PER2_MOUSE
ID PER2_MOUSE Reviewed; 1257 AA.
AC O54943; O54954;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 3.
DT 25-MAY-2022, entry version 167.
DE RecName: Full=Period circadian protein homolog 2;
DE Short=mPER2;
DE AltName: Full=Circadian clock protein PERIOD 2;
GN Name=Per2;
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], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=9428527; DOI=10.1016/s0092-8674(00)80495-x;
RA Albrecht U., Sun Z.S., Eichele G., Lee C.C.;
RT "A differential response of two putative mammalian circadian regulators,
RT mper1 and mper2, to light.";
RL Cell 91:1055-1064(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=9427249; DOI=10.1016/s0896-6273(00)80417-1;
RA Shearman L.P., Zylka M.J., Weaver D.R., Kolakowski L.F. Jr., Reppert S.M.;
RT "Two period homologs: circadian expression and photic regulation in the
RT suprachiasmatic nuclei.";
RL Neuron 19:1261-1269(1997).
RN [3]
RP SEQUENCE REVISION TO 172 AND 501.
RA Zylka M.J., Reppert S.M.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH TIMELESS.
RX PubMed=9856465; DOI=10.1016/s0896-6273(00)80627-3;
RA Sangoram A.M., Saez L., Antoch M.P., Gekakis N., Staknis D., Whiteley A.,
RA Fruechte E.M., Vitaterna M.H., Shimomura K., King D.P., Young M.W.,
RA Weitz C.J., Takahashi J.S.;
RT "Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1
RT interact and negatively regulate CLOCK-ARTNL/BMAL1-induced transcription.";
RL Neuron 21:1101-1113(1998).
RN [5]
RP FUNCTION, INTERACTION WITH PER3; CRY1 AND CRY2, AND SUBCELLULAR LOCATION.
RX PubMed=10428031; DOI=10.1016/s0092-8674(00)81014-4;
RA Kume K., Zylka M.J., Sriram S., Shearman L.P., Weaver D.R., Jin X.,
RA Maywood E.S., Hastings M.H., Reppert S.M.;
RT "mCRY1 and mCRY2 are essential components of the negative limb of the
RT circadian clock feedback loop.";
RL Cell 98:193-205(1999).
RN [6]
RP INTERACTION WITH PER1, AND SUBCELLULAR LOCATION.
RX PubMed=10848614; DOI=10.1128/mcb.20.13.4888-4899.2000;
RA Vielhaber E., Eide E., Rivers A., Gao Z.-H., Virshup D.M.;
RT "Nuclear entry of the circadian regulator mPER1 is controlled by mammalian
RT casein kinase I epsilon.";
RL Mol. Cell. Biol. 20:4888-4899(2000).
RN [7]
RP IDENTIFICATION IN A COMPLEX WITH CLOCK; PER1; PER2; CRY1; CRY2; CSNK1D AND
RP CSNK1E, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=11779462; DOI=10.1016/s0092-8674(01)00610-9;
RA Lee C., Etchegaray J.-P., Cagampang F.R.A., Loudon A.S.I., Reppert S.M.;
RT "Posttranslational mechanisms regulate the mammalian circadian clock.";
RL Cell 107:855-867(2001).
RN [8]
RP SUBCELLULAR LOCATION, AND NUCLEAR EXPORT SIGNAL.
RX PubMed=11591712; DOI=10.1074/jbc.m107726200;
RA Vielhaber E.L., Duricka D., Ullman K.S., Virshup D.M.;
RT "Nuclear export of mammalian PERIOD proteins.";
RL J. Biol. Chem. 276:45921-45927(2001).
RN [9]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, AND DISRUPTION PHENOTYPE.
RX PubMed=11395012; DOI=10.1016/s0896-6273(01)00302-6;
RA Bae K., Jin X., Maywood E.S., Hastings M.H., Reppert S.M., Weaver D.R.;
RT "Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian
RT clock.";
RL Neuron 30:525-536(2001).
RN [10]
RP INTERACTION WITH CRY1, SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, NUCLEAR
RP LOCALIZATION SIGNAL, UBIQUITINATION, AND MUTAGENESIS OF 113-LEU--LEU-116;
RP 464-ILE--LEU-467 AND 985-LEU--LEU-990.
RX PubMed=11889036; DOI=10.1093/emboj/21.6.1301;
RA Yagita K., Tamanini F., Yasuda M., Hoeijmakers J.H., van der Horst G.T.,
RA Okamura H.;
RT "Nucleocytoplasmic shuttling and mCRY-dependent inhibition of
RT ubiquitylation of the mPER2 clock protein.";
RL EMBO J. 21:1301-1314(2002).
RN [11]
RP PHOSPHORYLATION BY CSNK1D AND CKSN1E.
RX PubMed=11865049; DOI=10.1128/mcb.22.6.1693-1703.2002;
RA Akashi M., Tsuchiya Y., Yoshino T., Nishida E.;
RT "Control of intracellular dynamics of mammalian period proteins by casein
RT kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells.";
RL Mol. Cell. Biol. 22:1693-1703(2002).
RN [12]
RP INTERACTION WITH PER1; PER3; CRY1 AND CRY2, AND PHOSPHORYLATION BY CSNK1E.
RX PubMed=14701732; DOI=10.1128/mcb.24.2.584-594.2004;
RA Lee C., Weaver D.R., Reppert S.M.;
RT "Direct association between mouse PERIOD and CKIepsilon is critical for a
RT functioning circadian clock.";
RL Mol. Cell. Biol. 24:584-594(2004).
RN [13]
RP PHOSPHORYLATION AT SER-525; SER-528; SER-531; SER-538; SER-544; THR-554;
RP SER-706; SER-758; SER-763; THR-858; SER-939; THR-964; SER-971 AND SER-1126.
RX PubMed=16097765; DOI=10.1021/ac050232m;
RA Schlosser A., Vanselow J.T., Kramer A.;
RT "Mapping of phosphorylation sites by a multi-protease approach with
RT specific phosphopeptide enrichment and NanoLC-MS/MS analysis.";
RL Anal. Chem. 77:5243-5250(2005).
RN [14]
RP TISSUE SPECIFICITY, INDUCTION BY CIRCADIAN RHYTHMS, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15860628; DOI=10.1126/science.1107373;
RA Brown S.A., Ripperger J., Kadener S., Fleury-Olela F., Vilbois F.,
RA Rosbash M., Schibler U.;
RT "PERIOD1-associated proteins modulate the negative limb of the mammalian
RT circadian oscillator.";
RL Science 308:693-696(2005).
RN [15]
RP FUNCTION IN GLUTAMATE UPTAKE.
RX PubMed=16595674; DOI=10.1074/jbc.m600378200;
RA Yelamanchili S.V., Pendyala G., Brunk I., Darna M., Albrecht U.,
RA Ahnert-Hilger G.;
RT "Differential sorting of the vesicular glutamate transporter 1 into a
RT defined vesicular pool is regulated by light signaling involving the clock
RT gene Period2.";
RL J. Biol. Chem. 281:15671-15679(2006).
RN [16]
RP INTERACTION WITH CLOCK AND ARNTL.
RX PubMed=16717091; DOI=10.1074/jbc.m603722200;
RA Etchegaray J.P., Yang X., DeBruyne J.P., Peters A.H., Weaver D.R.,
RA Jenuwein T., Reppert S.M.;
RT "The polycomb group protein EZH2 is required for mammalian circadian clock
RT function.";
RL J. Biol. Chem. 281:21209-21215(2006).
RN [17]
RP INTERACTION WITH CRY1 AND CRY2.
RX PubMed=16478995; DOI=10.1128/mcb.26.5.1743-1753.2006;
RA Chaves I., Yagita K., Barnhoorn S., Okamura H., van der Horst G.T.J.,
RA Tamanini F.;
RT "Functional evolution of the photolyase/cryptochrome protein family:
RT importance of the C terminus of mammalian CRY1 for circadian core
RT oscillator performance.";
RL Mol. Cell. Biol. 26:1743-1753(2006).
RN [18]
RP FUNCTION IN MAINTENANCE OF CARDIOVASCULAR FUNCTIONS, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17404161; DOI=10.1161/circulationaha.106.653303;
RA Viswambharan H., Carvas J.M., Antic V., Marecic A., Jud C., Zaugg C.E.,
RA Ming X.F., Montani J.P., Albrecht U., Yang Z.;
RT "Mutation of the circadian clock gene Per2 alters vascular endothelial
RT function.";
RL Circulation 115:2188-2195(2007).
RN [19]
RP REVIEW OF FUNCTIONS, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18419266; DOI=10.1101/sqb.2007.72.001;
RA Albrecht U., Bordon A., Schmutz I., Ripperger J.;
RT "The multiple facets of Per2.";
RL Cold Spring Harb. Symp. Quant. Biol. 72:95-104(2007).
RN [20]
RP INTERACTION WITH NFIL3.
RX PubMed=17274955; DOI=10.1016/j.bbrc.2007.01.084;
RA Ohno T., Onishi Y., Ishida N.;
RT "The negative transcription factor E4BP4 is associated with circadian clock
RT protein PERIOD2.";
RL Biochem. Biophys. Res. Commun. 354:1010-1015(2007).
RN [21]
RP FUNCTION.
RX PubMed=17310242; DOI=10.1038/ncb1539;
RA Zhao W.N., Malinin N., Yang F.C., Staknis D., Gekakis N., Maier B.,
RA Reischl S., Kramer A., Weitz C.J.;
RT "CIPC is a mammalian circadian clock protein without invertebrate
RT homologues.";
RL Nat. Cell Biol. 9:268-275(2007).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-693 AND SER-697, AND
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 [23]
RP ACETYLATION, AND DEACETYLATION BY SIRT1.
RX PubMed=18662546; DOI=10.1016/j.cell.2008.06.050;
RA Asher G., Gatfield D., Stratmann M., Reinke H., Dibner C., Kreppel F.,
RA Mostoslavsky R., Alt F.W., Schibler U.;
RT "SIRT1 regulates circadian clock gene expression through PER2
RT deacetylation.";
RL Cell 134:317-328(2008).
RN [24]
RP INTERACTION WITH BTRC AND FBXW11.
RX PubMed=18782782; DOI=10.1093/jb/mvn112;
RA Ohsaki K., Oishi K., Kozono Y., Nakayama K., Nakayama K.I., Ishida N.;
RT "The role of {beta}-TrCP1 and {beta}-TrCP2 in circadian rhythm generation
RT by mediating degradation of clock protein PER2.";
RL J. Biochem. 144:609-618(2008).
RN [25]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, AND INTERACTION WITH ARNTL2.
RX PubMed=19605937; DOI=10.1074/jbc.m109.040758;
RA Sasaki M., Yoshitane H., Du N.H., Okano T., Fukada Y.;
RT "Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its
RT negative role and a positive role of BMAL2 in the circadian
RT transcription.";
RL J. Biol. Chem. 284:25149-25159(2009).
RN [26]
RP FUNCTION IN CIRCADIAN CLOCK, INTERACTION WITH ARNTL AND CLOCK, AND
RP INDUCTION.
RX PubMed=19917250; DOI=10.1016/j.molcel.2009.10.012;
RA Chen R., Schirmer A., Lee Y., Lee H., Kumar V., Yoo S.H., Takahashi J.S.,
RA Lee C.;
RT "Rhythmic PER abundance defines a critical nodal point for negative
RT feedback within the circadian clock mechanism.";
RL Mol. Cell 36:417-430(2009).
RN [27]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION BY CSNK1D AND CSNK1E.
RX PubMed=19414593; DOI=10.1128/mcb.00338-09;
RA Etchegaray J.P., Machida K.K., Noton E., Constance C.M., Dallmann R.,
RA Di Napoli M.N., DeBruyne J.P., Lambert C.M., Yu E.A., Reppert S.M.,
RA Weaver D.R.;
RT "Casein kinase 1 delta regulates the pace of the mammalian circadian
RT clock.";
RL Mol. Cell. Biol. 29:3853-3866(2009).
RN [28]
RP INTERACTION WITH CRY2.
RX PubMed=20840750; DOI=10.1186/1471-2199-11-69;
RA Ozber N., Baris I., Tatlici G., Gur I., Kilinc S., Unal E.B., Kavakli I.H.;
RT "Identification of two amino acids in the C-terminal domain of mouse CRY2
RT essential for PER2 interaction.";
RL BMC Mol. Biol. 11:69-69(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-693 AND SER-697, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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).
RN [30]
RP FUNCTION IN ADIPOGENESIS, INTERACTION WITH PPARG, DISRUPTION PHENOTYPE,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21035761; DOI=10.1016/j.cmet.2010.10.005;
RA Grimaldi B., Bellet M.M., Katada S., Astarita G., Hirayama J., Amin R.H.,
RA Granneman J.G., Piomelli D., Leff T., Sassone-Corsi P.;
RT "PER2 controls lipid metabolism by direct regulation of PPARgamma.";
RL Cell Metab. 12:509-520(2010).
RN [31]
RP FUNCTION AS COACTIVATOR, INTERACTION WITH ARNTL; CRY1; HNF4A; NR1D1; NR4A2;
RP RORA; PPARA AND THRA, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 306-LEU--LEU-310 AND 1052-ASN--LEU-1055.
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 [32]
RP INTERACTION WITH ARNTL; CLOCK AND CRY1.
RX PubMed=21613214; DOI=10.1074/jbc.m111.254680;
RA Ye R., Selby C.P., Ozturk N., Annayev Y., Sancar A.;
RT "Biochemical analysis of the canonical model for the mammalian circadian
RT clock.";
RL J. Biol. Chem. 286:25891-25902(2011).
RN [33]
RP FUNCTION.
RX PubMed=21768648; DOI=10.1074/jbc.m111.258970;
RA Koyanagi S., Hamdan A.M., Horiguchi M., Kusunose N., Okamoto A.,
RA Matsunaga N., Ohdo S.;
RT "cAMP-response element (CRE)-mediated transcription by activating
RT transcription factor-4 (ATF4) is essential for circadian expression of the
RT Period2 gene.";
RL J. Biol. Chem. 286:32416-32423(2011).
RN [34]
RP INTERACTION WITH MAGEL2, AND SUBCELLULAR LOCATION.
RX PubMed=22208286; DOI=10.1186/1740-3391-9-12;
RA Devos J., Weselake S.V., Wevrick R.;
RT "Magel2, a Prader-Willi syndrome candidate gene, modulates the activities
RT of circadian rhythm proteins in cultured cells.";
RL J. Circadian. Rhythms. 9:12-12(2011).
RN [35]
RP SUBCELLULAR LOCATION, AND DEPHOSPHORYLATION.
RX PubMed=21712997; DOI=10.1371/journal.pone.0021325;
RA Schmutz I., Wendt S., Schnell A., Kramer A., Mansuy I.M., Albrecht U.;
RT "Protein phosphatase 1 (PP1) is a post-translational regulator of the
RT mammalian circadian clock.";
RL PLoS ONE 6:E21325-E21325(2011).
RN [36]
RP FUNCTION IN CIRCADIAN CLOCK, PHOSPHORYLATION BY CSNK1D AND CKSN1E, AND
RP SUBCELLULAR LOCATION.
RX PubMed=21930935; DOI=10.1073/pnas.1107178108;
RA Lee H.M., Chen R., Kim H., Etchegaray J.P., Weaver D.R., Lee C.;
RT "The period of the circadian oscillator is primarily determined by the
RT balance between casein kinase 1 and protein phosphatase 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:16451-16456(2011).
RN [37]
RP FUNCTION IN HISTONE DEACETYLATION, INTERACTION WITH ARNTL1; CLOCK; CRY1;
RP CSNK1E; PER1, AND IDENTIFICATION IN A COMPLEX WITH SFPQ AND SIN3A.
RX PubMed=21680841; DOI=10.1126/science.1196766;
RA Duong H.A., Robles M.S., Knutti D., Weitz C.J.;
RT "A molecular mechanism for circadian clock negative feedback.";
RL Science 332:1436-1439(2011).
RN [38]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=22274616; DOI=10.1038/emboj.2012.1;
RA Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A.,
RA Zhao Z., Lee C.C., Chang K.S.;
RT "PML regulates PER2 nuclear localization and circadian function.";
RL EMBO J. 31:1427-1439(2012).
RN [39]
RP INTERACTION WITH CAVIN3 AND CRY2.
RX PubMed=23079727; DOI=10.1038/embor.2012.158;
RA Schneider K., Kocher T., Andersin T., Kurzchalia T., Schibler U.,
RA Gatfield D.;
RT "CAVIN-3 regulates circadian period length and PER:CRY protein abundance
RT and interactions.";
RL EMBO Rep. 13:1138-1144(2012).
RN [40]
RP FUNCTION IN INSULIN SECRETION, AND DISRUPTION PHENOTYPE.
RX PubMed=22504074; DOI=10.1016/j.febslet.2012.03.034;
RA Zhao Y., Zhang Y., Zhou M., Wang S., Hua Z., Zhang J.;
RT "Loss of mPer2 increases plasma insulin levels by enhanced glucose-
RT stimulated insulin secretion and impaired insulin clearance in mice.";
RL FEBS Lett. 586:1306-1311(2012).
RN [41]
RP INTERACTION WITH SFPQ AND NONO.
RX PubMed=22966205; DOI=10.1128/mcb.00334-12;
RA Kowalska E., Ripperger J.A., Muheim C., Maier B., Kurihara Y., Fox A.H.,
RA Kramer A., Brown S.A.;
RT "Distinct roles of DBHS family members in the circadian transcriptional
RT feedback loop.";
RL Mol. Cell. Biol. 32:4585-4594(2012).
RN [42]
RP FUNCTION IN TRANSCTIPIONAL TERMINATION INHIBITION, IDENTIFICATION IN A
RP COMPLEX WITH CDK9; DDX5; DHX9; NCBP1 AND POLR2A, INTERACTION WITH SETX, AND
RP RNA-BINDING.
RX PubMed=22767893; DOI=10.1126/science.1221592;
RA Padmanabhan K., Robles M.S., Westerling T., Weitz C.J.;
RT "Feedback regulation of transcriptional termination by the mammalian
RT circadian clock PERIOD complex.";
RL Science 337:599-602(2012).
RN [43]
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 [44]
RP TISSUE SPECIFICITY.
RX PubMed=24154698; DOI=10.1152/ajprenal.00472.2013;
RA Richards J., Cheng K.Y., All S., Skopis G., Jeffers L., Lynch I.J.,
RA Wingo C.S., Gumz M.L.;
RT "A role for the circadian clock protein Per1 in the regulation of
RT aldosterone levels and renal Na+ retention.";
RL Am. J. Physiol. 305:F1697-F1704(2013).
RN [45]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CRY1.
RX PubMed=23418588; DOI=10.1371/journal.pone.0056623;
RA Engelen E., Janssens R.C., Yagita K., Smits V.A., van der Horst G.T.,
RA Tamanini F.;
RT "Mammalian TIMELESS is involved in period determination and DNA damage-
RT dependent phase advancing of the circadian clock.";
RL PLoS ONE 8:E56623-E56623(2013).
RN [46]
RP FUNCTION IN CARDIAC METABOLISM REGULATION, AND DISRUPTION PHENOTYPE.
RX PubMed=23977055; DOI=10.1371/journal.pone.0071493;
RA Bonney S., Kominsky D., Brodsky K., Eltzschig H., Walker L., Eckle T.;
RT "Cardiac Per2 functions as novel link between fatty acid metabolism and
RT myocardial inflammation during ischemia and reperfusion injury of the
RT heart.";
RL PLoS ONE 8:E71493-E71493(2013).
RN [47]
RP REVIEW.
RX PubMed=23303907; DOI=10.1152/physrev.00016.2012;
RA Eckel-Mahan K., Sassone-Corsi P.;
RT "Metabolism and the circadian clock converge.";
RL Physiol. Rev. 93:107-135(2013).
RN [48]
RP INDUCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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 [49]
RP INTERACTION WITH CIART.
RX PubMed=24385426; DOI=10.1074/jbc.m113.534651;
RA Annayev Y., Adar S., Chiou Y.Y., Lieb J., Sancar A., Ye R.;
RT "Gene model 129 (Gm129) encodes a novel transcriptional repressor that
RT modulates circadian gene expression.";
RL J. Biol. Chem. 289:5013-5024(2014).
RN [50]
RP FUNCTION IN HISTONE METHYLATION, AND IDENTIFICATION IN A COMPLEX WITH CRY1;
RP CSNK1E; HDAC1; CBX3; SUV39H1; SUV39H2 AND TRIM28.
RX PubMed=24413057; DOI=10.1038/nsmb.2746;
RA Duong H.A., Weitz C.J.;
RT "Temporal orchestration of repressive chromatin modifiers by circadian
RT clock Period complexes.";
RL Nat. Struct. Mol. Biol. 21:126-132(2014).
RN [51]
RP REVIEW.
RX PubMed=23916625; DOI=10.1016/j.tcb.2013.07.002;
RA Partch C.L., Green C.B., Takahashi J.S.;
RT "Molecular architecture of the mammalian circadian clock.";
RL Trends Cell Biol. 24:90-99(2014).
RN [52]
RP INTERACTION WITH MAP1LC3B.
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 [53]
RP ACETYLATION, AND DEACETYLATION BY SIRT6.
RX PubMed=30782483; DOI=10.1016/j.bbrc.2019.01.143;
RA Sun S., Liu Z., Feng Y., Shi L., Cao X., Cai Y., Liu B.;
RT "Sirt6 deacetylase activity regulates circadian rhythms via Per2.";
RL Biochem. Biophys. Res. Commun. 511:234-238(2019).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 170-473, MUTAGENESIS OF PHE-415;
RP TRP-419 AND ILE-427, AND SUBUNIT.
RX PubMed=19402751; DOI=10.1371/journal.pbio.1000094;
RA Hennig S., Strauss H.M., Vanselow K., Yildiz O., Schulze S., Arens J.,
RA Kramer A., Wolf E.;
RT "Structural and functional analyses of PAS domain interactions of the clock
RT proteins Drosophila PERIOD and mouse PERIOD2.";
RL PLoS Biol. 7:E94-E94(2009).
CC -!- FUNCTION: Transcriptional repressor which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic syndrome
CC and aging. A transcription/translation feedback loop (TTFL) forms the
CC core of the molecular circadian clock mechanism. Transcription factors,
CC CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb
CC of the feedback loop, act in the form of a heterodimer and activate the
CC transcription of core clock genes and clock-controlled genes (involved
CC in key metabolic processes), harboring E-box elements (5'-CACGTG-3')
CC within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which
CC are transcriptional repressors form the negative limb of the feedback
CC loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2
CC heterodimer inhibiting its activity and thereby negatively regulating
CC their own expression. This heterodimer also activates nuclear receptors
CC NR1D1/2 and RORA/B/G, which form a second feedback loop and which
CC activate and repress ARNTL/BMAL1 transcription, respectively. PER1 and
CC PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate
CC circadian timing, but also contribute directly to repression of clock-
CC controlled target genes through interaction with several classes of
CC RNA-binding proteins, helicases and others transcriptional repressors.
CC PER appears to regulate circadian control of transcription by at least
CC three different modes. First, interacts directly with the CLOCK-
CC ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit
CC complexes containing the SIN3-HDAC that remodel chromatin to repress
CC transcription. Second, brings H3K9 methyltransferases such as SUV39H1
CC and SUV39H2 to the E-box elements of the circadian target genes, like
CC PER2 itself or PER1. The recruitment of each repressive modifier to the
CC DNA seems to be very precisely temporally orchestrated by the large PER
CC complex, the deacetylases acting before than the methyltransferases.
CC Additionally, large PER complexes are also recruited to the target
CC genes 3' termination site through interactions with RNA-binding
CC proteins and helicases that may play a role in transcription
CC termination to regulate transcription independently of CLOCK-
CC ARTNL/BMAL1 interactions. Recruitment of large PER complexes to the
CC elongating polymerase at PER and CRY termination sites inhibited SETX
CC action, impeding RNA polymerase II release and thereby repressing
CC transcriptional reinitiation. May propagate clock information to
CC metabolic pathways via the interaction with nuclear receptors.
CC Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at
CC the promoter of nuclear receptors target genes like ARNTL or G6PC1.
CC Directly and specifically represses PPARG proadipogenic activity by
CC blocking PPARG recruitment to target promoters and thereby
CC transcriptional activation. Required for fatty acid and lipid
CC metabolism, is involved as well in the regulation of circulating
CC insulin levels. Plays an important role in the maintenance of
CC cardiovascular functions through the regulation of NO and
CC vasodilatatory prostaglandins production in aortas. Controls circadian
CC glutamate uptake in synaptic vesicles through the regulation of VGLUT1
CC expression. May also be involved in the regulation of inflammatory
CC processes. Represses the CLOCK-ARNTL/BMAL1 induced transcription of
CC BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the
CC TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1.
CC {ECO:0000269|PubMed:10428031, ECO:0000269|PubMed:11395012,
CC ECO:0000269|PubMed:16595674, ECO:0000269|PubMed:17310242,
CC ECO:0000269|PubMed:17404161, ECO:0000269|PubMed:19605937,
CC ECO:0000269|PubMed:19917250, ECO:0000269|PubMed:20159955,
CC ECO:0000269|PubMed:21035761, ECO:0000269|PubMed:21680841,
CC ECO:0000269|PubMed:21768648, ECO:0000269|PubMed:21930935,
CC ECO:0000269|PubMed:22504074, ECO:0000269|PubMed:22767893,
CC ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:23977055,
CC ECO:0000269|PubMed:24413057}.
CC -!- SUBUNIT: Homodimer. Component of the circadian core oscillator, which
CC includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2,
CC CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:11779462).
CC Interacts with CLOCK-ARNTL/BMAL1 (off DNA). Interacts with
CC ARNTL2/BMAL2. Interacts directly with PER1 and PER3, and through a C-
CC terminal domain, with CRY1 and CRY2. Interacts, via its second PAS
CC domain, with TIMELESS in vitro. Interacts with NFIL3. Different large
CC complexes have been identified with different repressive functions. The
CC core of PER complexes is composed of at least PER1, PER2, PER3, CRY1,
CC CRY2, CSNK1D and/or CSNK1E. The large PER complex involved in the
CC repression of transcriptional termination is composed of at least PER2,
CC CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). The large PER complex
CC involved in the histone deacetylation is composed of at least HDAC1,
CC PER2, SFPQ and SIN3A. The large PER complex involved in the histone
CC methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or
CC SUV39H2; CBX3 mediates the formation of the complex. Interacts with
CC SETX; the interaction inhibits termination of circadian target genes.
CC Interacts with the nuclear receptors HNF4A, NR1D1, NR4A2, RORA, PPARA,
CC PPARG and THRA; the interaction with at least PPARG is ligand
CC dependent. Interacts with PML. Interacts (phosphorylated) with BTRC and
CC FBXW11; the interactions trigger proteasomal degradation. Interacts
CC with NONO and SFPQ. Interacts with CAVIN3. Interacts with MAGEL2.
CC Interacts with MAP1LC3B (PubMed:29937374). Interacts with HNF4A (By
CC similarity). {ECO:0000250|UniProtKB:O15055,
CC ECO:0000269|PubMed:10428031, ECO:0000269|PubMed:10848614,
CC ECO:0000269|PubMed:11779462, ECO:0000269|PubMed:11889036,
CC ECO:0000269|PubMed:14701732, ECO:0000269|PubMed:16478995,
CC ECO:0000269|PubMed:17274955, ECO:0000269|PubMed:18662546,
CC ECO:0000269|PubMed:18782782, ECO:0000269|PubMed:19402751,
CC ECO:0000269|PubMed:19605937, ECO:0000269|PubMed:19917250,
CC ECO:0000269|PubMed:20159955, ECO:0000269|PubMed:20840750,
CC ECO:0000269|PubMed:21035761, ECO:0000269|PubMed:21613214,
CC ECO:0000269|PubMed:21680841, ECO:0000269|PubMed:22208286,
CC ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:22767893,
CC ECO:0000269|PubMed:22966205, ECO:0000269|PubMed:23079727,
CC ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:24385426,
CC ECO:0000269|PubMed:24413057, ECO:0000269|PubMed:29937374,
CC ECO:0000269|PubMed:9856465}.
CC -!- INTERACTION:
CC O54943; Q9WTL8: Arntl; NbExp=9; IntAct=EBI-1266779, EBI-644534;
CC O54943; Q91VJ2: Cavin3; NbExp=4; IntAct=EBI-1266779, EBI-8094261;
CC O54943; Q3TQ03: Ciart; NbExp=2; IntAct=EBI-1266779, EBI-16101489;
CC O54943; O08785: Clock; NbExp=10; IntAct=EBI-1266779, EBI-79859;
CC O54943; P97784: Cry1; NbExp=22; IntAct=EBI-1266779, EBI-1266607;
CC O54943; Q9R194: Cry2; NbExp=8; IntAct=EBI-1266779, EBI-1266619;
CC O54943; Q9JMK2: Csnk1e; NbExp=4; IntAct=EBI-1266779, EBI-771709;
CC O54943; Q8C4V4: Fbxl3; NbExp=2; IntAct=EBI-1266779, EBI-1266589;
CC O54943; O35973: Per1; NbExp=5; IntAct=EBI-1266779, EBI-1266764;
CC O54943; O54943: Per2; NbExp=6; IntAct=EBI-1266779, EBI-1266779;
CC O54943; Q60953: Pml; NbExp=4; IntAct=EBI-1266779, EBI-3895605;
CC O54943; Q8N365: CIART; Xeno; NbExp=4; IntAct=EBI-1266779, EBI-10265133;
CC O54943; P20393: NR1D1; Xeno; NbExp=2; IntAct=EBI-1266779, EBI-2811738;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11889036,
CC ECO:0000269|PubMed:22208286}. Cytoplasm {ECO:0000269|PubMed:11889036,
CC ECO:0000269|PubMed:22208286}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:22274616}. Note=Nucleocytoplasmic shuttling is
CC effected by interaction with other circadian core oscillator proteins
CC and/or by phosphorylation. Translocate to the nucleus after
CC phosphorylation by CSNK1D or CSNK1E. Also translocated to the nucleus
CC by CRY1 or CRY2. PML regulates its nuclear localization
CC (PubMed:22274616). {ECO:0000269|PubMed:22274616}.
CC -!- TISSUE SPECIFICITY: In the brain, high expression in SCN during the
CC subjective day. Constitutive expression in the cornu ammonis and in the
CC dentate gyrus of the hippocampus. Also expressed in the piriform cortex
CC and the glomeruli of the olfactory bulb, and at a lower extent in the
CC cerebral cortex. Not expressed in the pars tuberalis and the Purkinje
CC neurons. Also expressed in adipose tissue (white and brown), heart,
CC kidney, bladder, lumbar spinal cord, skeletal muscle, spleen, lung,
CC pancreas and liver with highest levels in skeletal muscle and liver and
CC lowest levels in spleen. {ECO:0000269|PubMed:15860628,
CC ECO:0000269|PubMed:21035761, ECO:0000269|PubMed:23531614,
CC ECO:0000269|PubMed:24154698, ECO:0000269|PubMed:24603368,
CC ECO:0000269|PubMed:9427249, ECO:0000269|PubMed:9428527}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the SCN during late fetal and early
CC neonatal life. Expression increases during adipogenesis.
CC {ECO:0000269|PubMed:21035761, ECO:0000269|PubMed:9427249}.
CC -!- INDUCTION: Oscillates diurnally in several tissues, mainly in central
CC nervous system and liver (at protein levels) but also in pancreas,
CC bladder and lumbar spinal cord. Rhythmic levels are critical for the
CC generation of circadian rhythms in central as well as peripheral
CC clocks. Targeted degradation of PER and CRY proteins enables the
CC reactivation of CLOCK-ARTNL/BMAL1, thus initiating a new circadian
CC transcriptional cycle with an intrinsic period of 24 hours.
CC {ECO:0000269|PubMed:15860628, ECO:0000269|PubMed:18419266,
CC ECO:0000269|PubMed:19917250, ECO:0000269|PubMed:23531614,
CC ECO:0000269|PubMed:24603368, ECO:0000269|PubMed:9427249,
CC ECO:0000269|PubMed:9428527}.
CC -!- PTM: Acetylated (PubMed:18662546, PubMed:30782483). Deacetylated by
CC SIRT1, resulting in decreased protein stability (PubMed:18662546).
CC Deacetylated by SIRT6, preventing its degradation by the proteasome,
CC resulting in increased protein stability (PubMed:30782483).
CC {ECO:0000269|PubMed:18662546, ECO:0000269|PubMed:30782483}.
CC -!- PTM: Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in
CC PER2 protein degradation. May be dephosphorylated by PP1.
CC {ECO:0000269|PubMed:11865049, ECO:0000269|PubMed:14701732,
CC ECO:0000269|PubMed:16097765, ECO:0000269|PubMed:19414593,
CC ECO:0000269|PubMed:21930935}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC Ubiquitination may be inhibited by CRY1. {ECO:0000269|PubMed:11889036}.
CC -!- DISRUPTION PHENOTYPE: Animals show severely disrupted circadian
CC behavior. During myocardial ischemia, they have larger infarct sizes
CC with deficient lactate production. Mice show reduced muscle strength
CC under stress conditions, show endothelial dysfunctions and have a mean
CC arterial pressure significantly lower compared to wild types. They have
CC elevated circulatory insulin levels associated with enhanced glucose-
CC stimulated insulin secretion and impaired insulin clearance. Animals
CC also have increased levels of liver glycogen and impaired hepatic
CC gluconeogenesis. They display altered lipid metabolism with drastic
CC reduction of total triacylglycerides and non-esterified fatty acids.
CC Double knockouts for PER2 and PER1 show an abrupt loss of rhythmicity
CC immediately upon transfer to exposure to constant darkness. Animals
CC have largely affected the water intake (polydipsia) and urine volume
CC (polyuria). Double knocknouts for PER2 and PER3 show the same phenotype
CC as PER2 simple knockouts. Double knockout for NR1D1 and PER2 show a
CC significantly shorter period length compared with wild type or single
CC knockouts for both genes. 50% of double knockouts animals show a stable
CC circadian throughout at least 5 weeks in constant darkness. The other
CC 50% of animals lose their circadian rhythmicity when held in constant
CC darkness for an average of 21 days. Animals have blunted steady-state
CC levels of glycogen in the liver in spite of normal patterns of food
CC consumption. {ECO:0000269|PubMed:11395012, ECO:0000269|PubMed:17404161,
CC ECO:0000269|PubMed:18419266, ECO:0000269|PubMed:20159955,
CC ECO:0000269|PubMed:21035761, ECO:0000269|PubMed:22504074,
CC ECO:0000269|PubMed:23977055, ECO:0000269|PubMed:24603368}.
CC ---------------------------------------------------------------------------
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DR EMBL; AF036893; AAC39942.1; -; mRNA.
DR EMBL; AF035830; AAC53592.1; -; mRNA.
DR CCDS; CCDS35663.1; -.
DR PIR; T09493; T09493.
DR RefSeq; NP_035196.2; NM_011066.3.
DR PDB; 3GDI; X-ray; 2.40 A; A/B=170-473.
DR PDB; 4CT0; X-ray; 2.45 A; B=1132-1252.
DR PDB; 4U8H; X-ray; 2.80 A; B/D=1095-1215.
DR PDBsum; 3GDI; -.
DR PDBsum; 4CT0; -.
DR PDBsum; 4U8H; -.
DR AlphaFoldDB; O54943; -.
DR SMR; O54943; -.
DR BioGRID; 202112; 31.
DR ComplexPortal; CPX-3209; Cry1-Per2 complex.
DR ComplexPortal; CPX-3210; Cry2-Per2 complex.
DR CORUM; O54943; -.
DR DIP; DIP-38518N; -.
DR ELM; O54943; -.
DR IntAct; O54943; 38.
DR MINT; O54943; -.
DR STRING; 10090.ENSMUSP00000066620; -.
DR iPTMnet; O54943; -.
DR PhosphoSitePlus; O54943; -.
DR PaxDb; O54943; -.
DR PRIDE; O54943; -.
DR ProteomicsDB; 288029; -.
DR DNASU; 18627; -.
DR GeneID; 18627; -.
DR KEGG; mmu:18627; -.
DR CTD; 8864; -.
DR MGI; MGI:1195265; Per2.
DR eggNOG; KOG3753; Eukaryota.
DR InParanoid; O54943; -.
DR OrthoDB; 145617at2759; -.
DR PhylomeDB; O54943; -.
DR TreeFam; TF318445; -.
DR BioGRID-ORCS; 18627; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Per2; mouse.
DR EvolutionaryTrace; O54943; -.
DR PRO; PR:O54943; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O54943; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; 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; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:1990226; F:histone methyltransferase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:UniProtKB.
DR GO; GO:0036002; F:pre-mRNA binding; IDA:UniProtKB.
DR GO; GO:0070063; F:RNA polymerase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0097167; P:circadian regulation of translation; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IDA:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; IMP:UniProtKB.
DR GO; GO:0019249; P:lactate biosynthetic process; IMP:UniProtKB.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:0060567; P:negative regulation of DNA-templated transcription, termination; IDA:UniProtKB.
DR GO; GO:0070345; P:negative regulation of fat cell proliferation; IMP:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0051946; P:regulation of glutamate uptake involved in transmission of nerve impulse; IMP:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0019229; P:regulation of vasoconstriction; IMP:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IMP:UniProtKB.
DR GO; GO:0050872; P:white fat cell differentiation; IMP:UniProtKB.
DR CDD; cd00130; PAS; 1.
DR IDEAL; IID50265; -.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013655; PAS_fold_3.
DR InterPro; IPR022728; Period_circadian-like_C.
DR Pfam; PF08447; PAS_3; 1.
DR Pfam; PF12114; Period_C; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Biological rhythms; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..1257
FT /note="Period circadian protein homolog 2"
FT /id="PRO_0000162631"
FT DOMAIN 179..246
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 319..385
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 393..436
FT /note="PAC"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..482
FT /note="Important for protein stability"
FT /evidence="ECO:0000250|UniProtKB:Q9Z301"
FT REGION 510..709
FT /note="CSNK1E binding domain"
FT /evidence="ECO:0000269|PubMed:14701732"
FT REGION 617..638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..832
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 882..1067
FT /note="Interaction with PPARG"
FT /evidence="ECO:0000269|PubMed:21035761"
FT REGION 994..1044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1070..1115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1157..1257
FT /note="CRY binding domain"
FT /evidence="ECO:0000250|UniProtKB:Q9Z301"
FT REGION 1224..1257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 109..118
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000269|PubMed:11889036"
FT MOTIF 306..310
FT /note="LXXLL"
FT MOTIF 460..469
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000269|PubMed:11889036"
FT MOTIF 778..794
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:11889036"
FT MOTIF 983..990
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000269|PubMed:11889036"
FT MOTIF 1051..1055
FT /note="LXXLL"
FT COMPBIAS 28..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 475..502
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..777
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..832
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1000..1044
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1070..1114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 544
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 554
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15055"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 706
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 758
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 763
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 858
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 964
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 971
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MOD_RES 1126
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16097765"
FT MUTAGEN 113..116
FT /note="LKEL->AKEA: Accumulates in the nucleus. Exlcusively
FT nuclear; when associated with 464-A--A-467 and 985-A--A-
FT 990."
FT /evidence="ECO:0000269|PubMed:11889036"
FT MUTAGEN 306..310
FT /note="LCCLL->ACCAA: Abolishes interaction with PPARA and
FT NR1D1. No effect on interaction with CRY1. Abolishes
FT interaction with PPARA and NR1D1 as well as reduces the
FT amplitude of ARNTL expression; when associated with 1052-
FT E--A-1055."
FT /evidence="ECO:0000269|PubMed:20159955"
FT MUTAGEN 306..310
FT /note="Missing: Abolishes interaction with NR1D1."
FT /evidence="ECO:0000269|PubMed:20159955"
FT MUTAGEN 415
FT /note="F->E: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:19402751"
FT MUTAGEN 419
FT /note="W->E: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:19402751"
FT MUTAGEN 427
FT /note="I->E: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:19402751"
FT MUTAGEN 464..467
FT /note="IHRL->AHRA: Accumulates in the nucleus. Exlcusively
FT nuclear; when associated with 113-A--A-116 and 985-A--A-
FT 990."
FT /evidence="ECO:0000269|PubMed:11889036"
FT MUTAGEN 985..990
FT /note="LNLLQL->ANAAQA: Slightly accumulates in the nucleus.
FT Exlcusively nuclear; when associated with 464-A--A-467 and
FT 985-A--A-990."
FT /evidence="ECO:0000269|PubMed:11889036"
FT MUTAGEN 1052..1055
FT /note="NLLL->EAAA: No effect on interaction with PPARA.
FT Abolishes interaction with PPARA and NR1D1 as well as
FT reduces the amplitude of ARNTL expression; when associated
FT with 306-A--A-310."
FT /evidence="ECO:0000269|PubMed:20159955"
FT MUTAGEN 1052..1055
FT /note="Missing: No effect on interaction with NR1D1."
FT /evidence="ECO:0000269|PubMed:20159955"
FT CONFLICT 445
FT /note="P -> S (in Ref. 2; AAC53592)"
FT /evidence="ECO:0000305"
FT CONFLICT 728
FT /note="K -> R (in Ref. 2; AAC53592)"
FT /evidence="ECO:0000305"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:3GDI"
FT TURN 197..199
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:3GDI"
FT TURN 207..212
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 225..228
FT /evidence="ECO:0007829|PDB:3GDI"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 234..240
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 285..295
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 306..314
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 330..335
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 348..352
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 356..359
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 364..367
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 373..385
FT /evidence="ECO:0007829|PDB:3GDI"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 391..399
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 405..416
FT /evidence="ECO:0007829|PDB:3GDI"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 423..434
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:3GDI"
FT HELIX 455..467
FT /evidence="ECO:0007829|PDB:3GDI"
FT STRAND 1132..1135
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1138..1141
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1147..1152
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1160..1174
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1175..1177
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1183..1189
FT /evidence="ECO:0007829|PDB:4CT0"
FT TURN 1190..1192
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1195..1198
FT /evidence="ECO:0007829|PDB:4CT0"
FT HELIX 1203..1205
FT /evidence="ECO:0007829|PDB:4CT0"
FT STRAND 1207..1209
FT /evidence="ECO:0007829|PDB:4CT0"
FT TURN 1211..1213
FT /evidence="ECO:0007829|PDB:4CT0"
SQ SEQUENCE 1257 AA; 135881 MW; 554B8AFF036CF7FB CRC64;
MNGYVDFSPS PTSPTKEPGA PQPTQAVLQE DVDMSSGSSG NENCSTGRDS QGSDCDDNGK
ELRMLVESSN THPSPDDAFR LMMTEAEHNP STSGCSSEQS AKADAHKELI RTLKELKVHL
PADKKAKGKA STLATLKYAL RSVKQVKANE EYYQLLMSSE SQPCSVDVPS YSMEQVEGIT
SEYIVKNADM FAVAVSLVSG KILYISNQVA SIFHCKKDAF SDAKFVEFLA PHDVSVFHSY
TTPYKLPPWS VCSGLDSFTQ ECMEEKSFFC RVSVGKHHEN EIRYQPFRMT PYLVKVQEQQ
GAESQLCCLL LAERVHSGYE APRIPPEKRI FTTTHTPNCL FQAVDERAVP LLGYLPQDLI
ETPVLVQLHP SDRPLMLAIH KKILQAGGQP FDYSPIRFRT RNGEYITLDT SWSSFINPWS
RKISFIIGRH KVRVGPLNED VFAAPPCPEE KTPHPSVQEL TEQIHRLLMQ PVPHSGSSGY
GSLGSNGSHE HLMSQTSSSD SNGQEESHRR RSGIFKTSGK IQTKSHVSHE SGGQKEASVA
EMQSSPPAQV KAVTTIERDS SGASLPKASF PEELAYKNQP PCSYQQISCL DSVIRYLESC
SEAATLKRKC EFPANIPSRK ATVSPGLHSG EAARPSKVTS HTEVSAHLSS LTLPGKAESV
VSLTSQCSYS STIVHVGDKK PQPELETVED MASGPESLDG AAGGLSQEKG PLQKLGLTKE
VLAAHTQKEE QGFLQRFREV SRLSALQAHC QNYLQERSRA QASDRGLRNT SGLESSWKKT
GKNRKLKSKR VKTRDSSEST GSGGPVSHRP PLMGLNATAW SPSDTSQSSC PSAPFPTAVP
AYPLPVFQAP GIVSTPGTVV APPAATHTGF TMPVVPMGTQ PEFAVQPLPF AAPLAPVMAF
MLPSYPFPPA TPNLPQAFLP SQPHFPAHPT LASEITPASQ AEFPSRTSTL RQPCACPVTP
PAGTVALGRA SPPLFQSRGS SPLQLNLLQL EEAPEGSTGA AGTLGTTGTA ASGLDCTSGT
SRDRQPKAPP TCNEPSDTQN SDAISTSSDL LNLLLGEDLC SATGSALSRS GASATSDSLG
SSSLGFGTSQ SGAGSSDTSH TSKYFGSIDS SENNHKAKMI PDTEESEQFI KYVLQDPIWL
LMANTDDSIM MTYQLPSRDL QAVLKEDQEK LKLLQRSQPR FTEGQRRELR EVHPWVHTGG
LPTAIDVTGC VYCESEEKGN ICLPYEEDSP SPGLCDTSEA KEEEGEQLTG PRIEAQT
