ID RARA_HUMAN Reviewed; 462 AA.
AC P10276; B8Y636; P78456; Q13440; Q13441; Q96S41; Q9NQS0;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 27-MAR-2024, entry version 266.
DE RecName: Full=Retinoic acid receptor alpha;
DE Short=RAR-alpha;
DE AltName: Full=Nuclear receptor subfamily 1 group B member 1;
GN Name=RARA; Synonyms=NR1B1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
RX PubMed=2825036; DOI=10.1038/330624a0;
RA Giguere V., Ong E.S., Segui P., Evans R.M.;
RT "Identification of a receptor for the morphogen retinoic acid.";
RL Nature 330:624-629(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1), AND CHROMOSOMAL TRANSLOCATION
RP WITH PML.
RX PubMed=8302850; DOI=10.1073/pnas.91.3.1178;
RA Chen Z., Guidez F., Rousselot P., Agadir A., Chen S.-J., Wang Z.-Y.,
RA Degos L., Zelent A., Waxman S., Chomienne C.;
RT "PLZF-RAR alpha fusion proteins generated from the variant
RT t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit
RT ligand-dependent transactivation of wild-type retinoic acid receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:1178-1182(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA-1).
RX PubMed=10337631; DOI=10.1007/s003359901036;
RA Hjalt T.A.H., Murray J.C.;
RT "Genomic structure of the human retinoic acid receptor-alpha1 gene.";
RL Mamm. Genome 10:528-529(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1-DELTABC).
RX PubMed=11812818; DOI=10.1093/nar/29.24.4901;
RA Parrado A., Despouy G., Kraiba R., Le Pogam C., Dupas S., Choquette M.,
RA Robledo M., Larghero J., Bui H., Le Gall I., Rochette-Egly C.,
RA Chomienne C., Padua R.A.;
RT "Retinoic acid receptor alpha1 variants, RARalpha1DeltaB and
RT RARalpha1DeltaBC, define a new class of nuclear receptor isoforms.";
RL Nucleic Acids Res. 29:4901-4908(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
RC TISSUE=Blood, and Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-80 (ISOFORM ALPHA-1).
RX PubMed=2175878; DOI=10.1093/nar/18.23.6799;
RA Brand N.J., Petkovich M., Chambon P.;
RT "Characterization of a functional promoter for the human retinoic acid
RT receptor-alpha (hRAR-alpha).";
RL Nucleic Acids Res. 18:6799-6806(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-462.
RX PubMed=2825025; DOI=10.1038/330444a0;
RA Petkovich M., Brand N.J., Krust A., Chambon P.;
RT "A human retinoic acid receptor which belongs to the family of nuclear
RT receptors.";
RL Nature 330:444-450(1987).
RN [9]
RP SEQUENCE REVISION.
RA Chambon P.;
RL Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-462, AND CHROMOSOMAL TRANSLOCATION WITH
RP NPM.
RC TISSUE=Bone marrow;
RX PubMed=8562957;
RA Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J.;
RT "The t(5;17) variant of acute promyelocytic leukemia expresses a
RT nucleophosmin-retinoic acid receptor fusion.";
RL Blood 87:882-886(1996).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54 (ISOFORM ALPHA-2).
RA Chen A., Petrie K., Waxman S., Zelent A.;
RT "Homo sapiens retinoic acid receptor alpha (RAR-alpha) gene, promoter and
RT 5' region of RAR-alpha 2 isoform.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-68, AND CHROMOSOMAL TRANSLOCATION WITH
RP PML.
RX PubMed=12691149; DOI=10.1080/1042819021000040305;
RA Fujita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K., Omine M.;
RT "Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia:
RT structure of the fusion point in a case lacking classic t(15;17)
RT translocation.";
RL Leuk. Lymphoma 44:111-115(2003).
RN [13]
RP FUNCTION, AND INTERACTION WITH NCOA3.
RX PubMed=9267036; DOI=10.1016/s0092-8674(00)80516-4;
RA Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L.,
RA Privalsky M.L., Nakatani Y., Evans R.M.;
RT "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and
RT forms a multimeric activation complex with P/CAF and CBP/p300.";
RL Cell 90:569-580(1997).
RN [14]
RP INTERACTION WITH NCOA6.
RX PubMed=10567404; DOI=10.1074/jbc.274.48.34283;
RA Lee S.-K., Anzick S.L., Choi J.-E., Bubendorf L., Guan X.-Y., Jung Y.-K.,
RA Kallioniemi O.-P., Kononen J., Trent J.M., Azorsa D., Jhun B.-H.,
RA Cheong J.H., Lee Y.C., Meltzer P.S., Lee J.W.;
RT "A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator
RT essential for ligand-dependent transactivation by nuclear receptors in
RT vivo.";
RL J. Biol. Chem. 274:34283-34293(1999).
RN [15]
RP INTERACTION WITH PRMT2.
RX PubMed=12039952; DOI=10.1074/jbc.m201053200;
RA Qi C., Chang J., Zhu Y., Yeldandi A.V., Rao S.M., Zhu Y.-J.;
RT "Identification of protein arginine methyltransferase 2 as a coactivator
RT for estrogen receptor alpha.";
RL J. Biol. Chem. 277:28624-28630(2002).
RN [16]
RP INTERACTION WITH NCOA7.
RX PubMed=11971969; DOI=10.1128/mcb.22.10.3358-3372.2002;
RA Shao W., Halachmi S., Brown M.;
RT "ERAP140, a conserved tissue-specific nuclear receptor coactivator.";
RL Mol. Cell. Biol. 22:3358-3372(2002).
RN [17]
RP INTERACTION WITH RXRA.
RX PubMed=15509776; DOI=10.1128/mcb.24.22.9705-9725.2004;
RA Cao X., Liu W., Lin F., Li H., Kolluri S.K., Lin B., Han Y.H., Dawson M.I.,
RA Zhang X.K.;
RT "Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by
RT modulating its nuclear export and mitochondrial targeting.";
RL Mol. Cell. Biol. 24:9705-9725(2004).
RN [18]
RP INTERACTION OF THE PML-RARALPHA ONCOPROTEIN WITH UBE2I, AND SUMOYLATION.
RX PubMed=15809060; DOI=10.1016/j.bbrc.2005.03.052;
RA Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.;
RT "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for
RT localization, sumoylation, and inhibition of monocyte differentiation.";
RL Biochem. Biophys. Res. Commun. 330:746-754(2005).
RN [19]
RP INTERACTION WITH PRAME.
RX PubMed=16179254; DOI=10.1016/j.cell.2005.07.003;
RA Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R.;
RT "The human tumor antigen PRAME is a dominant repressor of retinoic acid
RT receptor signaling.";
RL Cell 122:835-847(2005).
RN [20]
RP PHOSPHORYLATION AT SER-96, FUNCTION, INTERACTION WITH AKT1, AND MUTAGENESIS
RP OF SER-95; SER-96; SER-154 AND SER-157.
RX PubMed=16417524; DOI=10.1042/bj20051794;
RA Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L., Weigel N.L.,
RA Brown P.H., Kurie J.M.;
RT "Akt phosphorylates and suppresses the transactivation of retinoic acid
RT receptor alpha.";
RL Biochem. J. 395:653-662(2006).
RN [21]
RP INTERACTION WITH ASXL1 AND NCOA1, AND MUTAGENESIS OF 409-ILE-LEU-410;
RP GLU-412; 413-MET-LEU-414 AND GLU-415.
RX PubMed=16606617; DOI=10.1074/jbc.m512616200;
RA Cho Y.S., Kim E.J., Park U.H., Sin H.S., Um S.J.;
RT "Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a
RT ligand-dependent coactivator for retinoic acid receptor.";
RL J. Biol. Chem. 281:17588-17598(2006).
RN [22]
RP INTERACTION WITH LRIF1.
RX PubMed=17455211; DOI=10.1002/jcb.21340;
RA Li H.J., Haque Z.K., Chen A., Mendelsohn M.;
RT "RIF-1, a novel nuclear receptor corepressor that associates with the
RT nuclear matrix.";
RL J. Cell. Biochem. 102:1021-1035(2007).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, SUMOYLATION AT LYS-166; LYS-171 AND
RP LYS-399, AND MUTAGENESIS OF LYS-147; LYS-166; LYS-171 AND LYS-399.
RX PubMed=19850744; DOI=10.1210/en.2009-0868;
RA Zhu L., Santos N.C., Kim K.H.;
RT "Small ubiquitin-like modifier-2 modification of retinoic acid receptor-
RT alpha regulates its subcellular localization and transcriptional
RT activity.";
RL Endocrinology 150:5586-5595(2009).
RN [24]
RP FUNCTION, DNA-BINDING, AND INDUCTION BY RETINOIC ACID.
RX PubMed=19398580; DOI=10.1128/mcb.00362-09;
RA Qin Z., Ren F., Xu X., Ren Y., Li H., Wang Y., Zhai Y., Chang Z.;
RT "ZNF536, a novel zinc finger protein specifically expressed in the brain,
RT negatively regulates neuron differentiation by repressing retinoic acid-
RT induced gene transcription.";
RL Mol. Cell. Biol. 29:3633-3643(2009).
RN [25]
RP CAUTION.
RX PubMed=19377461; DOI=10.1038/nature07954;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
RT granulopoiesis.";
RL Nature 459:455-459(2009).
RN [26]
RP RETRACTED PAPER.
RX PubMed=20078863; DOI=10.1186/1471-2199-11-3;
RA Guyot R., Vincent S., Bertin J., Samarut J., Ravel-Chapuis P.;
RT "The transforming acidic coiled coil (TACC1) protein modulates the
RT transcriptional activity of the nuclear receptors TR and RAR.";
RL BMC Mol. Biol. 11:3-3(2010).
RN [27]
RP RETRACTION NOTICE OF PUBMED:20078863.
RX PubMed=24336203; DOI=10.1038/nature12896;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "Retraction: GlcNAcylation of a histone methyltransferase in retinoic-acid-
RT induced granulopoiesis.";
RL Nature 505:574-574(2014).
RN [28]
RP PHOSPHORYLATION AT SER-219 AND SER-369, INTERACTION WITH RXRA AND PRKAR1A,
RP FUNCTION, AND MUTAGENESIS OF SER-219 AND SER-369.
RX PubMed=20215566; DOI=10.1210/en.2009-1338;
RA Santos N.C., Kim K.H.;
RT "Activity of retinoic acid receptor-alpha is directly regulated at its
RT protein kinase A sites in response to follicle-stimulating hormone
RT signaling.";
RL Endocrinology 151:2361-2372(2010).
RN [29]
RP INTERACTION WITH ACTN4.
RX PubMed=22351778; DOI=10.1074/jbc.m112.345421;
RA Khurana S., Chakraborty S., Lam M., Liu Y., Su Y.T., Zhao X., Saleem M.A.,
RA Mathieson P.W., Bruggeman L.A., Kao H.Y.;
RT "Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4
RT (ACTN4) protein mutants lose ability to activate transcription by nuclear
RT hormone receptors.";
RL J. Biol. Chem. 287:12027-12035(2012).
RN [30]
RP TISSUE SPECIFICITY, AND REPRESSION BY AGING.
RX PubMed=26463675; DOI=10.1093/brain/awv289;
RA Natrajan M.S., de la Fuente A.G., Crawford A.H., Linehan E., Nunez V.,
RA Johnson K.R., Wu T., Fitzgerald D.C., Ricote M., Bielekova B.,
RA Franklin R.J.;
RT "Retinoid X receptor activation reverses age-related deficiencies in myelin
RT debris phagocytosis and remyelination.";
RL Brain 138:3581-3597(2015).
RN [31]
RP FUNCTION, INTERACTION WITH RXRA; RXRG; HDAC3; HDAC5 AND HDAC7, SUBCELLULAR
RP LOCATION, INDUCTION BY PULSATILE SHEAR STRESS, AND ACETYLATION.
RX PubMed=28167758; DOI=10.1073/pnas.1621425114;
RA Lee D.Y., Lin T.E., Lee C.I., Zhou J., Huang Y.H., Lee P.L., Shih Y.T.,
RA Chien S., Chiu J.J.;
RT "MicroRNA-10a is crucial for endothelial response to different flow
RT patterns via interaction of retinoid acid receptors and histone
RT deacetylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:2072-2077(2017).
RN [32]
RP 9AATAD MOTIF.
RX PubMed=30468856; DOI=10.1016/j.jsbmb.2018.11.008;
RA Piskacek M., Havelka M., Jendruchova K., Knight A.;
RT "Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA
RT activation pathways.";
RL J. Steroid Biochem. Mol. Biol. 187:118-123(2019).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 82-167 IN COMPLEX WITH RXRA AND
RP DNA.
RX PubMed=10698945; DOI=10.1093/emboj/19.5.1045;
RA Rastinejad F., Wagner T., Zhao Q., Khorasanizadeh S.;
RT "Structure of the RXR-RAR DNA-binding complex on the retinoic acid response
RT element DR1.";
RL EMBO J. 19:1045-1054(2000).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 182-416 IN COMPLEX WITH M.MUSCULUS
RP RXRA.
RX PubMed=10882070; DOI=10.1016/s1097-2765(00)80424-4;
RA Bourguet W., Vivat V., Wurtz J.M., Chambon P., Gronemeyer H., Moras D.;
RT "Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding
RT domains.";
RL Mol. Cell 5:289-298(2000).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 176-421 IN COMPLEXES WITH AGONIST
RP AM580 AND NCOA1 AND WITH INVERSE AGONIST BMS493 AND NCOR1, INTERACTION WITH
RP NCOR1 AND NCOR2, AND MUTAGENESIS OF ILE-396.
RX PubMed=20543827; DOI=10.1038/nsmb.1855;
RA le Maire A., Teyssier C., Erb C., Grimaldi M., Alvarez S., de Lera A.R.,
RA Balaguer P., Gronemeyer H., Royer C.A., Germain P., Bourguet W.;
RT "A unique secondary-structure switch controls constitutive gene repression
RT by retinoic acid receptor.";
RL Nat. Struct. Mol. Biol. 17:801-807(2010).
CC -!- FUNCTION: Receptor for retinoic acid (PubMed:19850744, PubMed:16417524,
CC PubMed:20215566). Retinoic acid receptors bind as heterodimers to their
CC target response elements in response to their ligands, all-trans or 9-
CC cis retinoic acid, and regulate gene expression in various biological
CC processes (PubMed:28167758). The RXR/RAR heterodimers bind to the
CC retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3'
CC sites known as DR1-DR5 (PubMed:28167758, PubMed:19398580). In the
CC absence of ligand, the RXR-RAR heterodimers associate with a
CC multiprotein complex containing transcription corepressors that induce
CC histone deacetylation, chromatin condensation and transcriptional
CC suppression (PubMed:16417524). On ligand binding, the corepressors
CC dissociate from the receptors and associate with the coactivators
CC leading to transcriptional activation (PubMed:9267036, PubMed:19850744,
CC PubMed:20215566). Formation of a complex with histone deacetylases
CC might lead to inhibition of RARE DNA element binding and to
CC transcriptional repression (PubMed:28167758). Transcriptional
CC activation and RARE DNA element binding might be supported by the
CC transcription factor KLF2 (PubMed:28167758). RARA plays an essential
CC role in the regulation of retinoic acid-induced germ cell development
CC during spermatogenesis (By similarity). Has a role in the survival of
CC early spermatocytes at the beginning prophase of meiosis (By
CC similarity). In Sertoli cells, may promote the survival and development
CC of early meiotic prophase spermatocytes (By similarity). In concert
CC with RARG, required for skeletal growth, matrix homeostasis and growth
CC plate function (By similarity). Together with RXRA, positively
CC regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1
CC signaling response to pulsatile shear stress in vascular endothelial
CC cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7
CC corepressors, plays a role in the repression of microRNA-10a and
CC thereby promotes the inflammatory response (PubMed:28167758).
CC {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:16417524,
CC ECO:0000269|PubMed:19398580, ECO:0000269|PubMed:19850744,
CC ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:28167758,
CC ECO:0000269|PubMed:9267036}.
CC -!- SUBUNIT: Heterodimer; with RXRA (via C-terminus); association with RXRA
CC is enhanced by pulsatile shear stress (PubMed:28167758,
CC PubMed:10698945, PubMed:10882070, PubMed:20215566, PubMed:15509776).
CC Binds DNA preferentially as a heterodimer (PubMed:10698945,
CC PubMed:28167758). RXRA serves as enhancer to induce RARA binding to
CC RARE (PubMed:30468856). Interacts with RXRG (PubMed:28167758).
CC Interacts with coactivators NCOA3 and NCOA6 (PubMed:9267036,
CC PubMed:10567404). Interacts with NCOA7; the interaction requires
CC ligand-binding (PubMed:11971969). Interacts (via the ligand-binding
CC domain) with PRAME; the interaction is ligand (retinoic acid)-dependent
CC (PubMed:16179254). Interacts with AKT1; the interaction phosphorylates
CC RARA and represses transactivation (PubMed:16417524). Interacts with
CC PRKAR1A; the interaction negatively regulates RARA transcriptional
CC activity (PubMed:20215566). Interacts with NCOR1 and NCOR2
CC (PubMed:20543827). Interacts with PRMT2 (PubMed:12039952). Interacts
CC with LRIF1 (PubMed:17455211). Interacts with ASXL1 and NCOA1
CC (PubMed:16606617). Interacts with ACTN4 (PubMed:22351778). In a complex
CC with HDAC3, HDAC5 and HDAC7; the HDACs serve as corepressors of RARA,
CC causing its deacetylation and inhibition of RARE DNA element binding;
CC association with HDAC3, HDAC5 and HDAC7 is increased upon oscillatory
CC shear stress (PubMed:28167758). Interacts with CDK7 (By similarity). In
CC the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).
CC {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:10567404,
CC ECO:0000269|PubMed:10698945, ECO:0000269|PubMed:10882070,
CC ECO:0000269|PubMed:11971969, ECO:0000269|PubMed:12039952,
CC ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:16179254,
CC ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:16606617,
CC ECO:0000269|PubMed:17455211, ECO:0000269|PubMed:20078863,
CC ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:20543827,
CC ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:28167758,
CC ECO:0000269|PubMed:30468856, ECO:0000269|PubMed:9267036}.
CC -!- INTERACTION:
CC P10276; O43707-1: ACTN4; NbExp=2; IntAct=EBI-413374, EBI-15971664;
CC P10276; O15296: ALOX15B; NbExp=3; IntAct=EBI-413374, EBI-12150557;
CC P10276; Q15699: ALX1; NbExp=3; IntAct=EBI-413374, EBI-750671;
CC P10276; Q96RK4: BBS4; NbExp=3; IntAct=EBI-413374, EBI-1805814;
CC P10276; O95273: CCNDBP1; NbExp=3; IntAct=EBI-413374, EBI-748961;
CC P10276; P51946: CCNH; NbExp=2; IntAct=EBI-413374, EBI-741406;
CC P10276; Q15910: EZH2; NbExp=2; IntAct=EBI-413374, EBI-530054;
CC P10276; P50148: GNAQ; NbExp=4; IntAct=EBI-413374, EBI-3909604;
CC P10276; Q9UKP3: ITGB1BP2; NbExp=2; IntAct=EBI-413374, EBI-5659717;
CC P10276; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-413374, EBI-348259;
CC P10276; Q15648: MED1; NbExp=6; IntAct=EBI-413374, EBI-394459;
CC P10276; Q71SY5: MED25; NbExp=10; IntAct=EBI-413374, EBI-394558;
CC P10276; Q15788: NCOA1; NbExp=7; IntAct=EBI-413374, EBI-455189;
CC P10276; Q9Y6Q9: NCOA3; NbExp=2; IntAct=EBI-413374, EBI-81196;
CC P10276; O75376: NCOR1; NbExp=6; IntAct=EBI-413374, EBI-347233;
CC P10276; Q9Y618: NCOR2; NbExp=4; IntAct=EBI-413374, EBI-80830;
CC P10276; Q16236: NFE2L2; NbExp=2; IntAct=EBI-413374, EBI-2007911;
CC P10276; P13056-2: NR2C1; NbExp=3; IntAct=EBI-413374, EBI-18764867;
CC P10276; P48552: NRIP1; NbExp=4; IntAct=EBI-413374, EBI-746484;
CC P10276; Q9UPP1-2: PHF8; NbExp=2; IntAct=EBI-413374, EBI-6601215;
CC P10276; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-413374, EBI-742388;
CC P10276; P37231: PPARG; NbExp=3; IntAct=EBI-413374, EBI-781384;
CC P10276; P78527: PRKDC; NbExp=3; IntAct=EBI-413374, EBI-352053;
CC P10276; P19793: RXRA; NbExp=14; IntAct=EBI-413374, EBI-78598;
CC P10276; P28702: RXRB; NbExp=16; IntAct=EBI-413374, EBI-748576;
CC P10276; P28702-3: RXRB; NbExp=3; IntAct=EBI-413374, EBI-16429492;
CC P10276; P48443: RXRG; NbExp=18; IntAct=EBI-413374, EBI-712405;
CC P10276; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-413374, EBI-1802965;
CC P10276; P63165: SUMO1; NbExp=5; IntAct=EBI-413374, EBI-80140;
CC P10276; Q8WW24: TEKT4; NbExp=4; IntAct=EBI-413374, EBI-750487;
CC P10276; Q2M1K9: ZNF423; NbExp=2; IntAct=EBI-413374, EBI-950016;
CC P10276; Q91XC0: Ajuba; Xeno; NbExp=7; IntAct=EBI-413374, EBI-1565930;
CC P10276; P59598: Asxl1; Xeno; NbExp=4; IntAct=EBI-413374, EBI-5743705;
CC P10276-2; Q14457: BECN1; NbExp=3; IntAct=EBI-10197061, EBI-949378;
CC P10276-2; P48552: NRIP1; NbExp=3; IntAct=EBI-10197061, EBI-746484;
CC P10276-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-10197061, EBI-748974;
CC P10276-2; P28702: RXRB; NbExp=4; IntAct=EBI-10197061, EBI-748576;
CC P10276-2; P48443: RXRG; NbExp=6; IntAct=EBI-10197061, EBI-712405;
CC P10276-2; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-10197061, EBI-750487;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19850744,
CC ECO:0000269|PubMed:28167758}. Cytoplasm {ECO:0000269|PubMed:19850744,
CC ECO:0000269|PubMed:28167758}. Note=Nuclear localization depends on
CC ligand binding, phosphorylation and sumoylation (PubMed:19850744).
CC Translocation to the nucleus in the absence of ligand is dependent on
CC activation of PKC and the downstream MAPK phosphorylation (By
CC similarity). Increased nuclear localization upon pulsatile shear stress
CC (PubMed:28167758). {ECO:0000250|UniProtKB:P11416,
CC ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:28167758}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Alpha-1;
CC IsoId=P10276-1; Sequence=Displayed;
CC Name=Alpha-2;
CC IsoId=P10276-2; Sequence=VSP_003629;
CC Name=Alpha-1-deltaBC;
CC IsoId=P10276-3; Sequence=VSP_043143;
CC -!- TISSUE SPECIFICITY: Expressed in monocytes.
CC {ECO:0000269|PubMed:26463675}.
CC -!- INDUCTION: Expression is induced ba retinoic acid (PubMed:19398580).
CC Down-regulated by aging (PubMed:26463675). Induced by pulsatile shear
CC stress (PubMed:28167758). {ECO:0000269|PubMed:19398580,
CC ECO:0000269|PubMed:26463675, ECO:0000269|PubMed:28167758}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000305|PubMed:30468856}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Phosphorylation
CC does not change during cell cycle. Phosphorylation on Ser-77 is crucial
CC for transcriptional activity (By similarity). Phosphorylation by AKT1
CC is required for the repressor activity but has no effect on DNA
CC binding, protein stability nor subcellular localization. Phosphorylated
CC by PKA in vitro. This phosphorylation on Ser-219 and Ser-369 is
CC critical for ligand binding, nuclear localization and transcriptional
CC activity in response to FSH signaling. {ECO:0000250,
CC ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:20215566}.
CC -!- PTM: Sumoylated with SUMO2, mainly on Lys-399 which is also required
CC for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a
CC confromational change may occur that allows sumoylation on two
CC additional site, Lys-166 and Lys-171. Probably desumoylated by SENP6.
CC Sumoylation levels determine nuclear localization and regulate ATRA-
CC mediated transcriptional activity. {ECO:0000269|PubMed:15809060,
CC ECO:0000269|PubMed:19850744}.
CC -!- PTM: Trimethylation enhances heterodimerization with RXRA and
CC positively modulates the transcriptional activation.
CC -!- PTM: Ubiquitinated.
CC -!- PTM: Acetylated; acetylation is increased upon pulsatile shear stress
CC and decreased upon oscillatory shear stress.
CC {ECO:0000269|PubMed:28167758}.
CC -!- DISEASE: Note=Chromosomal aberrations involving RARA are commonly found
CC in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with
CC ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation
CC t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the
CC PML ring structure and coiled-coil domain for both interaction with
CC UBE2I, nuclear microspeckle location and sumoylation. In addition, the
CC coiled-coil domain functions in blocking RA-mediated transactivation
CC and cell differentiation. {ECO:0000269|PubMed:12691149,
CC ECO:0000269|PubMed:8302850, ECO:0000269|PubMed:8562957}.
CC -!- MISCELLANEOUS: [Isoform Alpha-1-deltaBC]: Does not bind nor
CC transactivate RARE on its own but may do so as a heterodimer with
CC Alpha-1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be part of the MLL5-L complex, at
CC least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and
CC OGT (PubMed:19377461). However, the corresponding article has been
CC retracted (PubMed:24336203). {ECO:0000269|PubMed:19377461,
CC ECO:0000269|PubMed:24336203}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB00112.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB00113.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB62809.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/46/RARA";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Retinoic acid receptor entry;
CC URL="https://en.wikipedia.org/wiki/Retinoic_acid_receptor";
CC ---------------------------------------------------------------------------
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DR EMBL; X06614; CAA29829.1; -; mRNA.
DR EMBL; X06538; CAA29787.1; -; mRNA.
DR EMBL; AF088895; AAD05222.1; -; Genomic_DNA.
DR EMBL; AF088889; AAD05222.1; JOINED; Genomic_DNA.
DR EMBL; AF088890; AAD05222.1; JOINED; Genomic_DNA.
DR EMBL; AF088891; AAD05222.1; JOINED; Genomic_DNA.
DR EMBL; AF088892; AAD05222.1; JOINED; Genomic_DNA.
DR EMBL; AF088893; AAD05222.1; JOINED; Genomic_DNA.
DR EMBL; AF088894; AAD05222.1; JOINED; Genomic_DNA.
DR EMBL; FJ487576; ACK86665.1; -; mRNA.
DR EMBL; AC080112; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008727; AAH08727.1; -; mRNA.
DR EMBL; BC071733; AAH71733.1; -; mRNA.
DR EMBL; X56058; CAA39533.1; -; Genomic_DNA.
DR EMBL; X58685; CAA39533.1; JOINED; mRNA.
DR EMBL; X58685; CAA41532.1; -; mRNA.
DR EMBL; U41742; AAB00112.1; ALT_INIT; mRNA.
DR EMBL; U41743; AAB00113.1; ALT_INIT; mRNA.
DR EMBL; AF283809; AAF87249.1; -; Genomic_DNA.
DR EMBL; AB067754; BAB62809.1; ALT_INIT; mRNA.
DR CCDS; CCDS11366.1; -. [P10276-1]
DR CCDS; CCDS42317.1; -. [P10276-2]
DR CCDS; CCDS45671.1; -. [P10276-3]
DR PIR; A29491; A29491.
DR RefSeq; NP_000955.1; NM_000964.3. [P10276-1]
DR RefSeq; NP_001019980.1; NM_001024809.3. [P10276-2]
DR RefSeq; NP_001138773.1; NM_001145301.2. [P10276-1]
DR RefSeq; NP_001138774.1; NM_001145302.2. [P10276-3]
DR RefSeq; XP_005257610.1; XM_005257553.1. [P10276-1]
DR RefSeq; XP_005257611.1; XM_005257554.1. [P10276-1]
DR RefSeq; XP_011523397.1; XM_011525095.1. [P10276-1]
DR PDB; 1DKF; X-ray; 2.50 A; B=182-416.
DR PDB; 1DSZ; X-ray; 1.70 A; A=82-167.
DR PDB; 3A9E; X-ray; 2.75 A; B=153-421.
DR PDB; 3KMR; X-ray; 1.80 A; A=176-421.
DR PDB; 3KMZ; X-ray; 2.10 A; A/B=176-421.
DR PDB; 4DQM; X-ray; 2.75 A; A/C=182-415.
DR PDB; 5K13; X-ray; 1.85 A; A=181-426.
DR PDB; 6XWG; X-ray; 2.40 A; D=82-167.
DR PDB; 7AOS; X-ray; 2.55 A; B=176-421.
DR PDB; 7APO; X-ray; 2.40 A; A/B=176-421.
DR PDB; 7QAA; X-ray; 2.76 A; B=182-416.
DR PDB; 7WQQ; X-ray; 1.90 A; A=176-421.
DR PDBsum; 1DKF; -.
DR PDBsum; 1DSZ; -.
DR PDBsum; 3A9E; -.
DR PDBsum; 3KMR; -.
DR PDBsum; 3KMZ; -.
DR PDBsum; 4DQM; -.
DR PDBsum; 5K13; -.
DR PDBsum; 6XWG; -.
DR PDBsum; 7AOS; -.
DR PDBsum; 7APO; -.
DR PDBsum; 7QAA; -.
DR PDBsum; 7WQQ; -.
DR AlphaFoldDB; P10276; -.
DR EMDB; EMD-17542; -.
DR SASBDB; P10276; -.
DR SMR; P10276; -.
DR BioGRID; 111849; 163.
DR ComplexPortal; CPX-508; RXRalpha-RARalpha retinoic acid receptor complex.
DR ComplexPortal; CPX-525; RARalpha-NCOA1 activated retinoic acid receptor complex.
DR ComplexPortal; CPX-666; RARalpha-NCOA2 activated retinoic acid receptor complex.
DR ComplexPortal; CPX-816; RXRalpha-RARalpha-NCOA2 retinoic acid receptor complex.
DR CORUM; P10276; -.
DR DIP; DIP-34N; -.
DR IntAct; P10276; 74.
DR MINT; P10276; -.
DR STRING; 9606.ENSP00000254066; -.
DR BindingDB; P10276; -.
DR ChEMBL; CHEMBL2055; -.
DR DrugBank; DB00459; Acitretin.
DR DrugBank; DB00210; Adapalene.
DR DrugBank; DB00523; Alitretinoin.
DR DrugBank; DB00926; Etretinate.
DR DrugBank; DB00982; Isotretinoin.
DR DrugBank; DB05785; LGD-1550.
DR DrugBank; DB04942; Tamibarotene.
DR DrugBank; DB00799; Tazarotene.
DR DrugBank; DB00755; Tretinoin.
DR DrugBank; DB12808; Trifarotene.
DR DrugCentral; P10276; -.
DR GuidetoPHARMACOLOGY; 590; -.
DR MoonDB; P10276; Predicted.
DR iPTMnet; P10276; -.
DR PhosphoSitePlus; P10276; -.
DR SwissPalm; P10276; -.
DR BioMuta; RARA; -.
DR DMDM; 133483; -.
DR EPD; P10276; -.
DR jPOST; P10276; -.
DR MassIVE; P10276; -.
DR MaxQB; P10276; -.
DR PaxDb; 9606-ENSP00000254066; -.
DR PeptideAtlas; P10276; -.
DR ProteomicsDB; 52592; -. [P10276-1]
DR ProteomicsDB; 52593; -. [P10276-2]
DR ProteomicsDB; 52594; -. [P10276-3]
DR Antibodypedia; 16473; 923 antibodies from 47 providers.
DR DNASU; 5914; -.
DR Ensembl; ENST00000254066.10; ENSP00000254066.5; ENSG00000131759.18. [P10276-1]
DR Ensembl; ENST00000394081.7; ENSP00000377643.3; ENSG00000131759.18. [P10276-2]
DR Ensembl; ENST00000394089.6; ENSP00000377649.2; ENSG00000131759.18. [P10276-1]
DR Ensembl; ENST00000425707.7; ENSP00000389993.3; ENSG00000131759.18. [P10276-3]
DR GeneID; 5914; -.
DR KEGG; hsa:5914; -.
DR MANE-Select; ENST00000254066.10; ENSP00000254066.5; NM_000964.4; NP_000955.1.
DR UCSC; uc002hun.3; human. [P10276-1]
DR AGR; HGNC:9864; -.
DR CTD; 5914; -.
DR DisGeNET; 5914; -.
DR GeneCards; RARA; -.
DR HGNC; HGNC:9864; RARA.
DR HPA; ENSG00000131759; Low tissue specificity.
DR MalaCards; RARA; -.
DR MIM; 180240; gene.
DR MIM; 612376; phenotype.
DR neXtProt; NX_P10276; -.
DR OpenTargets; ENSG00000131759; -.
DR Orphanet; 520; Acute promyelocytic leukemia.
DR PharmGKB; PA34225; -.
DR VEuPathDB; HostDB:ENSG00000131759; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159997; -.
DR HOGENOM; CLU_007368_18_2_1; -.
DR InParanoid; P10276; -.
DR OMA; CHTRAPT; -.
DR OrthoDB; 5390715at2759; -.
DR PhylomeDB; P10276; -.
DR TreeFam; TF328382; -.
DR PathwayCommons; P10276; -.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-HSA-5362517; Signaling by Retinoic Acid.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis.
DR SignaLink; P10276; -.
DR SIGNOR; P10276; -.
DR BioGRID-ORCS; 5914; 30 hits in 1195 CRISPR screens.
DR ChiTaRS; RARA; human.
DR EvolutionaryTrace; P10276; -.
DR GeneWiki; Retinoic_acid_receptor_alpha; -.
DR GenomeRNAi; 5914; -.
DR Pharos; P10276; Tclin.
DR PRO; PR:P10276; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P10276; Protein.
DR Bgee; ENSG00000131759; Expressed in mammary duct and 192 other cell types or tissues.
DR ExpressionAtlas; P10276; baseline and differential.
DR Genevisible; P10276; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0051393; F:alpha-actinin binding; IPI:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IMP:ARUK-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:1901363; F:heterocyclic compound binding; IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IEA:Ensembl.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:ARUK-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0051018; F:protein kinase A binding; IDA:UniProtKB.
DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB.
DR GO; GO:0001972; F:retinoic acid binding; IDA:BHF-UCL.
DR GO; GO:0044323; F:retinoic acid-responsive element binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:ARUK-UCL.
DR GO; GO:0060591; P:chondroblast differentiation; IEA:Ensembl.
DR GO; GO:0031076; P:embryonic camera-type eye development; IEA:Ensembl.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0002068; P:glandular epithelial cell development; IEA:Ensembl.
DR GO; GO:0003417; P:growth plate cartilage development; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0060173; P:limb development; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0061037; P:negative regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:UniProtKB.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:ARUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0032689; P:negative regulation of type II interferon production; IDA:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0051099; P:positive regulation of binding; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IDA:BHF-UCL.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:BHF-UCL.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; IDA:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0031641; P:regulation of myelination; IEA:Ensembl.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0060010; P:Sertoli cell fate commitment; IEA:Ensembl.
DR GO; GO:0060534; P:trachea cartilage development; IEA:Ensembl.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; IEA:Ensembl.
DR CDD; cd06964; NR_DBD_RAR; 1.
DR CDD; cd06937; NR_LBD_RAR; 1.
DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR Gene3D; 1.10.565.10; Retinoid X Receptor; 1.
DR IDEAL; IID00365; -.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR047159; NR_DBD_RAR.
DR InterPro; IPR047158; NR_LBD_RAR.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR003078; Retinoic_acid_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR24085; NUCLEAR HORMONE RECEPTOR; 1.
DR PANTHER; PTHR24085:SF8; RETINOIC ACID RECEPTOR ALPHA; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01292; RETNOICACIDR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosomal rearrangement; Cytoplasm;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Proto-oncogene; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..462
FT /note="Retinoic acid receptor alpha"
FT /id="PRO_0000053461"
FT DOMAIN 183..417
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 88..153
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 88..108
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 124..148
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..87
FT /note="Modulating"
FT REGION 52..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..182
FT /note="Hinge"
FT REGION 404..419
FT /note="Required for binding corepressor NCOR1"
FT REGION 419..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 408..416
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:30468856"
FT COMPBIAS 52..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 60..61
FT /note="Breakpoint for translocation to form PLZF-RAR-alpha,
FT RAR-alpha1-PLZF and PML-RAR-alpha oncogenes"
FT MOD_RES 77
FT /note="Phosphoserine; by CDK7"
FT /evidence="ECO:0000250|UniProtKB:P11416"
FT MOD_RES 96
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:16417524"
FT MOD_RES 219
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:20215566"
FT MOD_RES 369
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:20215566"
FT CROSSLNK 166
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19850744"
FT CROSSLNK 171
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19850744"
FT CROSSLNK 399
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19850744"
FT VAR_SEQ 1..60
FT /note="MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSG
FT YSTPSPAT -> MYESVEVGGPTPNPFLVVDFYNQNRACLLPEKGLPAPGPYSTPLRTP
FT LWNGSNHS (in isoform Alpha-2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003629"
FT VAR_SEQ 61..157
FT /note="Missing (in isoform Alpha-1-deltaBC)"
FT /evidence="ECO:0000303|PubMed:11812818"
FT /id="VSP_043143"
FT MUTAGEN 95
FT /note="S->A: No effect on PKB/AKT1-mediated
FT phosphorylation. Repressed transactivation."
FT /evidence="ECO:0000269|PubMed:16417524"
FT MUTAGEN 96
FT /note="S->A: Abolishes PKB/AKT1-mediated phosphorylation.
FT Repressed transactivation."
FT /evidence="ECO:0000269|PubMed:16417524"
FT MUTAGEN 147
FT /note="K->R: Abrogates sumoylation in the presence or
FT absence of ATRA and primarily nuclear localization and
FT enhanced ATRA-mediated transcriptional activity; when
FT associated with R-166; R-171 and R-399."
FT /evidence="ECO:0000269|PubMed:19850744"
FT MUTAGEN 154
FT /note="S->A: No effect on PKB/AKT1-mediated
FT phosphorylation. No repression of transactivation."
FT /evidence="ECO:0000269|PubMed:16417524"
FT MUTAGEN 157
FT /note="S->A: No effect on PKB/AKT1-mediated
FT phosphorylation. Repressed transactivation."
FT /evidence="ECO:0000269|PubMed:16417524"
FT MUTAGEN 166
FT /note="K->R: Cytoplasmic in the absence of ATRA and reduced
FT transcriptional activity in the presence of ATRA. Low
FT sumoylation levels in the presence of ATRA; when associated
FT with R-399. Nuclear localization and enhanced
FT transcriptional activity; when associated with R-171 and R-
FT 399. Primarily nuclear localization and enhanced ATRA-
FT mediated transcriptional activity; when associated with R-
FT 147; R-171 and R-399."
FT /evidence="ECO:0000269|PubMed:19850744"
FT MUTAGEN 171
FT /note="K->R: Cytoplasmic in the absence of ATRA and reduced
FT transcriptional activity in the presence of ATRA. Low
FT sumoylation levels in the presence of ATRA; when associated
FT with R-399. Nuclear localization and enhanced
FT transcriptional activity; when associated with R-166 and R-
FT 399. Primarily nuclear localization and enhanced ATRA-
FT mediated transcriptional activity; when associated with R-
FT 147; R-166 and R-399."
FT /evidence="ECO:0000269|PubMed:19850744"
FT MUTAGEN 219
FT /note="S->A: No effect on heterodimerization with RARA. On
FT ATRA treatment, localizes to the nucleus, and increased
FT protein levels; when associated with A-369."
FT /evidence="ECO:0000269|PubMed:20215566"
FT MUTAGEN 219
FT /note="S->E: No effect on heterodimerization with RARA. On
FT ATRA treatment, localizes to both nucleus and cytoplasm, no
FT increase in protein levels, and decrease in RARA-mediated
FT transcriptional activity; when associated with E-369."
FT /evidence="ECO:0000269|PubMed:20215566"
FT MUTAGEN 369
FT /note="S->A: No effect on heterodimerization with RARA. On
FT ATRA treatment, localizes to the nucleus, and increased
FT protein levels; when associated with A-219."
FT /evidence="ECO:0000269|PubMed:20215566"
FT MUTAGEN 369
FT /note="S->E: Some inhibition of heterodimerization with
FT RARA. On ATRA treatment, localizes to both nucleus and
FT cytoplasm, increase in protein levels, and decrease in
FT RARA-mediated transcriptional activity; when associated
FT with E-219."
FT /evidence="ECO:0000269|PubMed:20215566"
FT MUTAGEN 396
FT /note="I->E: Abrogates interaction with NCOR1 or NCOR2.
FT Increased affinity for NCOR1 and NCOR2 in the presence of
FT BMS493. Increased transcriptional activity in the presence
FT of agonist and decreased activity in the presence of
FT neutral antagonist."
FT /evidence="ECO:0000269|PubMed:20543827"
FT MUTAGEN 399
FT /note="K->R: In the absence of ATRA, abolishes sumoylation
FT and is mainly nuclear. In the presence of ATRA, some
FT sumoylation, cytoplasmic location, reduced transcriptional
FT activity and no SENP6 binding. Low sumoylation levels in
FT the presence of ATRA and nuclear location in the absence of
FT ATRA; when associated with R-166 or with R-171. Primarily
FT nuclear localization and enhanced ATRA-mediated
FT transcriptional activity; when associated with R-147; R-166
FT and R-171."
FT /evidence="ECO:0000269|PubMed:19850744"
FT MUTAGEN 409..410
FT /note="LI->AA: Abolishes interaction with ASXL1 and NCOA1."
FT /evidence="ECO:0000269|PubMed:16606617"
FT MUTAGEN 412
FT /note="E->Q: Impairs interaction with ASXL1 and NCOA1; when
FT associated with Q-415."
FT /evidence="ECO:0000269|PubMed:16606617"
FT MUTAGEN 413..414
FT /note="ML->AA: Abolishes interaction with ASXL1 and NCOA1."
FT /evidence="ECO:0000269|PubMed:16606617"
FT MUTAGEN 415
FT /note="E->Q: Impairs interaction with ASXL1 and NCOA1; when
FT associated with Q-412."
FT /evidence="ECO:0000269|PubMed:16606617"
FT CONFLICT 241
FT /note="E -> D (in Ref. 3; AAD05222)"
FT /evidence="ECO:0000305"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1DSZ"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1DSZ"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:6XWG"
FT HELIX 106..117
FT /evidence="ECO:0007829|PDB:1DSZ"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1DSZ"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1DSZ"
FT HELIX 141..150
FT /evidence="ECO:0007829|PDB:1DSZ"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:1DSZ"
FT HELIX 183..196
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:3KMR"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:5K13"
FT HELIX 222..244
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 254..275
FT /evidence="ECO:0007829|PDB:3KMR"
FT TURN 279..282
FT /evidence="ECO:0007829|PDB:3KMR"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:3KMR"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 294..300
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 306..316
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 323..334
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 345..366
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 373..401
FT /evidence="ECO:0007829|PDB:3KMR"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:3KMR"
FT HELIX 408..414
FT /evidence="ECO:0007829|PDB:3KMR"
SQ SEQUENCE 462 AA; 50771 MW; E8D1CF9A1E57CB99 CRC64;
MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV SGYSTPSPAT
IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM
VYTCHRDKNC IINKVTRNRC QYCRLQKCFE VGMSKESVRN DRNKKKKEVP KPECSESYTL
TPEVGELIEK VRKAHQETFP ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV
EFAKQLPGFT TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA
GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDRVDM LQEPLLEALK
VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGL
DTLSGQPGGG GRDGGGLAPP PGSCSPSLSP SSNRSSPATH SP
//
