GenomeNet

Database: UniProt
Entry: P10276
LinkDB: P10276
Original site: P10276 
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   07-APR-2021, entry version 252.
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   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   [25]
RP   INTERACTION WITH TACC1.
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   [26]
RP   CAUTION, AND 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   [27]
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   [28]
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   [29]
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   [30]
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   [31]
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   [32]
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   [33]
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   [34]
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). In the absence of ligand, the
CC       RXR-RAR heterodimers associate with a multiprotein complex containing
CC       transcription corepressors that induce histone deacetylation, chromatin
CC       condensation and transcriptional suppression (PubMed:16417524). On
CC       ligand binding, the corepressors dissociate from the receptors and
CC       associate with the coactivators leading to transcriptional activation
CC       (PubMed:9267036, PubMed:19850744, PubMed:20215566). Formation of a
CC       complex with histone deacetylases might lead to inhibition of RARE DNA
CC       element binding and to transcriptional repression (PubMed:28167758).
CC       Transcriptional activation and RARE DNA element binding might be
CC       supported by the transcription factor KLF2 (PubMed:28167758). RARA
CC       plays an essential role in the regulation of retinoic acid-induced germ
CC       cell development during spermatogenesis (By similarity). Has a role in
CC       the survival of early spermatocytes at the beginning prophase of
CC       meiosis (By similarity). In Sertoli cells, may promote the survival and
CC       development of early meiotic prophase spermatocytes (By similarity). In
CC       concert with RARG, required for skeletal growth, matrix homeostasis and
CC       growth 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:19850744, ECO:0000269|PubMed:20215566,
CC       ECO:0000269|PubMed:28167758, 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=15; IntAct=EBI-413374, EBI-748576;
CC       P10276; P28702-3: RXRB; NbExp=3; IntAct=EBI-413374, EBI-16429492;
CC       P10276; P48443: RXRG; NbExp=17; 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: Down-regulated by aging (PubMed:26463675). Induced by
CC       pulsatile shear stress (PubMed:28167758). {ECO:0000269|PubMed:26463675,
CC       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; Evidence={ECO:0000305};
CC       Sequence=AAB00113.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=BAB62809.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/RARAID46.html";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Retinoic acid receptor entry;
CC       URL="https://en.wikipedia.org/wiki/Retinoic_acid_receptor";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   PDBsum; 1DKF; -.
DR   PDBsum; 1DSZ; -.
DR   PDBsum; 3A9E; -.
DR   PDBsum; 3KMR; -.
DR   PDBsum; 3KMZ; -.
DR   PDBsum; 4DQM; -.
DR   PDBsum; 5K13; -.
DR   PDBsum; 6XWG; -.
DR   SASBDB; P10276; -.
DR   SMR; P10276; -.
DR   BioGRID; 111849; 159.
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; 73.
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   jPOST; P10276; -.
DR   MassIVE; P10276; -.
DR   PaxDb; P10276; -.
DR   PeptideAtlas; P10276; -.
DR   PRIDE; P10276; -.
DR   ProteomicsDB; 52592; -. [P10276-1]
DR   ProteomicsDB; 52593; -. [P10276-2]
DR   ProteomicsDB; 52594; -. [P10276-3]
DR   Antibodypedia; 16473; 783 antibodies.
DR   DNASU; 5914; -.
DR   Ensembl; ENST00000254066; ENSP00000254066; ENSG00000131759. [P10276-1]
DR   Ensembl; ENST00000394081; ENSP00000377643; ENSG00000131759. [P10276-2]
DR   Ensembl; ENST00000394089; ENSP00000377649; ENSG00000131759. [P10276-1]
DR   Ensembl; ENST00000425707; ENSP00000389993; ENSG00000131759. [P10276-3]
DR   GeneID; 5914; -.
DR   KEGG; hsa:5914; -.
DR   UCSC; uc002hun.3; human. [P10276-1]
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:ENSG00000131759.17; -.
DR   eggNOG; KOG3575; Eukaryota.
DR   GeneTree; ENSGT00940000159997; -.
DR   HOGENOM; CLU_007368_18_2_1; -.
DR   InParanoid; P10276; -.
DR   OMA; AECSESY; -.
DR   OrthoDB; 1165737at2759; -.
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; 17 hits in 1020 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 nasal cavity epithelium and 232 other tissues.
DR   ExpressionAtlas; P10276; baseline and differential.
DR   Genevisible; P10276; HS.
DR   GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR   GO; GO:0009986; C:cell surface; IC:BHF-UCL.
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:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
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:0019899; F:enzyme binding; IPI:UniProtKB.
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:0008134; F:transcription factor 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:0030851; P:granulocyte differentiation; TAS:Reactome.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:UniProtKB.
DR   GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:BHF-UCL.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
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: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: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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0032526; P:response to retinoic acid; IMP:BHF-UCL.
DR   GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; IDA:BHF-UCL.
DR   GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
DR   Gene3D; 1.10.565.10; -; 1.
DR   Gene3D; 3.30.50.10; -; 1.
DR   IDEAL; IID00365; -.
DR   InterPro; IPR035500; NHR-like_dom_sf.
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   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; SSF48508; SSF48508; 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          154..182
FT                   /note="Hinge"
FT   REGION          404..419
FT                   /note="Required for binding corepressor NCOR1"
FT   MOTIF           408..416
FT                   /note="9aaTAD"
FT                   /evidence="ECO:0000269|PubMed:30468856"
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:0007744|PDB:1DSZ"
FT   STRAND          97..99
FT                   /evidence="ECO:0007744|PDB:1DSZ"
FT   HELIX           106..117
FT                   /evidence="ECO:0007744|PDB:1DSZ"
FT   TURN            134..136
FT                   /evidence="ECO:0007744|PDB:1DSZ"
FT   HELIX           137..139
FT                   /evidence="ECO:0007744|PDB:1DSZ"
FT   HELIX           141..150
FT                   /evidence="ECO:0007744|PDB:1DSZ"
FT   HELIX           155..157
FT                   /evidence="ECO:0007744|PDB:1DSZ"
FT   HELIX           183..196
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           202..204
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   STRAND          214..216
FT                   /evidence="ECO:0007744|PDB:5K13"
FT   HELIX           222..244
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           249..251
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           254..275
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   TURN            279..282
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   STRAND          283..285
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   STRAND          289..293
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           294..300
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           303..305
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           306..316
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           317..319
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           323..334
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           345..366
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           373..401
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   STRAND          402..404
FT                   /evidence="ECO:0007744|PDB:3KMR"
FT   HELIX           408..414
FT                   /evidence="ECO:0007744|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
//
DBGET integrated database retrieval system