NR1D1_MOUSE
ID NR1D1_MOUSE Reviewed; 615 AA.
AC Q3UV55; Q3UJJ1; Q62171; Q6EEZ6; Q922A5; Q9ESY4;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Nuclear receptor subfamily 1 group D member 1;
DE AltName: Full=Rev-erbA-alpha;
DE AltName: Full=V-erbA-related protein 1;
DE Short=EAR-1;
GN Name=Nr1d1; Synonyms=Ear1;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, DBA/2J, and NOD; TISSUE=Bone, and Cerebellum;
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 [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-186.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RA Sadek M.M., Chen Y., Elbrecht A.;
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-55.
RC STRAIN=BALB/cJ; TISSUE=Skeletal muscle;
RA Chomez P., Vennstrom B.;
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
RC STRAIN=C57BL/6N;
RX PubMed=15591021; DOI=10.1677/jme.1.01554;
RA Triqueneaux G., Thenot S., Kakizawa T., Antoch M.P., Safi R.,
RA Takahashi J.S., Delaunay F., Laudet V.;
RT "The orphan receptor Rev-erbalpha gene is a target of the circadian clock
RT pacemaker.";
RL J. Mol. Endocrinol. 33:585-608(2004).
RN [7]
RP INTERACTION WITH C1D.
RX PubMed=9405624; DOI=10.1073/pnas.94.26.14400;
RA Zamir I., Dawson J., Lavinsky R.M., Glass C.K., Rosenfeld M.G., Lazar M.A.;
RT "Cloning and characterization of a corepressor and potential component of
RT the nuclear hormone receptor repression complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14400-14405(1997).
RN [8]
RP INDUCTION.
RX PubMed=14645221; DOI=10.1074/jbc.m311973200;
RA Curtis A.M., Seo S.B., Westgate E.J., Rudic R.D., Smyth E.M.,
RA Chakravarti D., FitzGerald G.A., McNamara P.;
RT "Histone acetyltransferase-dependent chromatin remodeling and the vascular
RT clock.";
RL J. Biol. Chem. 279:7091-7097(2004).
RN [9]
RP FUNCTION.
RX PubMed=18565334; DOI=10.1053/j.gastro.2008.05.035;
RA Duez H., van der Veen J.N., Duhem C., Pourcet B., Touvier T., Fontaine C.,
RA Derudas B., Bauge E., Havinga R., Bloks V.W., Wolters H.,
RA van der Sluijs F.H., Vennstrom B., Kuipers F., Staels B.;
RT "Regulation of bile acid synthesis by the nuclear receptor Rev-erbalpha.";
RL Gastroenterology 135:689-698(2008).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND PROTEASOMAL DEGRADATION.
RX PubMed=18227153; DOI=10.1128/mcb.01608-07;
RA Wang J., Lazar M.A.;
RT "Bifunctional role of Rev-erbalpha in adipocyte differentiation.";
RL Mol. Cell. Biol. 28:2213-2220(2008).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18454201; DOI=10.1371/journal.pgen.1000023;
RA Liu A.C., Tran H.G., Zhang E.E., Priest A.A., Welsh D.K., Kay S.A.;
RT "Redundant function of REV-ERBalpha and beta and non-essential role for
RT Bmal1 cycling in transcriptional regulation of intracellular circadian
RT rhythms.";
RL PLoS Genet. 4:E1000023-E1000023(2008).
RN [12]
RP FUNCTION.
RX PubMed=19710360; DOI=10.1101/gad.1825809;
RA Wu N., Yin L., Hanniman E.A., Joshi S., Lazar M.A.;
RT "Negative feedback maintenance of heme homeostasis by its receptor, Rev-
RT erbalpha.";
RL Genes Dev. 23:2201-2209(2009).
RN [13]
RP FUNCTION.
RX PubMed=19721697; DOI=10.1371/journal.pbio.1000181;
RA Le Martelot G., Claudel T., Gatfield D., Schaad O., Kornmann B.,
RA Lo Sasso G., Moschetta A., Schibler U.;
RT "REV-ERBalpha participates in circadian SREBP signaling and bile acid
RT homeostasis.";
RL PLoS Biol. 7:E1000181-E1000181(2009).
RN [14]
RP FUNCTION IN CIRCADIAN RHYTHMS, INTERACTION WITH PER2, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF LYS-456.
RX PubMed=20159955; DOI=10.1101/gad.564110;
RA Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.;
RT "The mammalian clock component PERIOD2 coordinates circadian output by
RT interaction with nuclear receptors.";
RL Genes Dev. 24:345-357(2010).
RN [15]
RP UBIQUITINATION AND PROTEASOMAL DEGRADATION.
RX PubMed=20534529; DOI=10.1073/pnas.1000438107;
RA Yin L., Joshi S., Wu N., Tong X., Lazar M.A.;
RT "E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the
RT circadian heme receptor Rev-erb alpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11614-11619(2010).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH OPHN1, PROTEASOMAL
RP DEGRADATION, AND TISSUE SPECIFICITY.
RX PubMed=21874017; DOI=10.1038/nn.2911;
RA Valnegri P., Khelfaoui M., Dorseuil O., Bassani S., Lagneaux C.,
RA Gianfelice A., Benfante R., Chelly J., Billuart P., Sala C., Passafaro M.;
RT "A circadian clock in hippocampus is regulated by interaction between
RT oligophrenin-1 and Rev-erbalpha.";
RL Nat. Neurosci. 14:1293-1301(2011).
RN [17]
RP INTERACTION WITH PER2.
RX PubMed=22170608; DOI=10.1038/nature10700;
RA Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W.,
RA Downes M., Evans R.M.;
RT "Cryptochromes mediate rhythmic repression of the glucocorticoid
RT receptor.";
RL Nature 480:552-556(2011).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21408158; DOI=10.1371/journal.pone.0017494;
RA Mollema N.J., Yuan Y., Jelcick A.S., Sachs A.J., von Alpen D.,
RA Schorderet D., Escher P., Haider N.B.;
RT "Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to
RT regulate transcriptional networks in the retina.";
RL PLoS ONE 6:E17494-E17494(2011).
RN [19]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22166979; DOI=10.1210/en.2011-1595;
RA Vieira E., Marroqui L., Batista T.M., Caballero-Garrido E., Carneiro E.M.,
RA Boschero A.C., Nadal A., Quesada I.;
RT "The clock gene Rev-erbalpha regulates pancreatic beta-cell function:
RT modulation by leptin and high-fat diet.";
RL Endocrinology 153:592-601(2012).
RN [20]
RP FUNCTION.
RX PubMed=22474260; DOI=10.1101/gad.186858.112;
RA Bugge A., Feng D., Everett L.J., Briggs E.R., Mullican S.E., Wang F.,
RA Jager J., Lazar M.A.;
RT "Rev-erbalpha and Rev-erbbeta coordinately protect the circadian clock and
RT normal metabolic function.";
RL Genes Dev. 26:657-667(2012).
RN [21]
RP FUNCTION, INTERACTION WITH SP1, AND INDUCTION.
RX PubMed=22549838; DOI=10.1038/ncomms1812;
RA Negoro H., Kanematsu A., Doi M., Suadicani S.O., Matsuo M., Imamura M.,
RA Okinami T., Nishikawa N., Oura T., Matsui S., Seo K., Tainaka M., Urabe S.,
RA Kiyokage E., Todo T., Okamura H., Tabata Y., Ogawa O.;
RT "Involvement of urinary bladder Connexin43 and the circadian clock in
RT coordination of diurnal micturition rhythm.";
RL Nat. Commun. 3:809-809(2012).
RN [22]
RP FUNCTION.
RX PubMed=22184247; DOI=10.1073/pnas.1106750109;
RA Gibbs J.E., Blaikley J., Beesley S., Matthews L., Simpson K.D., Boyce S.H.,
RA Farrow S.N., Else K.J., Singh D., Ray D.W., Loudon A.S.;
RT "The nuclear receptor REV-ERBalpha mediates circadian regulation of innate
RT immunity through selective regulation of inflammatory cytokines.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:582-587(2012).
RN [23]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=23531614; DOI=10.1152/ajpendo.00512.2012;
RA Barclay J.L., Shostak A., Leliavski A., Tsang A.H., Johren O.,
RA Muller-Fielitz H., Landgraf D., Naujokat N., van der Horst G.T., Oster H.;
RT "High-fat diet-induced hyperinsulinemia and tissue-specific insulin
RT resistance in Cry-deficient mice.";
RL Am. J. Physiol. 304:E1053-E1063(2013).
RN [24]
RP INTERACTION WITH CCAR2.
RX PubMed=23398316; DOI=10.1042/bj20121085;
RA Chini C.C., Escande C., Nin V., Chini E.N.;
RT "DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of
RT the nuclear receptor Rev-erbalpha.";
RL Biochem. J. 451:453-461(2013).
RN [25]
RP FUNCTION.
RX PubMed=23201262; DOI=10.1016/j.febslet.2012.11.021;
RA Negoro H., Okinami T., Kanematsu A., Imamura M., Tabata Y., Ogawa O.;
RT "Role of Rev-erbalpha domains for transactivation of the connexin43
RT promoter with Sp1.";
RL FEBS Lett. 587:98-103(2013).
RN [26]
RP FUNCTION.
RX PubMed=24030830; DOI=10.1074/jbc.m113.507038;
RA Xiao J., Zhou Y., Lai H., Lei S., Chi L.H., Mo X.;
RT "Transcription factor NF-Y is a functional regulator of the transcription
RT of core clock gene Bmal1.";
RL J. Biol. Chem. 288:31930-31936(2013).
RN [27]
RP FUNCTION.
RX PubMed=23852339; DOI=10.1038/nm.3213;
RA Woldt E., Sebti Y., Solt L.A., Duhem C., Lancel S., Eeckhoute J.,
RA Hesselink M.K., Paquet C., Delhaye S., Shin Y., Kamenecka T.M., Schaart G.,
RA Lefebvre P., Neviere R., Burris T.P., Schrauwen P., Staels B., Duez H.;
RT "Rev-erb-alpha modulates skeletal muscle oxidative capacity by regulating
RT mitochondrial biogenesis and autophagy.";
RL Nat. Med. 19:1039-1046(2013).
RN [28]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24162845; DOI=10.1038/nature12642;
RA Gerhart-Hines Z., Feng D., Emmett M.J., Everett L.J., Loro E., Briggs E.R.,
RA Bugge A., Hou C., Ferrara C., Seale P., Pryma D.A., Khurana T.S.,
RA Lazar M.A.;
RT "The nuclear receptor Rev-erbalpha controls circadian thermogenic
RT plasticity.";
RL Nature 503:410-413(2013).
RN [29]
RP FUNCTION.
RX PubMed=23728303; DOI=10.1038/nature12209;
RA Lam M.T., Cho H., Lesch H.P., Gosselin D., Heinz S., Tanaka-Oishi Y.,
RA Benner C., Kaikkonen M.U., Kim A.S., Kosaka M., Lee C.Y., Watt A.,
RA Grossman T.R., Rosenfeld M.G., Evans R.M., Glass C.K.;
RT "Rev-Erbs repress macrophage gene expression by inhibiting enhancer-
RT directed transcription.";
RL Nature 498:511-515(2013).
RN [30]
RP FUNCTION.
RX PubMed=23936124; DOI=10.1371/journal.pone.0069939;
RA Vieira E., Marroqui L., Figueroa A.L., Merino B., Fernandez-Ruiz R.,
RA Nadal A., Burris T.P., Gomis R., Quesada I.;
RT "Involvement of the clock gene Rev-erb alpha in the regulation of glucagon
RT secretion in pancreatic alpha-cells.";
RL PLoS ONE 8:E69939-E69939(2013).
RN [31]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=24603368; DOI=10.1038/emm.2013.153;
RA Noh J.Y., Han D.H., Kim M.H., Ko I.G., Kim S.E., Park N., Kyoung Choe H.,
RA Kim K.H., Kim K., Kim C.J., Cho S.;
RT "Presence of multiple peripheral circadian oscillators in the tissues
RT controlling voiding function in mice.";
RL Exp. Mol. Med. 46:E81-E81(2014).
RN [32]
RP FUNCTION.
RX PubMed=24794873; DOI=10.1074/jbc.m114.569723;
RA Aninye I.O., Matsumoto S., Sidhaye A.R., Wondisford F.E.;
RT "Circadian regulation of Tshb gene expression by Rev-Erbalpha (NR1D1) and
RT nuclear corepressor 1 (NCOR1).";
RL J. Biol. Chem. 289:17070-17077(2014).
RN [33]
RP INTERACTION WITH NR0B2.
RX PubMed=25212631; DOI=10.1002/hep.27437;
RA Lee S.M., Zhang Y., Tsuchiya H., Smalling R., Jetten A.M., Wang L.;
RT "Small heterodimer partner/neuronal PAS domain protein 2 axis regulates the
RT oscillation of liver lipid metabolism.";
RL Hepatology 61:497-505(2015).
RN [34]
RP UBIQUITINATION, PROTEASOMAL DEGRADATION, INTERACTION WITH FBXW7 AND CDK1,
RP PHOSPHORYLATION AT THR-275, AND MUTAGENESIS OF THR-275 AND SER-279.
RX PubMed=27238018; DOI=10.1016/j.cell.2016.05.012;
RA Zhao X., Hirota T., Han X., Cho H., Chong L.W., Lamia K., Liu S.,
RA Atkins A.R., Banayo E., Liddle C., Yu R.T., Yates J.R. III, Kay S.A.,
RA Downes M., Evans R.M.;
RT "Circadian amplitude regulation via FBXW7-targeted REV-ERBalpha
RT degradation.";
RL Cell 165:1644-1657(2016).
RN [35]
RP FUNCTION, INTERACTION WITH HSP90AA1 AND HSP90AB1, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=27686098; DOI=10.1242/jcs.190959;
RA Okabe T., Chavan R., Fonseca Costa S.S., Brenna A., Ripperger J.A.,
RA Albrecht U.;
RT "REV-ERBalpha influences the stability and nuclear localization of the
RT glucocorticoid receptor.";
RL J. Cell Sci. 129:4143-4154(2016).
RN [36]
RP LYSOSOME-MEDIATED DEGRADATION.
RX PubMed=29937374; DOI=10.1016/j.cmet.2018.05.023;
RA Toledo M., Batista-Gonzalez A., Merheb E., Aoun M.L., Tarabra E., Feng D.,
RA Sarparanta J., Merlo P., Botre F., Schwartz G.J., Pessin J.E., Singh R.;
RT "Autophagy regulates the liver clock and glucose metabolism by degrading
RT CRY1.";
RL Cell Metab. 28:268-281(2018).
RN [37]
RP FUNCTION, AND INTERACTION WITH NFIL3.
RX PubMed=29653076; DOI=10.1016/j.bcp.2018.04.005;
RA Zhao M., Zhang T., Yu F., Guo L., Wu B.;
RT "E4bp4 regulates carboxylesterase 2 enzymes through repression of the
RT nuclear receptor Rev-erbalpha in mice.";
RL Biochem. Pharmacol. 152:293-301(2018).
RN [38]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION BY CKSN1E.
RX PubMed=29508494; DOI=10.1111/gtc.12571;
RA Ohba Y., Tei H.;
RT "Phosphorylation of N-terminal regions of REV-ERBs regulates their
RT intracellular localization.";
RL Genes Cells 23:285-293(2018).
RN [39]
RP FUNCTION.
RX PubMed=30096135; DOI=10.1371/journal.pbio.2005886;
RA Dyar K.A., Hubert M.J., Mir A.A., Ciciliot S., Lutter D., Greulich F.,
RA Quagliarini F., Kleinert M., Fischer K., Eichmann T.O., Wright L.E.,
RA Pena Paz M.I., Casarin A., Pertegato V., Romanello V., Albiero M.,
RA Mazzucco S., Rizzuto R., Salviati L., Biolo G., Blaauw B., Schiaffino S.,
RA Uhlenhaut N.H.;
RT "Transcriptional programming of lipid and amino acid metabolism by the
RT skeletal muscle circadian clock.";
RL PLoS Biol. 16:E2005886-E2005886(2018).
RN [40]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, UBIQUITINATION,
RP PROTEASOMAL DEGRADATION, AND SUMOYLATION.
RX PubMed=29533925; DOI=10.1172/jci93910;
RA Pariollaud M., Gibbs J.E., Hopwood T.W., Brown S., Begley N., Vonslow R.,
RA Poolman T., Guo B., Saer B., Jones D.H., Tellam J.P., Bresciani S.,
RA Tomkinson N.C., Wojno-Picon J., Cooper A.W., Daniels D.A., Trump R.P.,
RA Grant D., Zuercher W., Willson T.M., MacDonald A.S., Bolognese B.,
RA Podolin P.L., Sanchez Y., Loudon A.S., Ray D.W.;
RT "Circadian clock component REV-ERBalpha controls homeostatic regulation of
RT pulmonary inflammation.";
RL J. Clin. Invest. 128:2281-2296(2018).
RN [41]
RP FUNCTION, AND INTERACTION WITH NR0B2.
RX PubMed=30555544; DOI=10.7150/thno.28676;
RA Zhang T., Yu F., Guo L., Chen M., Yuan X., Wu B.;
RT "Small heterodimer partner regulates circadian cytochromes p450 and drug-
RT induced hepatotoxicity.";
RL Theranostics 8:5246-5258(2018).
RN [42]
RP HEME-BINDING, AND FUNCTION.
RX PubMed=31748741; DOI=10.1038/s41586-019-1774-2;
RA Galmozzi A., Kok B.P., Kim A.S., Montenegro-Burke J.R., Lee J.Y.,
RA Spreafico R., Mosure S., Albert V., Cintron-Colon R., Godio C., Webb W.R.,
RA Conti B., Solt L.A., Kojetin D., Parker C.G., Peluso J.J., Pru J.K.,
RA Siuzdak G., Cravatt B.F., Saez E.;
RT "PGRMC2 is an intracellular haem chaperone critical for adipocyte
RT function.";
RL Nature 576:138-142(2019).
RN [43]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30792350; DOI=10.1073/pnas.1812405116;
RA Griffin P., Dimitry J.M., Sheehan P.W., Lananna B.V., Guo C.,
RA Robinette M.L., Hayes M.E., Cedeno M.R., Nadarajah C.J., Ezerskiy L.A.,
RA Colonna M., Zhang J., Bauer A.Q., Burris T.P., Musiek E.S.;
RT "Circadian clock protein Rev-erbalpha regulates neuroinflammation.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:5102-5107(2019).
CC -!- FUNCTION: Transcriptional repressor which coordinates circadian rhythm
CC and metabolic pathways in a heme-dependent manner. Integral component
CC of the complex transcription machinery that governs circadian
CC rhythmicity and forms a critical negative limb of the circadian clock
CC by directly repressing the expression of core clock components
CC ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic
CC functions, including lipid and bile acid metabolism, adipogenesis,
CC gluconeogenesis and the macrophage inflammatory response. Acts as a
CC receptor for heme which stimulates its interaction with the NCOR1/HDAC3
CC corepressor complex, enhancing transcriptional repression. Recognizes
CC two classes of DNA response elements within the promoter of its target
CC genes and can bind to DNA as either monomers or homodimers, depending
CC on the nature of the response element. Binds as a monomer to a response
CC element composed of the consensus half-site motif 5'-[A/G]GGTCA-3'
CC preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a
CC direct repeat of the core motif spaced by two nucleotides (RevDR-2).
CC Acts as a potent competitive repressor of ROR alpha (RORA) function and
CC regulates the levels of its ligand heme by repressing the expression of
CC PPARGC1A, a potent inducer of heme synthesis. Regulates lipid
CC metabolism by repressing the expression of APOC3 and by influencing the
CC activity of sterol response element binding proteins (SREBPs);
CC represses INSIG2 which interferes with the proteolytic activation of
CC SREBPs which in turn govern the rhythmic expression of enzymes with key
CC functions in sterol and fatty acid synthesis. Regulates gluconeogenesis
CC via repression of G6PC1 and PEPCK and adipocyte differentiation via
CC repression of PPARG. Regulates glucagon release in pancreatic alpha-
CC cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-
CC induced insulin secretion and expression of key lipogenic genes in
CC pancreatic-beta cells. Positively regulates bile acid synthesis by
CC increasing hepatic expression of CYP7A1 via repression of NR0B2 and
CC NFIL3 which are negative regulators of CYP7A1. Modulates skeletal
CC muscle oxidative capacity by regulating mitochondrial biogenesis and
CC autophagy; controls mitochondrial biogenesis and respiration by
CC interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway.
CC Represses the expression of SERPINE1/PAI1, an important modulator of
CC cardiovascular disease and the expression of inflammatory cytokines and
CC chemokines in macrophages. Represses gene expression at a distance in
CC macrophages by inhibiting the transcription of enhancer-derived RNAs
CC (eRNAs). Plays a role in the circadian regulation of body temperature
CC and negatively regulates thermogenic transcriptional programs in brown
CC adipose tissue (BAT); imposes a circadian oscillation in BAT activity,
CC increasing body temperature when awake and depressing thermogenesis
CC during sleep. In concert with NR2E3, regulates transcriptional networks
CC critical for photoreceptor development and function. In addition to its
CC activity as a repressor, can also act as a transcriptional activator.
CC In the ovarian granulosa cells acts as a transcriptional activator of
CC STAR which plays a role in steroid biosynthesis. In collaboration with
CC SP1, activates GJA1 transcription in a heme-independent manner.
CC Represses the transcription of CYP2B10, CYP4A10 and CYP4A14
CC (PubMed:30555544). Represses the transcription of CES2
CC (PubMed:29653076). Represses and regulates the circadian expression of
CC TSHB in a NCOR1-dependent manner (PubMed:24794873). Negatively
CC regulates the protein stability of NR3C1 and influences the time-
CC dependent subcellular distribution of NR3C1, thereby affecting its
CC transcriptional regulatory activity (PubMed:27686098). Plays a critical
CC role in the circadian control of neutrophilic inflammation in the lung;
CC under resting, non-stress conditions, acts as a rhythmic repressor to
CC limit inflammatory activity whereas in the presence of inflammatory
CC triggers undergoes ubiquitin-mediated degradation thereby relieving
CC inhibition of the inflammatory response (PubMed:29533925). Plays a key
CC role in the circadian regulation of microglial activation and
CC neuroinflammation; suppresses microglial activation through the NF-
CC kappaB pathway in the central nervous system (PubMed:30792350). Plays a
CC role in the regulation of the diurnal rhythms of lipid and protein
CC metabolism in the skeletal muscle via transcriptional repression of
CC genes controlling lipid and amino acid metabolism in the muscle
CC (PubMed:30096135). {ECO:0000269|PubMed:18227153,
CC ECO:0000269|PubMed:18454201, ECO:0000269|PubMed:18565334,
CC ECO:0000269|PubMed:19710360, ECO:0000269|PubMed:19721697,
CC ECO:0000269|PubMed:20159955, ECO:0000269|PubMed:21408158,
CC ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:22166979,
CC ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:22474260,
CC ECO:0000269|PubMed:22549838, ECO:0000269|PubMed:23201262,
CC ECO:0000269|PubMed:23728303, ECO:0000269|PubMed:23852339,
CC ECO:0000269|PubMed:23936124, ECO:0000269|PubMed:24030830,
CC ECO:0000269|PubMed:24162845, ECO:0000269|PubMed:24794873,
CC ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29533925,
CC ECO:0000269|PubMed:29653076, ECO:0000269|PubMed:30096135,
CC ECO:0000269|PubMed:30555544, ECO:0000269|PubMed:30792350,
CC ECO:0000269|PubMed:31748741}.
CC -!- SUBUNIT: Binds DNA as a monomer or a homodimer (By similarity).
CC Interacts with NR2E3 and ZNHIT1 (By similarity). Interacts with C1D
CC (PubMed:9405624). Interacts with SP1 (PubMed:22549838). Interacts with
CC OPHN1 (via C-terminus) (PubMed:21874017). Interacts with PER2; the
CC interaction associates PER2 to ARNTL promoter region (PubMed:20159955,
CC PubMed:22170608). Interacts with CRY1 (By similarity). Interacts with
CC CCAR2 (PubMed:23398316). Interacts with SIAH2 (By similarity).
CC Interacts with FBXW7 and CDK1 (PubMed:27238018). Interacts with HUWE1
CC (By similarity). Interacts with NR0B2 (PubMed:25212631,
CC PubMed:30555544). Interacts with NFIL3 (PubMed:29653076). Interacts
CC (via domain NR LBD) with HSP90AA1 and HSP90AB1 (PubMed:27686098).
CC {ECO:0000250|UniProtKB:P20393, ECO:0000269|PubMed:20159955,
CC ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:22170608,
CC ECO:0000269|PubMed:22549838, ECO:0000269|PubMed:23398316,
CC ECO:0000269|PubMed:25212631, ECO:0000269|PubMed:27238018,
CC ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29653076,
CC ECO:0000269|PubMed:30555544, ECO:0000269|PubMed:9405624}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:27686098,
CC ECO:0000269|PubMed:29508494}. Cytoplasm {ECO:0000269|PubMed:21874017,
CC ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29508494}. Cell
CC projection, dendrite {ECO:0000269|PubMed:21874017}. Cell projection,
CC dendritic spine {ECO:0000269|PubMed:21874017}. Note=Localizes to the
CC cytoplasm, dendrites and dendritic spine in the presence of OPHN1
CC (PubMed:21874017). Localizes predominantly to the nucleus at ZT8
CC whereas it is cytoplasmic at ZT20 (PubMed:27686098). Phosphorylation by
CC CSNK1E enhances its cytoplasmic localization (PubMed:29508494).
CC {ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:27686098,
CC ECO:0000269|PubMed:29508494}.
CC -!- TISSUE SPECIFICITY: Expressed during adipocyte differentiation (at
CC protein level). Expressed in skeletal muscle, bladder, lumbar spinal
CC cord, pancreatic islets and hypothalamus. Expressed in developing and
CC adult retina. In the adult retina, predominantly expressed in the outer
CC nuclear layer, where rod and cone cells reside, and also localized to
CC the ganglion cell layer. Expressed in a circadian manner in the liver
CC (PubMed:27686098). Expressed in a circadian manner in the lung with a
CC peak between ZT8 and ZT12 (PubMed:29533925).
CC {ECO:0000269|PubMed:18227153, ECO:0000269|PubMed:18454201,
CC ECO:0000269|PubMed:21408158, ECO:0000269|PubMed:21874017,
CC ECO:0000269|PubMed:22166979, ECO:0000269|PubMed:23531614,
CC ECO:0000269|PubMed:24603368, ECO:0000269|PubMed:27686098,
CC ECO:0000269|PubMed:29533925}.
CC -!- DEVELOPMENTAL STAGE: During development at embryonic day 18.5 dpc,
CC expressed in the outer neuroblastic layer of the retina where
CC developing postmitotic photoreceptors and retinal progenitors reside
CC (at protein level). {ECO:0000269|PubMed:21408158}.
CC -!- INDUCTION: Expression oscillates diurnally in the suprachiasmatic
CC nucleus (SCN) of the hypothalamus as well as in peripheral tissues. In
CC bladder smooth muscle cells, pancreas and lumbar spinal cord, exhibits
CC night/day variations with a peak time at circadian time (CT) 4-12 and a
CC trough at CT16-24. {ECO:0000269|PubMed:14645221,
CC ECO:0000269|PubMed:22549838, ECO:0000269|PubMed:23531614,
CC ECO:0000269|PubMed:24603368}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation
CC (PubMed:20534529). Ubiquitinated by the SCF(FBXW7) complex when
CC phosphorylated by CDK1 leading to its proteasomal degradation
CC (PubMed:27238018). Ubiquitinated by SIAH2; leading to its proteasomal
CC degradation (By similarity). Rapidly ubiquitinated in response to
CC inflammatory triggers and sumoylation is a prerequisite to its
CC ubiquitination (PubMed:29533925). {ECO:0000250|UniProtKB:P20393,
CC ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:27238018,
CC ECO:0000269|PubMed:29533925}.
CC -!- PTM: Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a
CC prerequisite to its ubiquitination. {ECO:0000269|PubMed:29533925}.
CC -!- PTM: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic
CC localization. {ECO:0000269|PubMed:29508494}.
CC -!- PTM: Undergoes lysosome-mediated degradation in a time-dependent manner
CC in the liver. {ECO:0000269|PubMed:29937374}.
CC -!- DISRUPTION PHENOTYPE: Mice display increased cold tolerance, higher
CC oxygen consumption rates, enhanced brown adipose tissue metabolic
CC capacity, maintenance of higher body temperature throughout the light
CC phase and increased glucose uptake only during the day. They also show
CC retinal abnormalities such as pan-retinal spotting and decreased
CC response to light and decreased bile acid accumulation. Double knockout
CC for NR1D1 and PER2 show a significantly shorter period length compared
CC with wild type or single knockouts for both genes. 50% of double
CC knockouts animals show a stable circadian throughout at least 5 weeks
CC in constant darkness. The other 50% of animals lose their circadian
CC rhythmicity when held in constant darkness for an average of 21 days.
CC Animals have blunted steady-state levels of glycogen in the liver in
CC spite of normal patterns of food consumption. Mice show exaggerated
CC pulmonary inflammatory responses (PubMed:29533925). Mice display
CC enhanced spontaneous hippocampal microglial and astrocyte activation,
CC increased microglial NF-kappaB signaling and exacerbated LPS-induced
CC neuroinflammation in the hippocampus (PubMed:30792350). Conditional
CC knockout of both NR1D1 and NR1D2 in bronchiolar epithelial cells
CC abolished diurnal rhythmicity of PER2 in the bronchioles and increased
CC inflammatory responses and chemokine activation (PubMed:29533925).
CC {ECO:0000269|PubMed:20159955, ECO:0000269|PubMed:21408158,
CC ECO:0000269|PubMed:24162845, ECO:0000269|PubMed:29533925,
CC ECO:0000269|PubMed:30792350}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; AK137398; BAE23342.1; -; mRNA.
DR EMBL; AK137582; BAE23418.1; -; mRNA.
DR EMBL; AK146430; BAE27164.1; -; mRNA.
DR EMBL; AK154931; BAE32932.1; -; mRNA.
DR EMBL; AK155597; BAE33339.1; -; mRNA.
DR EMBL; AL590963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008989; AAH08989.1; -; mRNA.
DR EMBL; AF291821; AAG01345.1; -; mRNA.
DR EMBL; X86010; CAA59997.1; -; mRNA.
DR EMBL; AY336125; AAS48348.1; -; Genomic_DNA.
DR CCDS; CCDS25363.1; -.
DR PIR; S52813; S52813.
DR RefSeq; NP_663409.2; NM_145434.4.
DR AlphaFoldDB; Q3UV55; -.
DR SMR; Q3UV55; -.
DR BioGRID; 229856; 3.
DR DIP; DIP-59440N; -.
DR IntAct; Q3UV55; 1.
DR STRING; 10090.ENSMUSP00000069505; -.
DR iPTMnet; Q3UV55; -.
DR PhosphoSitePlus; Q3UV55; -.
DR MaxQB; Q3UV55; -.
DR PaxDb; Q3UV55; -.
DR PeptideAtlas; Q3UV55; -.
DR PRIDE; Q3UV55; -.
DR ProteomicsDB; 295516; -.
DR Antibodypedia; 16433; 505 antibodies from 36 providers.
DR DNASU; 217166; -.
DR Ensembl; ENSMUST00000064941; ENSMUSP00000069505; ENSMUSG00000020889.
DR GeneID; 217166; -.
DR KEGG; mmu:217166; -.
DR UCSC; uc007lhh.2; mouse.
DR CTD; 9572; -.
DR MGI; MGI:2444210; Nr1d1.
DR VEuPathDB; HostDB:ENSMUSG00000020889; -.
DR eggNOG; KOG4846; Eukaryota.
DR GeneTree; ENSGT00940000160548; -.
DR HOGENOM; CLU_007368_2_4_1; -.
DR InParanoid; Q3UV55; -.
DR OMA; LCPTHMY; -.
DR OrthoDB; 1240230at2759; -.
DR PhylomeDB; Q3UV55; -.
DR TreeFam; TF328382; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 217166; 5 hits in 76 CRISPR screens.
DR PRO; PR:Q3UV55; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3UV55; protein.
DR Bgee; ENSMUSG00000020889; Expressed in retinal neural layer and 149 other tissues.
DR Genevisible; Q3UV55; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IDA:MGI.
DR GO; GO:0060086; P:circadian temperature homeostasis; IMP:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0061889; P:negative regulation of astrocyte activation; IMP:UniProtKB.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; IMP:UniProtKB.
DR GO; GO:0150079; P:negative regulation of neuroinflammatory response; IMP:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0070859; P:positive regulation of bile acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0042749; P:regulation of circadian sleep/wake cycle; IMP:UniProtKB.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:2000489; P:regulation of hepatic stellate cell activation; ISO:MGI.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; IMP:UniProtKB.
DR GO; GO:0044321; P:response to leptin; IDA:UniProtKB.
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 Acetylation; Activator; Biological rhythms; Cell projection; Cytoplasm;
KW Differentiation; DNA-binding; Heme; Iron; Metal-binding; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repressor; Synapse;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..615
FT /note="Nuclear receptor subfamily 1 group D member 1"
FT /id="PRO_0000311182"
FT DOMAIN 285..615
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 130..206
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 133..153
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 170..194
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..129
FT /note="Modulating"
FT REGION 1..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..70
FT /note="Required for phosphorylation by CSNK1E and
FT cytoplasmic localization"
FT /evidence="ECO:0000269|PubMed:30792350"
FT REGION 49..285
FT /note="Crucial for activation of GJA1"
FT REGION 235..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..264
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 419
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250"
FT BINDING 603
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250"
FT MOD_RES 55
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P20393"
FT MOD_RES 59
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P20393"
FT MOD_RES 192
FT /note="N6-acetyllysine; by KAT5"
FT /evidence="ECO:0000250"
FT MOD_RES 193
FT /note="N6-acetyllysine; by KAT5"
FT /evidence="ECO:0000250"
FT MOD_RES 275
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:27238018"
FT MOD_RES 592
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P20393"
FT MUTAGEN 275
FT /note="T->A: Loss of interaction with FBXW7 and loss of
FT CDK1-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:27238018"
FT MUTAGEN 279
FT /note="S->A: Loss of interaction with FBXW7."
FT /evidence="ECO:0000269|PubMed:27238018"
FT MUTAGEN 456
FT /note="K->A: Reduces interaction with PER2 by 60%."
FT /evidence="ECO:0000269|PubMed:20159955"
FT CONFLICT 36
FT /note="S -> R (in Ref. 5; CAA59997)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="S -> R (in Ref. 5; CAA59997)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="A -> T (in Ref. 1; BAE27164 and 3; AAH08989)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="F -> L (in Ref. 1; BAE27164)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 615 AA; 66802 MW; FFEC491B616BB326 CRC64;
MTTLDSNNNT GGVITYIGSS GSSPSRTSPE SLYSDSSNGS FQSLTQGCPT YFPPSPTGSL
TQDPARSFGS APPSLSDDSS PSSASSSSSS SSSSFYNGSP PGSLQVAMED SSRVSPSKGT
SNITKLNGMV LLCKVCGDVA SGFHYGVHAC EGCKGFFRRS IQQNIQYKRC LKNENCSIVR
INRNRCQQCR FKKCLSVGMS RDAVRFGRIP KREKQRMLAE MQSAMNLANN QLSSLCPLET
SPTPHPTSGS MGPSPPPAPA PTPLVGFSQF PQQLTPPRSP SPEPTMEDVI SQVARAHREI
FTYAHDKLGT SPGNFNANHA SGSPSATTPH RWESQGCPSA PNDNNLLAAQ RHNEALNGLR
QGPSSYPPTW PSGPTHHSCH QPNSNGHRLC PTHVYSAPEG EAPANSLRQG NTKNVLLACP
MNMYPHGRSG RTVQEIWEDF SMSFTPAVRE VVEFAKHIPG FRDLSQHDQV TLLKAGTFEV
LMVRFASLFN VKDQTVMFLS RTTYSLQELG AMGMGDLLNA MFDFSEKLNS LALTEEELGL
FTAVVLVSAD RSGMENSASV EQLQETLLRA LRALVLKNRP SETSRFTKLL LKLPDLRTLN
NMHSEKLLSF RVDAQ
