction databases

    BioGridi111849. 117 interactions.
    DIPiDIP-34N.
    IntActiP10276. 30 interactions.
    MINTiMINT-123081.
    STRINGi9606.ENSP00000254066.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000010312.
    HOVERGENiHBG005606.
    KOiK08527.
    OMAiNNSSDQR.
    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. Align

    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

    MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV    50
    SGYSTPSPAT IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY 100
    GVSACEGCKG FFRRSIQKNM VYTCHRDKNC IINKVTRNRC QYCRLQKCFE 150
    VGMSKESVRN DRNKKKKEVP KPECSESYTL TPEVGELIEK VRKAHQETFP 200
    ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV EFAKQLPGFT 250
    TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA 300
    GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDRVDM 350
    LQEPLLEALK VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM 400
    EIPGSMPPLI QEMLENSEGL DTLSGQPGGG GRDGGGLAPP PGSCSPSLSP 450
    SSNRSSPATH SP 462
    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.
    The sequence AAB00113.1 differs from that shown. Reason: Erroneous initiation.
    The sequence BAB62809.1 differs from that shown. Reason: Erroneous initiation.

    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:
    EMBL
    GenBank
    DDBJ
    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]
    XP_005257612.1. XM_005257555.1. [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]

    Polymorphism databases

    DMDMi133483.

    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:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS11366.1. [P10276-1 ]
    CCDS42317.1. [P10276-2 ]
    CCDS45671.1. [P10276-3 ]
    PIRi A29491.
    RefSeqi NP_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 ]
    UniGenei Hs.654583.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1DKF X-ray 2.50 B 182-416 [» ]
    1DSZ X-ray 1.70 A 82-167 [» ]
    3A9E X-ray 2.75 B 153-421 [» ]
    3KMR X-ray 1.80 A 176-421 [» ]
    3KMZ X-ray 2.10 A/B 176-421 [» ]
    4DQM X-ray 2.75 A/C 182-415 [» ]
    ProteinModelPortali P10276.
    SMRi P10276. Positions 87-415.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111849. 117 interactions.
    DIPi DIP-34N.
    IntActi P10276. 30 interactions.
    MINTi MINT-123081.
    STRINGi 9606.ENSP00000254066.

    Chemistry

    BindingDBi P10276.
    ChEMBLi CHEMBL2363071.
    DrugBanki DB00459. Acitretin.
    DB00210. Adapalene.
    DB00523. Alitretinoin.
    DB00926. Etretinate.
    DB00982. Isotretinoin.
    DB04942. Tamibarotene.
    DB00799. Tazarotene.
    GuidetoPHARMACOLOGYi 590.

    PTM databases

    PhosphoSitei P10276.

    Polymorphism databases

    DMDMi 133483.

    Proteomic databases

    MaxQBi P10276.
    PaxDbi P10276.
    PRIDEi P10276.

    Protocols and materials databases

    DNASUi 5914.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000254066 ; ENSP00000254066 ; ENSG00000131759 . [P10276-1 ]
    ENST00000394081 ; ENSP00000377643 ; ENSG00000131759 . [P10276-2 ]
    ENST00000394089 ; ENSP00000377649 ; ENSG00000131759 . [P10276-1 ]
    ENST00000425707 ; ENSP00000389993 ; ENSG00000131759 . [P10276-3 ]
    GeneIDi 5914.
    KEGGi hsa:5914.
    UCSCi uc002huk.2. human. [P10276-1 ]
    uc010wfe.2. human. [P10276-3 ]

    Organism-specific databases

    CTDi 5914.
    GeneCardsi GC17P038465.
    HGNCi HGNC:9864. RARA.
    MIMi 180240. gene.
    612376. phenotype.
    neXtProti NX_P10276.
    Orphaneti 520. Acute promyelocytic leukemia.
    PharmGKBi PA34225.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG297448.
    HOGENOMi HOG000010312.
    HOVERGENi HBG005606.
    KOi K08527.
    OMAi NNSSDQR.
    PhylomeDBi P10276.
    TreeFami TF328382.

    Enzyme and pathway databases

    Reactomei REACT_15525. Nuclear Receptor transcription pathway.
    SignaLinki P10276.

    Miscellaneous databases

    ChiTaRSi RARA. human.
    EvolutionaryTracei P10276.
    GeneWikii Retinoic_acid_receptor_alpha.
    GenomeRNAii 5914.
    NextBioi 23018.
    PROi P10276.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P10276.
    Bgeei P10276.
    CleanExi HS_RARA.
    Genevestigatori P10276.

    Family and domain databases

    Gene3Di 1.10.565.10. 1 hit.
    3.30.50.10. 1 hit.
    InterProi IPR008946. 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 ]
    Pfami PF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view ]
    PRINTSi PR01292. RETNOICACIDR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTi SM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 1 hit.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. "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.

    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: October 1, 2014
    This is version 189 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