NR2F6_MOUSE
ID NR2F6_MOUSE Reviewed; 390 AA.
AC P43136; Q61504; Q922G8;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Nuclear receptor subfamily 2 group F member 6;
DE AltName: Full=COUP transcription factor 3;
DE Short=COUP-TF3;
DE AltName: Full=V-erbA-related protein 2;
DE Short=EAR-2;
GN Name=Nr2f6; Synonyms=Ear-2, Ear2, Erbal2;
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].
RX PubMed=7947324; DOI=10.1016/0925-4773(94)90098-1;
RA Jonk L.J.C., de Jonge M.E.J., Pals C.E.G.M., Wissink S., Vervaart J.M.A.,
RA Schoorlemmer J., Kruijer W.;
RT "Cloning and expression during development of three murine members of the
RT COUP family of nuclear orphan receptors.";
RL Mech. Dev. 47:81-97(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary;
RX PubMed=8194772; DOI=10.1016/0378-1119(94)90283-6;
RA Barnhart K.M., Mellon P.L.;
RT "The sequence of a murine cDNA encoding Ear-2, a nuclear orphan receptor.";
RL Gene 142:313-314(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [6]
RP SUBUNIT, AND INTERACTION WITH NR2F2.
RX PubMed=10318855; DOI=10.1074/jbc.274.20.14331;
RA Avram D., Ishmael J.E., Nevrivy D.J., Peterson V.J., Lee S.H., Dowell P.,
RA Leid M.;
RT "Heterodimeric interactions between chicken ovalbumin upstream promoter-
RT transcription factor family members ARP1 and ear2.";
RL J. Biol. Chem. 274:14331-14336(1999).
RN [7]
RP INTERACTION WITH ZFPM2.
RX PubMed=11382775; DOI=10.1074/jbc.m103577200;
RA Huggins G.S., Bacani C.J., Boltax J., Aikawa R., Leiden J.M.;
RT "Friend of GATA 2 physically interacts with chicken ovalbumin upstream
RT promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent
RT activation of the atrial natriuretic factor promoter.";
RL J. Biol. Chem. 276:28029-28036(2001).
RN [8]
RP FUNCTION, DNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=12690040; DOI=10.1161/01.res.0000071355.82009.43;
RA Liu X., Huang X., Sigmund C.D.;
RT "Identification of a nuclear orphan receptor (Ear2) as a negative regulator
RT of renin gene transcription.";
RL Circ. Res. 92:1033-1040(2003).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=15741322; DOI=10.1101/gad.317905;
RA Warnecke M., Oster H., Revelli J.P., Alvarez-Bolado G., Eichele G.;
RT "Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice
RT impairs the functionality of the forebrain clock and affects nociception.";
RL Genes Dev. 19:614-625(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18701084; DOI=10.1016/j.immuni.2008.06.008;
RA Hermann-Kleiter N., Gruber T., Lutz-Nicoladoni C., Thuille N., Fresser F.,
RA Labi V., Schiefermeier N., Warnecke M., Huber L., Villunger A., Eichele G.,
RA Kaminski S., Baier G.;
RT "The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T
RT helper 17-dependent autoimmunity.";
RL Immunity 29:205-216(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Transcription factor predominantly involved in
CC transcriptional repression. Binds to promoter/enhancer response
CC elements that contain the imperfect 5'-AGGTCA-3' direct or inverted
CC repeats with various spacings which are also recognized by other
CC nuclear hormone receptors. Involved in modulation of hormonal
CC responses. Represses transcriptional activity of the lutropin-
CC choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and
CC the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-
CC dependent and -independent transcriptional activity of the thyroid
CC hormone receptor gene in a cell type-specific manner. The corepressing
CC function towards thyroid hormone receptor beta/THRB involves at least
CC in part the inhibition of THRB binding to triiodothyronine response
CC elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA
CC binding and subsequently its transcriptional activity. Acts as
CC transcriptional repressor of IL-17 expression in Th-17 differentiated
CC CD4(+) T cells and may be involved in induction and/or maintenance of
CC peripheral immunological tolerance and autoimmunity. Involved in
CC development of forebrain circadian clock; is required early in the
CC development of the locus coeruleus (LC). {ECO:0000269|PubMed:12690040,
CC ECO:0000269|PubMed:15741322, ECO:0000269|PubMed:18701084}.
CC -!- SUBUNIT: Binds DNA as dimer; homodimer and heterodimer with NR2F2 and
CC probably NR2F1. Interacts with THRB (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P43136; O35626: Rasd1; NbExp=5; IntAct=EBI-4319956, EBI-4319979;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:12690040}.
CC -!- DEVELOPMENTAL STAGE: Initially expressed at 8.5 dpc in the developing
CC rhombencephalon. At 11.5 dpc expression in the CNS rapidly decreases
CC and in newborn and adult expression is not detectable in the brain with
CC the exceptions of Purkinje neurons and the choroid plexi.
CC {ECO:0000269|PubMed:15741322}.
CC -!- DISRUPTION PHENOTYPE: Reduction of neurons in the locus coerulus of the
CC developing cortex. Defects in circadian behavior. Hyperreactive
CC lymphocytes, late-onset immunopathology and hypersusceptibility to
CC Th17-dependent experimental autoimmune encephalomyelitis.
CC {ECO:0000269|PubMed:15741322, ECO:0000269|PubMed:18701084}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; X76654; CAA54097.1; -; mRNA.
DR EMBL; L25674; AAA37532.1; -; mRNA.
DR EMBL; AK131941; BAE20887.1; -; mRNA.
DR EMBL; AK171552; BAE42523.1; -; mRNA.
DR EMBL; CH466569; EDL28911.1; -; Genomic_DNA.
DR EMBL; BC008138; AAH08138.1; -; mRNA.
DR CCDS; CCDS22392.1; -.
DR PIR; I48734; S44285.
DR PIR; I49640; I49640.
DR RefSeq; NP_034280.2; NM_010150.2.
DR AlphaFoldDB; P43136; -.
DR SMR; P43136; -.
DR BioGRID; 199494; 7.
DR IntAct; P43136; 5.
DR STRING; 10090.ENSMUSP00000002466; -.
DR iPTMnet; P43136; -.
DR PhosphoSitePlus; P43136; -.
DR MaxQB; P43136; -.
DR PaxDb; P43136; -.
DR PeptideAtlas; P43136; -.
DR PRIDE; P43136; -.
DR ProteomicsDB; 293721; -.
DR Antibodypedia; 14278; 399 antibodies from 36 providers.
DR DNASU; 13864; -.
DR Ensembl; ENSMUST00000002466; ENSMUSP00000002466; ENSMUSG00000002393.
DR GeneID; 13864; -.
DR KEGG; mmu:13864; -.
DR UCSC; uc009mcx.1; mouse.
DR CTD; 2063; -.
DR MGI; MGI:1352453; Nr2f6.
DR VEuPathDB; HostDB:ENSMUSG00000002393; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000160748; -.
DR HOGENOM; CLU_007368_20_1_1; -.
DR InParanoid; P43136; -.
DR OMA; GWGNPNR; -.
DR OrthoDB; 666130at2759; -.
DR PhylomeDB; P43136; -.
DR TreeFam; TF352097; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 13864; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Nr2f6; mouse.
DR PRO; PR:P43136; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P43136; protein.
DR Bgee; ENSMUSG00000002393; Expressed in floor plate of midbrain and 261 other tissues.
DR ExpressionAtlas; P43136; baseline and differential.
DR Genevisible; P43136; MM.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
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:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0048666; P:neuron development; IMP:MGI.
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 DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..390
FT /note="Nuclear receptor subfamily 2 group F member 6"
FT /id="PRO_0000053614"
FT DOMAIN 157..380
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 54..129
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 57..77
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 93..117
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 314..390
FT /note="Important for dimerization"
FT /evidence="ECO:0000250"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10588"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10588"
FT CONFLICT 10
FT /note="D -> G (in Ref. 2; AAA37532)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="S -> T (in Ref. 1; CAA54097 and 2; AAA37532)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="P -> H (in Ref. 2; AAA37532)"
FT /evidence="ECO:0000305"
FT CONFLICT 164..165
FT /note="QL -> HV (in Ref. 2; AAA37532)"
FT /evidence="ECO:0000305"
FT CONFLICT 196..198
FT /note="LLF -> AV (in Ref. 2; AAA37532)"
FT /evidence="ECO:0000305"
FT CONFLICT 239..241
FT /note="LPL -> VAV (in Ref. 2; AAA37532)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="Q -> K (in Ref. 1; CAA54097)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 390 AA; 41968 MW; 4C30B25C6CAE5338 CRC64;
MAMVTGGWGD PGGDTNGVDK AGGSYPRATE DDSASPPGAT SDAEPGDEER PGLQVDCVVC
GDKSSGKHYG VFTCEGCKSF FKRSIRRNLS YTCRSNRDCQ IDQHHRNQCQ YCRLKKCFRV
GMRKEAVQRG RIPHALPGPA ACSPPGATGV EPFTGPPVSE LIAQLLRAEP YPAAGRFGGG
GAVLGIDNVC ELAARLLFST VEWARHAPFF PELPAADQVA LLRLSWSELF VLNAAQAALP
LHTAPLLAAA GLHAAPMAAE RAVAFMDQVR AFQEQVDKLG RLQVDAAEYG CLKAIALFTP
DACGLSDPAH VESLQEKAQV ALTEYVRAQY PSQPQRFGRL LLRLPALRAV PASLISQLFF
MRLVGKTPIE TLIRDMLLSG STFNWPYGSG
