RARA_MOUSE
ID RARA_MOUSE Reviewed; 462 AA.
AC P11416; P22603;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 229.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
RX PubMed=2544807; DOI=10.1038/339714a0;
RA Zelent A., Krust A., Petkovich M., Kastner P., Chambon P.;
RT "Cloning of murine alpha and beta retinoic acid receptors and a novel
RT receptor gamma predominantly expressed in skin.";
RL Nature 339:714-717(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
RX PubMed=8383767; DOI=10.3109/10799899309073687;
RA Heiermann R., Rentrop M., Lang E., Maelicke A.;
RT "Cloning of several genes coding for retinoic acid nuclear receptors in the
RT mouse embryonal carcinoma cell line PCC7-MZ1.";
RL J. Recept. Res. 13:693-709(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
RX PubMed=1846598; DOI=10.1002/j.1460-2075.1991.tb07921.x;
RA Leroy P., Krust A., Zelent A., Mendelsohn C., Garnier J.-M., Kastner P.,
RA Dierich A., Chambon P.;
RT "Multiple isoforms of the mouse retinoic acid receptor alpha are generated
RT by alternative splicing and differential induction by retinoic acid.";
RL EMBO J. 10:59-69(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (VARIANT IN EMBRYONAL CARCINOMA CELL LINE
RP RAC65).
RX PubMed=1320576; DOI=10.1111/j.1432-0436.1992.tb00766.x;
RA Kruyt F.A.E., van der Veer L., Mader S., van den Brink C.E., Feijen A.,
RA Jonk L.J., Kruijer W., van der Saag P.T.;
RT "Retinoic acid resistance of the variant embryonal carcinoma cell line
RT RAC65 is caused by expression of a truncated RAR alpha.";
RL Differentiation 49:27-37(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (VARIANT IN EMBRYONAL CARCINOMA CELL LINE
RP RAC65).
RX PubMed=2174108; DOI=10.1128/mcb.10.12.6445-6453.1990;
RA Pratt M.A.C., Kralova J., McBurney M.W.;
RT "A dominant negative mutation of the alpha retinoic acid receptor gene in a
RT retinoic acid-nonresponsive embryonal carcinoma cell.";
RL Mol. Cell. Biol. 10:6445-6453(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 PROTEIN SEQUENCE OF 340-359, METHYLATION AT LYS-347, FUNCTION, INTERACTION
RP WITH RXRA AND NCOR1, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS
RP OF LYS-347.
RX PubMed=17205979; DOI=10.1074/mcp.m600223-mcp200;
RA Huq M.D., Tsai N.-P., Khan S.A., Wei L.-N.;
RT "Lysine trimethylation of retinoic acid receptor-alpha: a novel means to
RT regulate receptor function.";
RL Mol. Cell. Proteomics 6:677-688(2007).
RN [8]
RP INTERACTION WITH CDK7 AND GTF2H3, PHOSPHORYLATION AT SER-77, FUNCTION, AND
RP MUTAGENESIS OF SER-74; SER-77; SER-449; SER-456 AND SER-461.
RX PubMed=9230306; DOI=10.1016/s0092-8674(00)80317-7;
RA Rochette-Egly C., Adam S., Rossignol M., Egly J.-M., Chambon P.;
RT "Stimulation of RAR alpha activation function AF-1 through binding to the
RT general transcription factor TFIIH and phosphorylation by CDK7.";
RL Cell 90:97-107(1997).
RN [9]
RP INTERACTION WITH NCOA3.
RX PubMed=9192892; DOI=10.1038/42652;
RA Torchia J., Rose D.W., Inostroza J., Kamei Y., Westin S., Glass C.K.,
RA Rosenfeld M.G.;
RT "The transcriptional co-activator p/CIP binds CBP and mediates nuclear-
RT receptor function.";
RL Nature 387:677-684(1997).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10660575; DOI=10.1074/jbc.275.6.4145;
RA Braun K.W., Tribley W.A., Griswold M.D., Kim K.H.;
RT "Follicle-stimulating hormone inhibits all-trans-retinoic acid-induced
RT retinoic acid receptor alpha nuclear localization and transcriptional
RT activation in mouse Sertoli cell lines.";
RL J. Biol. Chem. 275:4145-4151(2000).
RN [11]
RP INTERACTION WITH NCOA6.
RX PubMed=10788465; DOI=10.1074/jbc.275.18.13510;
RA Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K.;
RT "Isolation and characterization of peroxisome proliferator-activated
RT receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR.";
RL J. Biol. Chem. 275:13510-13516(2000).
RN [12]
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12079996; DOI=10.1095/biolreprod67.1.29;
RA Braun K.W., Vo M.N., Kim K.H.;
RT "Positive regulation of retinoic acid receptor alpha by protein kinase C
RT and mitogen-activated protein kinase in sertoli cells.";
RL Biol. Reprod. 67:29-37(2002).
RN [13]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=15901285; DOI=10.1111/j.1432-0436.2005.00018.x;
RA Chung S.S., Wang X., Wolgemuth D.J.;
RT "Male sterility in mice lacking retinoic acid receptor alpha involves
RT specific abnormalities in spermiogenesis.";
RL Differentiation 73:188-198(2005).
RN [14]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=17905941; DOI=10.1196/annals.1411.008;
RA Doyle T.J., Braun K.W., McLean D.J., Wright R.W., Griswold M.D., Kim K.H.;
RT "Potential functions of retinoic acid receptor A in Sertoli cells and germ
RT cells during spermatogenesis.";
RL Ann. N. Y. Acad. Sci. 1120:114-130(2007).
RN [15]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19389355; DOI=10.1016/j.ydbio.2009.01.031;
RA Williams J.A., Kondo N., Okabe T., Takeshita N., Pilchak D.M., Koyama E.,
RA Ochiai T., Jensen D., Chu M.L., Kane M.A., Napoli J.L., Enomoto-Iwamoto M.,
RA Ghyselinck N., Chambon P., Pacifici M., Iwamoto M.;
RT "Retinoic acid receptors are required for skeletal growth, matrix
RT homeostasis and growth plate function in postnatal mouse.";
RL Dev. Biol. 328:315-327(2009).
RN [16]
RP PHOSPHORYLATION AT SER-77 AND SER-369, FUNCTION, INTERACTION WITH GTF2H3,
RP AND MUTAGENESIS OF SER-77 AND SER-369.
RX PubMed=19078967; DOI=10.1038/emboj.2008.256;
RA Bruck N., Vitoux D., Ferry C., Duong V., Bauer A., de The H.,
RA Rochette-Egly C.;
RT "A coordinated phosphorylation cascade initiated by p38MAPK/MSK1 directs
RT RARalpha to target promoters.";
RL EMBO J. 28:34-47(2009).
RN [17]
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).
CC -!- FUNCTION: Receptor for retinoic acid (PubMed:17205979). Retinoic acid
CC receptors bind as heterodimers to their target response elements in
CC response to their ligands, all-trans or 9-cis retinoic acid, and
CC regulate gene expression in various biological processes
CC (PubMed:17205979). The RXR/RAR heterodimers bind to the retinoic acid
CC response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as
CC DR1-DR5 (PubMed:17205979). In the absence of ligand, the RXR-RAR
CC heterodimers associate with a multiprotein complex containing
CC transcription corepressors that induce histone deacetylation, chromatin
CC condensation and transcriptional suppression (By similarity). On ligand
CC binding, the corepressors dissociate from the receptors and associate
CC with the coactivators leading to transcriptional activation
CC (PubMed:17205979, PubMed:9230306, PubMed:19078967). Formation of
CC heterocomplex with histone deacetylases might lead to inhibition of
CC RARE DNA element binding and to transcriptional repression (By
CC similarity). Transcriptional activation and RARE DNA element binding
CC might be supported by the transcription factor KLF2 (By similarity).
CC RARA plays an essential role in the regulation of retinoic acid-induced
CC germ cell development during spermatogenesis (PubMed:15901285). Has a
CC role in the survival of early spermatocytes at the beginning prophase
CC of meiosis (PubMed:15901285, PubMed:17905941). In Sertoli cells, may
CC promote the survival and development of early meiotic prophase
CC spermatocytes (PubMed:10660575, PubMed:17905941). In concert with RARG,
CC required for skeletal growth, matrix homeostasis and growth plate
CC function (PubMed:19389355). Together with RXRA, positively regulates
CC microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling
CC response to pulsatile shear stress in vascular endothelial cells (By
CC similarity). In association with HDAC3, HDAC5 and HDAC7 corepressors,
CC plays a role in the repression of microRNA-10a and thereby promotes the
CC inflammatory response (By similarity). {ECO:0000250|UniProtKB:P10276,
CC ECO:0000269|PubMed:10660575, ECO:0000269|PubMed:15901285,
CC ECO:0000269|PubMed:17205979, ECO:0000269|PubMed:17905941,
CC ECO:0000269|PubMed:19078967, ECO:0000269|PubMed:19389355,
CC ECO:0000269|PubMed:9230306}.
CC -!- SUBUNIT: Heterodimer; with RXRA (PubMed:17205979). Binds DNA
CC preferentially as a heterodimer (By similarity). RXRA serves as
CC enhancer to induce RARA binding to RARE (By similarity). Interacts with
CC RXRG (By similarity). Interacts with NCOA3 and NCOA6 coactivators,
CC leading to a strong increase of transcription of target genes
CC (PubMed:10788465, PubMed:9192892). Interacts with NCOA7; the
CC interaction requires ligand-binding (By similarity). Interacts (via the
CC ligand-binding domain) with PRAME; interaction is direct and ligand
CC (retinoic acid)-dependent (By similarity). Interacts with PRKAR1A; the
CC interaction negatively regulates RARA transcriptional activity (By
CC similarity). Interacts with NCOR1; the interaction occurs in the
CC absence of ligand and represses transcriptional activity
CC (PubMed:17205979). Interacts with NCOR2 (By similarity). Interacts with
CC PRMT2 (By similarity). Interacts with LRIF1 (By similarity). Interacts
CC with ASXL1 and NCOA1 (By similarity). Interacts with ACTN4 (By
CC similarity). Interacts with CDK7; the interaction is enhanced by
CC interaction with GTF2H3 (PubMed:9230306). Interacts with GTF2H3; the
CC interaction requires prior phosphorylation on Ser-369 which then
CC enhances interaction with CDK7 (PubMed:19078967). In a complex with
CC 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 (By similarity). In the absence of hormonal ligand,
CC interacts with TACC1 (PubMed:20078863). {ECO:0000250|UniProtKB:P10276,
CC ECO:0000269|PubMed:10788465, ECO:0000269|PubMed:17205979,
CC ECO:0000269|PubMed:19078967, ECO:0000269|PubMed:20078863,
CC ECO:0000269|PubMed:9192892, ECO:0000269|PubMed:9230306}.
CC -!- INTERACTION:
CC P11416; Q8C050: Rps6ka5; NbExp=2; IntAct=EBI-346736, EBI-8391218;
CC P11416; Q16236: NFE2L2; Xeno; NbExp=2; IntAct=EBI-346736, EBI-2007911;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10660575,
CC ECO:0000269|PubMed:12079996}. Cytoplasm {ECO:0000269|PubMed:10660575,
CC ECO:0000269|PubMed:12079996}. Note=Nuclear localization depends on
CC ligand binding, phosphorylation and sumoylation (PubMed:10660575,
CC PubMed:12079996). Translocation to the nucleus is dependent on
CC activation of PKC and the downstream MAPK phosphorylation
CC (PubMed:10660575, PubMed:12079996). Increased nuclear localization upon
CC pulsatile shear stress (By similarity). {ECO:0000250|UniProtKB:P10276,
CC ECO:0000269|PubMed:10660575, ECO:0000269|PubMed:12079996}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha-1;
CC IsoId=P11416-1; Sequence=Displayed;
CC Name=Alpha-2;
CC IsoId=P11416-2; Sequence=VSP_003630;
CC -!- TISSUE SPECIFICITY: Expressed in Sertoli cells and germ cells.
CC {ECO:0000269|PubMed:17905941}.
CC -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:17905941}.
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:0000250|UniProtKB:P10276}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Phosphorylation
CC does not change during cell cycle. Phosphorylation on Ser-77 is crucial
CC for the N-terminal AF1 transcriptional activity. Under stress
CC conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-
CC 461 leading to RARA ubiquitination and degradation. Phosphorylation by
CC AKT1 inhibits the transactivation activity. On retinoic acid
CC stimulation, phosphorylation on Ser-369 by RPS6KA5 promotes interaction
CC with GTF2H3 and the CDK7-mediated phosphorylation of Ser-77.
CC {ECO:0000269|PubMed:12079996, ECO:0000269|PubMed:19078967,
CC ECO:0000269|PubMed:9230306}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: Acetylated; acetylation is increased upon pulsatile shear stress
CC and decreased upon oscillatory shear stress.
CC {ECO:0000250|UniProtKB:P10276}.
CC -!- DISRUPTION PHENOTYPE: Seminiferous tubules of 6 month-old animals
CC display varying degrees of testicular degeneration, with moderate to
CC severe levels of germ-cell degeneration. Epithelial cells in the
CC epididymis show general disorganization. Sperm count is reduced to
CC about 1.7% of wild-type and sperm mobility reduced by half. Rara and
CC Rarg, but not Rara and Rarb, double knockout mice exhibit growth
CC retardation after 3 weeks. Defects are found in the growth plates with
CC deficiency in cartilage. Growth retardation was noticable in limb
CC sketal elements such as femurs. Early lethality and male sterility due
CC to squamous metaplasia of the seminal vesicles and prostate are also
CC observed. {ECO:0000269|PubMed:15901285, ECO:0000269|PubMed:17905941,
CC ECO:0000269|PubMed:19389355}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; X56572; CAA39919.1; -; mRNA.
DR EMBL; X56565; CAA39917.1; -; mRNA.
DR EMBL; S56656; AAB25783.1; -; mRNA.
DR EMBL; X57528; CAA40749.1; -; mRNA.
DR EMBL; M60909; AAA40031.1; -; mRNA.
DR EMBL; BC010216; AAH10216.1; -; mRNA.
DR CCDS; CCDS36304.1; -. [P11416-1]
DR CCDS; CCDS48905.1; -. [P11416-2]
DR PIR; S05050; S05050.
DR RefSeq; NP_001169999.1; NM_001176528.1. [P11416-2]
DR RefSeq; NP_001170773.1; NM_001177302.1. [P11416-1]
DR RefSeq; NP_001170774.1; NM_001177303.1. [P11416-1]
DR RefSeq; NP_033050.2; NM_009024.2. [P11416-1]
DR RefSeq; XP_006532655.1; XM_006532592.3. [P11416-1]
DR RefSeq; XP_006532656.1; XM_006532593.2. [P11416-1]
DR RefSeq; XP_017169842.1; XM_017314353.1.
DR AlphaFoldDB; P11416; -.
DR SASBDB; P11416; -.
DR SMR; P11416; -.
DR BioGRID; 202586; 74.
DR ComplexPortal; CPX-584; RXRalpha-RARalpha retinoic acid receptor complex.
DR ComplexPortal; CPX-667; RARalpha-NCOA1 activated retinoic acid receptor complex.
DR ComplexPortal; CPX-668; RARalpha-NCOA2 activated retinoic acid receptor complex.
DR ComplexPortal; CPX-818; RXRalpha-RARalpha-NCOA2 retinoic acid receptor complex.
DR DIP; DIP-31480N; -.
DR IntAct; P11416; 15.
DR MINT; P11416; -.
DR STRING; 10090.ENSMUSP00000069744; -.
DR BindingDB; P11416; -.
DR ChEMBL; CHEMBL2792; -.
DR DrugCentral; P11416; -.
DR GuidetoPHARMACOLOGY; 590; -.
DR iPTMnet; P11416; -.
DR PhosphoSitePlus; P11416; -.
DR EPD; P11416; -.
DR MaxQB; P11416; -.
DR PaxDb; P11416; -.
DR PRIDE; P11416; -.
DR ProteomicsDB; 300233; -. [P11416-1]
DR ProteomicsDB; 300234; -. [P11416-2]
DR Antibodypedia; 16473; 821 antibodies from 47 providers.
DR DNASU; 19401; -.
DR Ensembl; ENSMUST00000068133; ENSMUSP00000069744; ENSMUSG00000037992. [P11416-1]
DR Ensembl; ENSMUST00000107473; ENSMUSP00000103097; ENSMUSG00000037992. [P11416-2]
DR Ensembl; ENSMUST00000107474; ENSMUSP00000103098; ENSMUSG00000037992. [P11416-1]
DR Ensembl; ENSMUST00000107475; ENSMUSP00000103099; ENSMUSG00000037992. [P11416-1]
DR Ensembl; ENSMUST00000164748; ENSMUSP00000129791; ENSMUSG00000037992. [P11416-1]
DR GeneID; 19401; -.
DR KEGG; mmu:19401; -.
DR UCSC; uc007lhx.1; mouse. [P11416-1]
DR UCSC; uc007lhz.2; mouse. [P11416-2]
DR CTD; 5914; -.
DR MGI; MGI:97856; Rara.
DR VEuPathDB; HostDB:ENSMUSG00000037992; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159997; -.
DR HOGENOM; CLU_007368_18_2_1; -.
DR InParanoid; P11416; -.
DR OMA; AGIQHQL; -.
DR OrthoDB; 1466354at2759; -.
DR PhylomeDB; P11416; -.
DR TreeFam; TF328382; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR Reactome; R-MMU-9616222; Transcriptional regulation of granulopoiesis.
DR BioGRID-ORCS; 19401; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Rara; mouse.
DR PRO; PR:P11416; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P11416; protein.
DR Bgee; ENSMUSG00000037992; Expressed in granulocyte and 202 other tissues.
DR ExpressionAtlas; P11416; baseline and differential.
DR Genevisible; P11416; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0051393; F:alpha-actinin binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISO:MGI.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:MGI.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0051018; F:protein kinase A binding; ISO:MGI.
DR GO; GO:0043422; F:protein kinase B binding; ISO:MGI.
DR GO; GO:0001972; F:retinoic acid binding; ISO:MGI.
DR GO; GO:0044323; F:retinoic acid-responsive element binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0060348; P:bone development; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:MGI.
DR GO; GO:0060591; P:chondroblast differentiation; IMP:MGI.
DR GO; GO:0031076; P:embryonic camera-type eye development; IGI:MGI.
DR GO; GO:0060324; P:face development; IGI:MGI.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IMP:UniProtKB.
DR GO; GO:0002068; P:glandular epithelial cell development; IGI:MGI.
DR GO; GO:0003417; P:growth plate cartilage development; IGI:MGI.
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; IGI:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; ISO:MGI.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IGI:MGI.
DR GO; GO:0061037; P:negative regulation of cartilage development; IMP:MGI.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:MGI.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; ISO:MGI.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:MGI.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0001843; P:neural tube closure; IGI:MGI.
DR GO; GO:0051099; P:positive regulation of binding; ISO:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; ISO:MGI.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISO:MGI.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; ISO:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030852; P:regulation of granulocyte differentiation; IMP:MGI.
DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; IMP:MGI.
DR GO; GO:0031641; P:regulation of myelination; ISO:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0032526; P:response to retinoic acid; IMP:MGI.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; ISO:MGI.
DR GO; GO:0060010; P:Sertoli cell fate commitment; IMP:UniProtKB.
DR GO; GO:0060534; P:trachea cartilage development; IMP:MGI.
DR GO; GO:0001657; P:ureteric bud development; IMP:MGI.
DR GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; IMP:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
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 Alternative splicing; Cytoplasm; Direct protein sequencing; DNA-binding;
KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..462
FT /note="Retinoic acid receptor alpha"
FT /id="PRO_0000053462"
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 420..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 408..416
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P10276"
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 MOD_RES 77
FT /note="Phosphoserine; by CDK7"
FT /evidence="ECO:0000269|PubMed:19078967,
FT ECO:0000269|PubMed:9230306"
FT MOD_RES 96
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:P10276"
FT MOD_RES 219
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10276"
FT MOD_RES 347
FT /note="N6,N6,N6-trimethyllysine"
FT /evidence="ECO:0000269|PubMed:17205979"
FT MOD_RES 369
FT /note="Phosphoserine; by PKA and RPS6KA5"
FT /evidence="ECO:0000269|PubMed:19078967"
FT CROSSLNK 166
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 171
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 399
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..60
FT /note="MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTSLQHQLPVSG
FT YSTPSPAT -> MYESVEVGGLTPAPNPFLVVDFYNQNRACLLQEKGLPAPGPYSTPLR
FT TPLWNGSNHS (in isoform Alpha-2)"
FT /evidence="ECO:0000303|PubMed:1846598"
FT /id="VSP_003630"
FT VARIANT 391
FT /note="G -> A (in embryonal carcinoma cell line RAC65)"
FT VARIANT 392..462
FT /note="Missing (in embryonal carcinoma cell line RAC65)"
FT MUTAGEN 74
FT /note="S->A: No effect on phosphorylation, no effect on
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:9230306"
FT MUTAGEN 77
FT /note="S->A: Decreases phosphorylation and no effect on
FT interaction with CDK7. Strongly reduces transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:19078967,
FT ECO:0000269|PubMed:9230306"
FT MUTAGEN 347
FT /note="K->A,Q: Greatly reduced interaction with RXRA and
FT NCOR1 and transcriptional activation."
FT /evidence="ECO:0000269|PubMed:17205979"
FT MUTAGEN 347
FT /note="K->F: Reduced methylation levels. Little effect on
FT interaction with RXRA or NCOR1. Small loss in
FT transcriptional activation."
FT /evidence="ECO:0000269|PubMed:17205979"
FT MUTAGEN 369
FT /note="S->A: Abolishes phosphorylation and prevents
FT phosphorylation of S-77."
FT /evidence="ECO:0000269|PubMed:19078967"
FT MUTAGEN 449
FT /note="S->A: No change in phosphorylation levels and no
FT effect on transcriptional activity."
FT /evidence="ECO:0000269|PubMed:9230306"
FT MUTAGEN 456
FT /note="S->A: No change in phosphorylation levels and no
FT effect on transcriptional activity."
FT /evidence="ECO:0000269|PubMed:9230306"
FT MUTAGEN 461
FT /note="S->A: No change in phosphorylation levels and no
FT effect on transcriptional activity."
FT /evidence="ECO:0000269|PubMed:9230306"
FT CONFLICT 163
FT /note="N -> K (in Ref. 5; AAA40031)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="T -> S (in Ref. 5; AAA40031)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="M -> L (in Ref. 5; AAA40031)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 462 AA; 50735 MW; 726F7799633A85AD CRC64;
MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTSLQHQLPV SGYSTPSPAT
IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM
VYTCHRDKNC IINKVTRNRC QYCRLQKCFD VGMSKESVRN DRNKKKKEAP KPECSESYTL
TPEVGELIEK VRKAHQETFP ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV
EFAKQLPGFT TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA
GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDKVDM LQEPLLEALK
VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGL
DTLSGQSGGG TRDGGGLAPP PGSCSPSLSP SSHRSSPATQ SP
