NR2C1_MOUSE
ID NR2C1_MOUSE Reviewed; 590 AA.
AC Q505F1; P97763; Q0VGP8; Q3UIJ7; Q4U1Z4; Q60927; Q62152; Q8VIJ3;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Nuclear receptor subfamily 2 group C member 1;
DE AltName: Full=Orphan nuclear receptor TR2;
DE AltName: Full=Testicular receptor 2;
DE Short=mTR2;
GN Name=Nr2c1 {ECO:0000312|MGI:MGI:1352465};
GN Synonyms=Tr2, Tr2-11 {ECO:0000312|EMBL:AAC53253.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAC53253.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND VARIANTS MET-29; MET-145; 296-SER--LYS-304; ILE-361; ALA-377 AND
RP ALA-456.
RC STRAIN=CD-1 {ECO:0000312|EMBL:AAC53253.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:8595902};
RX PubMed=8595902; DOI=10.1006/geno.1995.0007;
RA Lee C.-H., Copeland N.G., Gilbert D.J., Jenkins N.A., Wei L.-N.;
RT "Genomic structure, promoter identification, and chromosomal mapping of a
RT mouse nuclear orphan receptor expressed in embryos and adult testes.";
RL Genomics 30:46-52(1995).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAC52787.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND VARIANTS MET-29; MET-145; 296-SER--LYS-304;
RP ILE-361; ALA-377 AND ALA-456.
RC STRAIN=CD-1 {ECO:0000312|EMBL:AAC52787.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:8858600};
RX PubMed=8858600;
RX DOI=10.1002/(sici)1098-2795(199607)44:3<305::aid-mrd4>3.0.co;2-q;
RA Lee C.-H., Chang L., Wei L.N.;
RT "Molecular cloning and characterization of a mouse nuclear orphan receptor
RT expressed in embryos and testes.";
RL Mol. Reprod. Dev. 44:305-314(1996).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=9071982; DOI=10.1677/joe.0.1520245;
RA Lee C.-H., Chang L., Wei L.-N.;
RT "Distinct expression patterns and biological activities of two isoforms of
RT the mouse orphan receptor TR2.";
RL J. Endocrinol. 152:245-255(1997).
RN [4] {ECO:0000305, ECO:0000312|EMBL:CAA72244.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C3H X 102 {ECO:0000269|PubMed:9504722};
RX PubMed=9504722;
RA Immervoll T., Adamski J., Graw J.;
RT "Polymorphism in the murine Tr2-11 gene encoding an orphan receptor, and
RT its exclusion as a candidate gene for the cataract mutation Cat3.";
RL Biol. Chem. 379:83-85(1998).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAC29502.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAC29502.1};
RC TISSUE=Testis {ECO:0000312|EMBL:AAC29502.1};
RX PubMed=9694834; DOI=10.1074/jbc.273.33.20877;
RA Young W.-J., Lee Y.-F., Smith S.M., Chang C.;
RT "A bidirectional regulation between the TR2/TR4 orphan receptors (TR2/TR4)
RT and the ciliary neurotrophic factor (CNTF) signaling pathway.";
RL J. Biol. Chem. 273:20877-20885(1998).
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAL31315.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RA Ideta R., Yeh S., Lee Y.-F., Adachi K., Takeda H., Su C., Chang C.;
RT "Cloning, antibody production and immunohistochemical localization of an
RT androgen repressed of mouse and rat TR2 orphan receptors: a member of
RT steroid receptor superfamily.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000305, ECO:0000312|EMBL:BAE28842.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE28842.1};
RC TISSUE=Embryonic kidney {ECO:0000269|PubMed:16141072}, and
RC Liver tumor {ECO:0000312|EMBL:BAE28842.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [9] {ECO:0000305, ECO:0000312|EMBL:AAH94580.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH94580.1};
RC TISSUE=Eye {ECO:0000312|EMBL:AAH94580.1};
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 [10]
RP DNA-BINDING, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8530418; DOI=10.1074/jbc.270.50.29636;
RA Lin T.M., Young W.J., Chang C.;
RT "Multiple functions of the TR2-11 orphan receptor in modulating activation
RT of two key cis-acting elements involved in the retinoic acid signal
RT transduction system.";
RL J. Biol. Chem. 270:30121-30128(1995).
RN [11] {ECO:0000305}
RP DNA-BINDING, AND HOMODIMERIZATION.
RX PubMed=9369481; DOI=10.1021/bi971598z;
RA Chinpaisal C., Chang L., Hu X., Lee C.-H., Wen W.-N., Wei L.-N.;
RT "The orphan nuclear receptor TR2 suppresses a DR4 hormone response element
RT of the mouse CRABP-I gene promoter.";
RL Biochemistry 36:14088-14095(1997).
RN [12] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NRIP1.
RX PubMed=9774688; DOI=10.1128/mcb.18.11.6745;
RA Lee C.-H., Chinpaisal C., Wei L.-N.;
RT "Cloning and characterization of mouse RIP140, a corepressor for nuclear
RT orphan receptor TR2.";
RL Mol. Cell. Biol. 18:6745-6755(1998).
RN [13] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH HDAC3 AND HDAC4.
RX PubMed=11463856; DOI=10.1210/mend.15.8.0682;
RA Franco P.J., Farooqui M., Seto E., Wei L.-N.;
RT "The orphan nuclear receptor TR2 interacts directly with both class I and
RT class II histone deacetylases.";
RL Mol. Endocrinol. 15:1318-1328(2001).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY IN DRED COMPLEX, FUNCTION, SUBCELLULAR
RP LOCATION, HETERODIMERIZATION, AND DEVELOPMENTAL STAGE.
RX PubMed=12093744; DOI=10.1093/emboj/cdf340;
RA Tanabe O., Katsuoka F., Campbell A.D., Song W., Yamamoto M., Tanimoto K.,
RA Engel J.D.;
RT "An embryonic/fetal beta-type globin gene repressor contains a nuclear
RT receptor TR2/TR4 heterodimer.";
RL EMBO J. 21:3434-3442(2002).
RN [15]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=12052874; DOI=10.1128/mcb.22.13.4661-4666.2002;
RA Shyr C.R., Collins L.L., Mu X.M., Platt K.A., Chang C.;
RT "Spermatogenesis and testis development are normal in mice lacking
RT testicular orphan nuclear receptor 2.";
RL Mol. Cell. Biol. 22:4661-4666(2002).
RN [16]
RP PHOSPHORYLATION AT SER-461 AND SER-568, FUNCTION, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=16130175; DOI=10.1002/pmic.200402062;
RA Khan S.A., Park S.W., Huq M., Wei L.N.;
RT "Protein kinase C-mediated phosphorylation of orphan nuclear receptor TR2:
RT effects on receptor stability and activity.";
RL Proteomics 5:3885-3894(2005).
RN [17]
RP PHOSPHORYLATION AT SER-185, DNA-BINDING, FUNCTION, INTERACTION WITH KAT2B,
RP AND MUTAGENESIS OF SER-170 AND SER-185.
RX PubMed=16317770; DOI=10.1002/pmic.200500068;
RA Khan S.A., Park S.W., Huq M.D., Wei L.N.;
RT "Ligand-independent orphan receptor TR2 activation by phosphorylation at
RT the DNA-binding domain.";
RL Proteomics 6:123-130(2006).
RN [18]
RP FUNCTION, AND HETERODIMERIZATION.
RX PubMed=17431400; DOI=10.1038/sj.emboj.7601676;
RA Tanabe O., McPhee D., Kobayashi S., Shen Y., Brandt W., Jiang X.,
RA Campbell A.D., Chen Y.T., Chang C., Yamamoto M., Tanimoto K., Engel J.D.;
RT "Embryonic and fetal beta-globin gene repression by the orphan nuclear
RT receptors, TR2 and TR4.";
RL EMBO J. 26:2295-2306(2007).
RN [19]
RP HETERODIMERIZATION, AND FUNCTION.
RX PubMed=17974920; DOI=10.1101/gad.1593307;
RA Tanabe O., Shen Y., Liu Q., Campbell A.D., Kuroha T., Yamamoto M.,
RA Engel J.D.;
RT "The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription.";
RL Genes Dev. 21:2832-2844(2007).
RN [20]
RP SUMOYLATION AT LYS-238, SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH
RP KAT2B; NRIP1; PIAS1 AND UBE2I, AND MUTAGENESIS OF LYS-167; LYS-238; GLU-240
RP AND LYS-575.
RX PubMed=17187077; DOI=10.1038/nsmb1185;
RA Park S.W., Hu X., Gupta P., Lin Y.P., Ha S.G., Wei L.N.;
RT "SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4
RT expression in stem cells.";
RL Nat. Struct. Mol. Biol. 14:68-75(2007).
RN [21]
RP FUNCTION.
RX PubMed=17389641; DOI=10.1093/nar/gkl1147;
RA Gupta P., Park S.W., Farooqui M., Wei L.N.;
RT "Orphan nuclear receptor TR2, a mediator of preadipocyte proliferation, is
RT differentially regulated by RA through exchange of coactivator PCAF with
RT corepressor RIP140 on a platform molecule GRIP1.";
RL Nucleic Acids Res. 35:2269-2282(2007).
RN [22]
RP PHOSPHORYLATION AT SER-203; THR-208 AND THR-210, SUMOYLATION, INTERACTION
RP WITH KAT2B, MUTAGENESIS OF SER-170; SER-185; SER-203; THR-208; THR-210;
RP LYS-238; SER-461 AND SER-568, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18682553; DOI=10.1073/pnas.0710561105;
RA Gupta P., Ho P.C., Huq M.M., Ha S.G., Park S.W., Khan A.A., Tsai N.P.,
RA Wei L.N.;
RT "Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and
RT SUMOylation of nuclear receptor TR2 to suppress Oct4 expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11424-11429(2008).
RN [23]
RP DISRUPTION PHENOTYPE, INDUCTION, AND FUNCTION.
RX PubMed=19131575; DOI=10.1210/en.2008-1165;
RA Shyr C.R., Kang H.Y., Tsai M.Y., Liu N.C., Ku P.Y., Huang K.E., Chang C.;
RT "Roles of testicular orphan nuclear receptors 2 and 4 in early embryonic
RT development and embryonic stem cells.";
RL Endocrinology 150:2454-2462(2009).
RN [24]
RP SUMOYLATION, INTERACTION WITH HDAC3, AND SUBCELLULAR LOCATION.
RX PubMed=19204783; DOI=10.1371/journal.pone.0004363;
RA Gupta P., Ho P.C., Ha S.G., Lin Y.W., Wei L.N.;
RT "HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a
RT novel deacetylase activity-independent function of HDAC3.";
RL PLoS ONE 4:E4363-E4363(2009).
CC -!- FUNCTION: Orphan nuclear receptor. Binds the IR7 element in the
CC promoter of its own gene in an autoregulatory negative feedback
CC mechanism. Primarily repressor of a broad range of genes including ESR1
CC and RARB. Together with NR2C2, forms the core of the DRED (direct
CC repeat erythroid-definitive) complex that represses embryonic and fetal
CC globin transcription. Binds to hormone response elements (HREs)
CC consisting of two 5'-AGGTCA-3' half site direct repeat consensus
CC sequences (By similarity). Also activator of OCT4 gene expression.
CC Plays a fundamental role in early embryogenesis and regulates embryonic
CC stem cell proliferation and differentiation. Mediator of retinoic acid-
CC regulated preadipocyte proliferation. {ECO:0000250,
CC ECO:0000269|PubMed:11463856, ECO:0000269|PubMed:12093744,
CC ECO:0000269|PubMed:16130175, ECO:0000269|PubMed:16317770,
CC ECO:0000269|PubMed:17187077, ECO:0000269|PubMed:17389641,
CC ECO:0000269|PubMed:17431400, ECO:0000269|PubMed:17974920,
CC ECO:0000269|PubMed:19131575, ECO:0000269|PubMed:8530418,
CC ECO:0000269|PubMed:8858600, ECO:0000269|PubMed:9071982,
CC ECO:0000269|PubMed:9774688}.
CC -!- SUBUNIT: Homodimer. Heterodimer; with NR2C2 which is required for
CC chromatin remodeling and for binding to promoter regions such as globin
CC DR1 repeats. Interacts with ESR1; the interaction prevents
CC homodimerization of ESR1 and suppresses its transcriptional activity
CC and cell growth (By similarity). Interacts with NRIP1 (via its LXXLL
CC motifs); the interaction provides corepressor activity. Interacts with
CC HDAC3 (via the DNA-binding domain); the interaction recruits
CC phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with
CC HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the
CC interaction is required for sumoylation of NR2C1. Interacts with UBE2I;
CC the interaction is required for sumoylation of NR2C1. Interacts with
CC KAT2B; the interaction acts as a corepressor of gene expression.
CC {ECO:0000250, ECO:0000269|PubMed:11463856, ECO:0000269|PubMed:16317770,
CC ECO:0000269|PubMed:17187077, ECO:0000269|PubMed:18682553,
CC ECO:0000269|PubMed:19204783, ECO:0000269|PubMed:9774688}.
CC -!- INTERACTION:
CC Q505F1; Q9JHD1: Kat2b; NbExp=3; IntAct=EBI-15617004, EBI-2325611;
CC Q505F1; Q8CBD1: Nrip1; NbExp=3; IntAct=EBI-15617004, EBI-1771626;
CC Q505F1; O88907: Pias1; NbExp=4; IntAct=EBI-15617004, EBI-3508327;
CC Q505F1; Q60953: Pml; NbExp=2; IntAct=EBI-15617004, EBI-3895605;
CC Q505F1; Q8BSJ6: Pml; NbExp=3; IntAct=EBI-15617004, EBI-15719975;
CC Q505F1; P63166: Sumo1; NbExp=5; IntAct=EBI-15617004, EBI-80152;
CC Q505F1; P63280: Ube2i; NbExp=3; IntAct=EBI-15617004, EBI-80180;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, PML body. Note=Recruited by
CC HDAC3, after all-trans retinoic acid stimulated MAPK1-mediated Thr-210
CC phosphorylation, to PML bodies for subsequent sumoylation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:8858600, ECO:0000269|PubMed:9504722,
CC ECO:0000269|PubMed:9694834};
CC IsoId=Q505F1-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:9071982}; Synonyms=TR2-11-t
CC {ECO:0000303|PubMed:9071982}, TR2-11-truncated
CC {ECO:0000303|PubMed:9071982};
CC IsoId=Q505F1-2; Sequence=VSP_051921, VSP_051922;
CC -!- TISSUE SPECIFICITY: Isoform 1 is highly expressed in the adlumenal
CC compartment of the seminiferous tubule of adult testes (at protein
CC level) and in the eyes of newborn animals. Weakly expressed in other
CC adult organs including the seminal vesicle, prostate, ovary, adrenal
CC gland, heart, thymus, placenta and brain. Expressed during embryonic
CC stages in developing eyes, brain and cartilage primordia (at protein
CC level). Also expressed in the developing spinal motor neurons and in
CC the sympathetic-, parasympathetic- and sensory ganglia of the embryonic
CC PNS. Expressed in the developing neural epithelia of the inner ear,
CC nasal cavity, tongue and retina. At day 16.5, expressed in various
CC tissues including kidney and intestine. In contrast, isoform 2 is
CC widely expressed at a low level throughout the adult testis.
CC {ECO:0000269|PubMed:12052874, ECO:0000269|PubMed:8530418,
CC ECO:0000269|PubMed:8595902, ECO:0000269|PubMed:8858600,
CC ECO:0000269|PubMed:9071982, ECO:0000269|PubMed:9504722,
CC ECO:0000269|PubMed:9694834}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 is highly expressed in early to
CC midgestation embryos, with expression leveling off at 15 dpc. Expressed
CC in yolk sac erythrocytes at 9.5 dpc. After birth, expression in the
CC testes remains at a basal level until puberty, begins to increase at
CC postnatal day 16 (P16) and peaks at P20 to P24. Expression is
CC maintained at a high level throughout adulthood. Isoform 2 peaks
CC transiently at P24. {ECO:0000269|PubMed:12093744,
CC ECO:0000269|PubMed:8595902, ECO:0000269|PubMed:8858600,
CC ECO:0000269|PubMed:9071982}.
CC -!- INDUCTION: By ciliary neurotrophic factor (CNTF). Repressed by vitamin
CC A. Induced by retinoic acid. {ECO:0000269|PubMed:19131575,
CC ECO:0000269|PubMed:9694834}.
CC -!- PTM: Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to
CC dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction
CC with NRIP1 but inhibits interaction with KAT2B. In proliferating cells,
CC stimulation by all-trans retinoic acid, activation of MAPK1-mediated
CC phosphorylation and recruitment to PML bodies with subsequent
CC sumoylation, suppresses OCT4 expression.
CC -!- PTM: Phosphorylated on several serine and threonine residues.
CC Phosphorylation on Thr-210, stimulated by all-trans retinoic acid
CC (atRA) mediates PML location and sumoylation in proliferating cells
CC which then modulates its association with effector molecules, KAT2B and
CC NRIP1. Phosphorylation on Ser-568 by PKC is important for protein
CC stability and function as activator of RARB.
CC {ECO:0000269|PubMed:16130175, ECO:0000269|PubMed:18682553}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice exhibit normal
CC spermatogenesis and testis development, as well as normal central
CC nervous system development. NR2C1 and NR2C2 double null mutants result
CC in early embryonic lethality and increased apoptosis. Embryos die
CC around 7.5 dpc. {ECO:0000269|PubMed:12052874,
CC ECO:0000269|PubMed:19131575}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention.
CC {ECO:0000303|PubMed:9071982}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000255}.
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DR EMBL; U28280; AAC53253.1; -; Genomic_DNA.
DR EMBL; U28269; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28270; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28271; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28272; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28273; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28274; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28275; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28276; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28277; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28278; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28279; AAC53253.1; JOINED; Genomic_DNA.
DR EMBL; U28265; AAC52787.1; -; mRNA.
DR EMBL; Y11436; CAA72244.1; -; mRNA.
DR EMBL; U30482; AAC29502.1; -; mRNA.
DR EMBL; L26957; AAL31315.1; -; mRNA.
DR EMBL; AK146891; BAE27509.1; -; mRNA.
DR EMBL; AK149374; BAE28842.1; -; mRNA.
DR EMBL; AC127596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090662; AAH90662.1; -; mRNA.
DR EMBL; BC094580; AAH94580.1; -; mRNA.
DR CCDS; CCDS24131.1; -. [Q505F1-1]
DR RefSeq; NP_035759.3; NM_011629.3. [Q505F1-1]
DR RefSeq; XP_006513655.1; XM_006513592.2. [Q505F1-1]
DR AlphaFoldDB; Q505F1; -.
DR BioGRID; 204299; 2.
DR DIP; DIP-29275N; -.
DR IntAct; Q505F1; 7.
DR STRING; 10090.ENSMUSP00000100927; -.
DR iPTMnet; Q505F1; -.
DR PhosphoSitePlus; Q505F1; -.
DR EPD; Q505F1; -.
DR jPOST; Q505F1; -.
DR MaxQB; Q505F1; -.
DR PaxDb; Q505F1; -.
DR PeptideAtlas; Q505F1; -.
DR PRIDE; Q505F1; -.
DR ProteomicsDB; 293719; -. [Q505F1-1]
DR ProteomicsDB; 293720; -. [Q505F1-2]
DR Antibodypedia; 4166; 446 antibodies from 37 providers.
DR DNASU; 22025; -.
DR Ensembl; ENSMUST00000092213; ENSMUSP00000089858; ENSMUSG00000005897. [Q505F1-1]
DR Ensembl; ENSMUST00000099343; ENSMUSP00000096945; ENSMUSG00000005897. [Q505F1-1]
DR Ensembl; ENSMUST00000105290; ENSMUSP00000100927; ENSMUSG00000005897. [Q505F1-1]
DR GeneID; 22025; -.
DR KEGG; mmu:22025; -.
DR UCSC; uc007gvo.2; mouse. [Q505F1-1]
DR CTD; 7181; -.
DR MGI; MGI:1352465; Nr2c1.
DR VEuPathDB; HostDB:ENSMUSG00000005897; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000158165; -.
DR HOGENOM; CLU_007368_16_2_1; -.
DR InParanoid; Q505F1; -.
DR OMA; RKPIEMS; -.
DR OrthoDB; 278171at2759; -.
DR PhylomeDB; Q505F1; -.
DR TreeFam; TF316650; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 22025; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Nr2c1; mouse.
DR PRO; PR:Q505F1; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q505F1; protein.
DR Bgee; ENSMUSG00000005897; Expressed in spermatid and 228 other tissues.
DR Genevisible; Q505F1; MM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
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 Activator; Alternative splicing; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..590
FT /note="Nuclear receptor subfamily 2 group C member 1"
FT /id="PRO_0000053587"
FT DOMAIN 333..577
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 98..173
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 101..121
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 137..156
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..166
FT /note="Required for interaction with KAT2B"
FT REGION 571..590
FT /note="Required for interaction with NRIP1"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16317770"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18682553"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18682553"
FT MOD_RES 210
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:18682553"
FT MOD_RES 461
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:16130175"
FT MOD_RES 568
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:16130175"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000269|PubMed:17187077"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT CROSSLNK 575
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT VAR_SEQ 220..256
FT /note="SAGLLDSGMFVNIHPSGIKTEPAMLMAPDKAESCQGD -> CPAAISASFAS
FT LPRSTETKTCASFVAGQLDCWIQECL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9071982"
FT /id="VSP_051921"
FT VAR_SEQ 257..590
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9071982"
FT /id="VSP_051922"
FT VARIANT 29
FT /note="I -> M (in strain: CD-1)"
FT /evidence="ECO:0000269|PubMed:8595902,
FT ECO:0000269|PubMed:8858600"
FT VARIANT 145
FT /note="I -> M (in strain: CD-1)"
FT /evidence="ECO:0000269|PubMed:8595902,
FT ECO:0000269|PubMed:8858600"
FT VARIANT 296..304
FT /note="FGAFHHDIQ -> SVLFIMIFK (in strain: CD-1)"
FT /evidence="ECO:0000269|PubMed:8595902,
FT ECO:0000269|PubMed:8858600"
FT VARIANT 361
FT /note="V -> I (in strain: CD-1)"
FT /evidence="ECO:0000269|PubMed:8595902,
FT ECO:0000269|PubMed:8858600"
FT VARIANT 377
FT /note="V -> A (in strain: CD-1)"
FT /evidence="ECO:0000269|PubMed:8595902,
FT ECO:0000269|PubMed:8858600"
FT VARIANT 456
FT /note="P -> A (in strain: CD-1)"
FT /evidence="ECO:0000269|PubMed:8595902,
FT ECO:0000269|PubMed:8858600"
FT MUTAGEN 167
FT /note="K->A: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:17187077"
FT MUTAGEN 170
FT /note="S->A: No effect on sumoylation nor on DNA-binding
FT and little effect on binding KAT2B. Greatly reduced DNA-
FT binding, binding to KAT2B and activation of the RARB
FT promoter; when associated with A-185."
FT /evidence="ECO:0000269|PubMed:16317770,
FT ECO:0000269|PubMed:18682553"
FT MUTAGEN 185
FT /note="S->A: No effect on sumoylation and little effect on
FT binding KAT2B. Some reduced DNA-binding. Greatly reduced
FT DNA-binding, binding to KAT2B and activation of the RARB
FT promoter; when associated with A-170."
FT /evidence="ECO:0000269|PubMed:16317770,
FT ECO:0000269|PubMed:18682553"
FT MUTAGEN 203
FT /note="S->A: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 208
FT /note="T->A: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 210
FT /note="T->A: Abolishes sumoylation. No repression of OCT4
FT gene expression with or without retinoic acid and enhanced
FT interaction with KAT2B and HDAC3. Abolishes interaction
FT with HDAC3 and PML association; when associated with R-
FT 238."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 210
FT /note="T->E: Sumoylated. Repressed OCT4 gene expression.
FT Enhanced interaction with KAT2B; when associated with R-
FT 238."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 238
FT /note="K->A: Abolishes sumoylation. Strongly associated
FT with PML nuclear bodies. No effect on activation of OCT4
FT but activation not suppressed by additional SUMO1.
FT Increased binding to KAT2B and reduced binding to NRIP1.
FT Abolishes PML association; when associated with A-210."
FT /evidence="ECO:0000269|PubMed:17187077,
FT ECO:0000269|PubMed:18682553"
FT MUTAGEN 238
FT /note="K->R: Abolishes sumoylation. No effect on activation
FT of OCT4 but activation not suppressed by additional SUMO1.
FT Enhanced interaction with KAT2B; when associated with A-210
FT or E-210."
FT /evidence="ECO:0000269|PubMed:17187077,
FT ECO:0000269|PubMed:18682553"
FT MUTAGEN 240
FT /note="E->A: Abolishes sumoylation."
FT /evidence="ECO:0000269|PubMed:17187077"
FT MUTAGEN 461
FT /note="S->A: Little effect on PKC-stimulated protein
FT stability nor on activation of RARB reporter."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 461
FT /note="S->A: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 568
FT /note="S->A: Greatly reduced PKC-stimulated protein
FT stability and activation of RARB reporter."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 568
FT /note="S->A: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:18682553"
FT MUTAGEN 575
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:17187077"
FT CONFLICT 88
FT /note="K -> N (in Ref. 4; CAA72244, 5; AAC29502 and 6;
FT AAL31315)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="D -> N (in Ref. 5; AAC29502 and 6; AAL31315)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="A -> T (in Ref. 5; AAC29502 and 6; AAL31315)"
FT /evidence="ECO:0000305"
FT CONFLICT 326..327
FT /note="SA -> TS (in Ref. 1; AAC52787/AAC53253, 4; CAA72244
FT and 6; AAL31315)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="P -> S (in Ref. 5; AAC29502 and 6; AAL31315)"
FT /evidence="ECO:0000305"
FT CONFLICT 529
FT /note="D -> N (in Ref. 7; BAE27509)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 590 AA; 65476 MW; E639AF3E5312918D CRC64;
MATIEEIAHQ IIDQQMGEIV TEQQTGQKIQ IVTALDHSTQ GKQFILANHE GSTPGKVFLT
TPDAAGVNQL FFTSPDLSAP HLQLLTEKSP DQGPNKVFDL CVVCGDKASG RHYGAITCEG
CKGFFKRSIR KNLVYSCRGS KDCVINKHHR NRCQYCRLQR CIAFGMKQDS VQCERKPIEV
SREKSSNCAA STEKIYIRKD LRSPLAATPT FVTDSETARS AGLLDSGMFV NIHPSGIKTE
PAMLMAPDKA ESCQGDLSTL ASVVTSLANL GKAKDLSHCG GDMPVVQSLR NGDTSFGAFH
HDIQTNGDVS RAFDTLAKAL TPGESSACQS PEEGMEGSPH LIAGEPSFVE KEGPLLSESH
VAFRLTMPSP MPEYLNVHYI GESASRLLFL SMHWALSIPS FQALGQENSI SLVKAYWNEL
FTLGLAQCWQ VMNVATILAT FVNCLHSSLQ QDKMSPERRK SLMEHIFKLQ EFCNSMVKLC
IDGHEYAYLK AIVLFSPDHP GLENMELIER FQEKAYVEFQ DYITRTYPDD TYRLSRLLLR
LPALRLMNAT ITEELFFKGL IGNVRIDSVI PHILKMEPAD YNSQIIGHSL
