PER1_MOUSE
ID PER1_MOUSE Reviewed; 1291 AA.
AC O35973; B1ASX0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Period circadian protein homolog 1;
DE Short=mPER1;
DE AltName: Full=Circadian clock protein PERIOD 1;
DE AltName: Full=Circadian pacemaker protein Rigui;
GN Name=Per1; Synonyms=Per, Rigui;
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], AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=9323128; DOI=10.1016/s0092-8674(00)80366-9;
RA Sun Z.S., Albrecht U., Zhuchenko O., Bailey J., Eichele G., Lee C.C.;
RT "Rigui, a putative mammalian ortholog of the Drosophila period gene.";
RL Cell 90:1003-1011(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=9333243; DOI=10.1038/39086;
RA Tei H., Okamura H., Shigeyoshi Y., Fukuhara C., Ozawa R., Hirose M.,
RA Sakaki Y.;
RT "Circadian oscillation of a mammalian homologue of the Drosophila period
RT gene.";
RL Nature 389:512-516(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10857746; DOI=10.1006/geno.2000.6166;
RA Hida A., Koike N., Hirose M., Hattori M., Sakaki Y., Tei H.;
RT "The human and mouse Period1 genes: five well-conserved E-boxes additively
RT contribute to the enhancement of mPer1 transcription.";
RL Genomics 65:224-233(2000).
RN [4]
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 [5]
RP TISSUE SPECIFICITY, AND INDUCTION.
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 [6]
RP FUNCTION, AND 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 [7]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10521578; DOI=10.1016/s0169-328x(99)00192-8;
RA Miyamoto Y., Sancar A.;
RT "Circadian regulation of cryptochrome genes in the mouse.";
RL Brain Res. Mol. Brain Res. 71:238-243(1999).
RN [8]
RP 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 [9]
RP INTERACTION WITH TIMELESS, AND SUBCELLULAR LOCATION.
RX PubMed=10231394; DOI=10.1046/j.1365-2443.1999.00238.x;
RA Takumi T., Nagamine Y., Miyake S., Matsubara C., Taguchi K., Takekida S.,
RA Sakakida Y., Nishikawa K., Kishimoto T., Niwa S., Okumura K., Okamura H.;
RT "A mammalian ortholog of Drosophila timeless, highly expressed in SCN and
RT retina, forms a complex with mPER1.";
RL Genes Cells 4:67-75(1999).
RN [10]
RP INTERACTION WITH PER2, PHOSPHORYLATION BY CKSN1E, NUCLEAR LOCALIZATION
RP SIGNAL, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 831-HIS--ARG-833;
RP 835-LYS--ARG-838 AND 902-THR--THR-914.
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 [11]
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 [12]
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 [13]
RP FUNCTION REPRESSOR OF TRANSLATION, 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 [14]
RP INTERACTION WITH CRY1 AND CRY2, AND SUBCELLULAR LOCATION.
RX PubMed=11875063; DOI=10.1074/jbc.m111466200;
RA Eide E.J., Vielhaber E.L., Hinz W.A., Virshup D.M.;
RT "The circadian regulatory proteins BMAL1 and cryptochromes are substrates
RT of casein kinase Iepsilon.";
RL J. Biol. Chem. 277:17248-17254(2002).
RN [15]
RP PHOSPHORYLATION BY CSNK1D AND CKSN1E, AND UBIQUITINATION.
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 [16]
RP FUNCTION.
RX PubMed=14672706; DOI=10.1016/j.bbrc.2003.11.099;
RA Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R.,
RA Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I.,
RA Kato Y.;
RT "A novel autofeedback loop of Dec1 transcription involved in circadian
RT rhythm regulation.";
RL Biochem. Biophys. Res. Commun. 313:117-124(2004).
RN [17]
RP PHOSPHORYLATION AT SER-661 AND SER-663, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 661-SER--SER-663.
RX PubMed=15148313; DOI=10.1074/jbc.m403433200;
RA Takano A., Isojima Y., Nagai K.;
RT "Identification of mPer1 phosphorylation sites responsible for the nuclear
RT entry.";
RL J. Biol. Chem. 279:32578-32585(2004).
RN [18]
RP INTERACTION WITH PER2; 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 [19]
RP FUNCTION AS PER2 REGULATOR, AND DISRUPTION PHENOTYPE.
RX PubMed=15888647; DOI=10.1523/jneurosci.4761-04.2005;
RA Masubuchi S., Kataoka N., Sassone-Corsi P., Okamura H.;
RT "Mouse Period1 (mPER1) acts as a circadian adaptor to entrain the
RT oscillator to environmental light/dark cycles by regulating mPER2
RT protein.";
RL J. Neurosci. 25:4719-4724(2005).
RN [20]
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 [21]
RP INTERACTION WITH CRY1 AND CRY2, AND SUBCELLULAR LOCATION.
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 [22]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16790549; DOI=10.1073/pnas.0604138103;
RA Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.;
RT "Posttranslational regulation of the mammalian circadian clock by
RT cryptochrome and protein phosphatase 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006).
RN [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
RN [25]
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 [26]
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 [27]
RP INTERACTION WITH USP2, UBIQUITINATION, AND DEUBIQUITINATION.
RX PubMed=23213472; DOI=10.1242/bio.20121990;
RA Yang Y., Duguay D., Bedard N., Rachalski A., Baquiran G., Na C.H.,
RA Fahrenkrug J., Storch K.F., Peng J., Wing S.S., Cermakian N.;
RT "Regulation of behavioral circadian rhythms and clock protein PER1 by the
RT deubiquitinating enzyme USP2.";
RL Biol. Open 1:789-801(2012).
RN [28]
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 [29]
RP FUNCTION CRY2 REPRESSOR, INTERACTION WITH CRY2; CLOCK AND ARNTL, AND TISSUE
RP 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 [30]
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 [31]
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 [32]
RP FUNCTION AS TRANSCRIPTIONAL ACTIVATOR, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24610784; DOI=10.1074/jbc.m113.531095;
RA Richards J., Ko B., All S., Cheng K.Y., Hoover R.S., Gumz M.L.;
RT "A Role for the circadian clock protein Per1 in the regulation of the NaCl
RT Co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse
RT distal convoluted tubule cells.";
RL J. Biol. Chem. 289:11791-11806(2014).
RN [33]
RP FUNCTION IN GR REPRESSION.
RX PubMed=24378737; DOI=10.1016/j.mce.2013.12.013;
RA Han D.H., Lee Y.J., Kim K., Kim C.J., Cho S.;
RT "Modulation of glucocorticoid receptor induction properties by core
RT circadian clock proteins.";
RL Mol. Cell. Endocrinol. 383:170-180(2014).
RN [34]
RP INTERACTION WITH U2AF1L4.
RX PubMed=24837677; DOI=10.1016/j.molcel.2014.04.015;
RA Preussner M., Wilhelmi I., Schultz A.S., Finkernagel F., Michel M.,
RA Moeroey T., Heyd F.;
RT "Rhythmic U2af26 alternative splicing controls PERIOD1 stability and the
RT circadian clock in mice.";
RL Mol. Cell 54:651-662(2014).
RN [35]
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 [36]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 191-502, MUTAGENESIS OF TYR-267;
RP PHE-444 AND TRP-448, FUNCTION IN HEME BINDING, AND SUBUNIT.
RX PubMed=22331899; DOI=10.1073/pnas.1113280109;
RA Kucera N., Schmalen I., Hennig S., Ollinger R., Strauss H.M.,
RA Grudziecki A., Wieczorek C., Kramer A., Wolf E.;
RT "Unwinding the differences of the mammalian PERIOD clock proteins from
RT crystal structure to cellular function.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:3311-3316(2012).
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
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. Regulates circadian target
CC genes expression at post-transcriptional levels, but may not be
CC required for the repression at transcriptional level. Controls PER2
CC protein decay. Represses CRY2 preventing its repression on CLOCK/ARNTL
CC target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver.
CC Besides its involvement in the maintenance of the circadian clock, has
CC an important function in the regulation of several processes.
CC Participates in the repression of glucocorticoid receptor NR3C1/GR-
CC induced transcriptional activity by reducing the association of
CC NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK.
CC Plays a role in the modulation of the neuroinflammatory state via the
CC regulation of inflammatory mediators release, such as CCL2 and IL6. In
CC spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK
CC MAPK cascades as well as the subsequent activation of NFkappaB.
CC Coordinately regulates the expression of multiple genes that are
CC involved in the regulation of renal sodium reabsorption. Can act as
CC gene expression activator in a gene and tissue specific manner, in
CC kidney enhances WNK1 and SLC12A3 expression in collaboration with
CC CLOCK. Modulates hair follicle cycling. Represses the CLOCK-ARNTL/BMAL1
CC induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:11395012,
CC ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:15888647,
CC ECO:0000269|PubMed:21930935, ECO:0000269|PubMed:22331899,
CC ECO:0000269|PubMed:24154698, ECO:0000269|PubMed:24378737,
CC ECO:0000269|PubMed:24610784, ECO:0000269|PubMed:9856465}.
CC -!- SUBUNIT: Homodimer (PubMed:22331899). Component of the circadian core
CC oscillator, which includes the CRY proteins, CLOCK or NPAS2,
CC ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the
CC PER proteins (PubMed:11779462). Interacts directly with TIMELESS
CC (PubMed:10231394, PubMed:9856465). Interacts directly with PER2, PER3,
CC CRY1 and CRY2 (PubMed:10428031, PubMed:10848614, PubMed:11875063,
CC PubMed:14701732, PubMed:16478995, PubMed:24154698). Interacts with
CC ARNTL/BMAL1 and CLOCK (PubMed:16717091, PubMed:24154698). Interacts
CC with GPRASP1 (By similarity). Interacts (phosphorylated) with BTRC and
CC FBXW11; the interactions trigger proteasomal degradation (By
CC similarity). Interacts with NONO and SFPQ (PubMed:22966205). Interacts
CC with WDR5 (By similarity). Interacts with U2AF1L4 (Isoform 3)
CC (PubMed:24837677). Interacts with USP2 (PubMed:23213472). Interacts
CC with HNF4A (By similarity). {ECO:0000250|UniProtKB:O15534,
CC ECO:0000250|UniProtKB:Q8CHI5, ECO:0000269|PubMed:10231394,
CC ECO:0000269|PubMed:10428031, ECO:0000269|PubMed:10848614,
CC ECO:0000269|PubMed:11779462, ECO:0000269|PubMed:11875063,
CC ECO:0000269|PubMed:14701732, ECO:0000269|PubMed:16478995,
CC ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:22331899,
CC ECO:0000269|PubMed:22966205, ECO:0000269|PubMed:23213472,
CC ECO:0000269|PubMed:24154698, ECO:0000269|PubMed:24837677,
CC ECO:0000269|PubMed:9856465}.
CC -!- INTERACTION:
CC O35973; P97784: Cry1; NbExp=3; IntAct=EBI-1266764, EBI-1266607;
CC O35973; Q9R194: Cry2; NbExp=3; IntAct=EBI-1266764, EBI-1266619;
CC O35973; Q9JMK2: Csnk1e; NbExp=2; IntAct=EBI-1266764, EBI-771709;
CC O35973; O54943: Per2; NbExp=5; IntAct=EBI-1266764, EBI-1266779;
CC O35973; Q9R1X4: Timeless; NbExp=3; IntAct=EBI-1266764, EBI-1793117;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nucleocytoplasmic
CC shuttling is effected by interaction with other circadian core
CC oscillator proteins and/or by phosphorylation. Retention of PER1 in the
CC cytoplasm occurs through PER1-PER2 heterodimer formation. Translocate
CC to the nucleus after phosphorylation by CSNK1D or CSNK1E. Also
CC translocated to the nucleus by CRY1 or CRY2.
CC -!- TISSUE SPECIFICITY: In brain, highest expression is observed in the
CC SCN. Highly expressed in the pyramidal cell layer of the piriform
CC cortex, the periventricular part of the caudate-putamen, many thalamic
CC nuclei, and the granular layer of the cerebellar cortex. Weaker
CC expression is detected in most area of the brain, including cortical
CC and non cortical structures. Expression but no oscillations occurs in
CC the glomerular and mitral cell layers of the olfactory bulb, the
CC internal granular layer of the cerebellum, the cornu ammonis and
CC dentate gyrus of the hippocampus, the cerebral and piriform cortices.
CC Expressed in the renal cortex (at protein level). Also found in heart,
CC brain, bladder, lumbar spinal cord, spleen, lung, liver, skeletal
CC muscle and testis. {ECO:0000269|PubMed:10521578,
CC ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:24154698,
CC ECO:0000269|PubMed:24603368, ECO:0000269|PubMed:24610784,
CC ECO:0000269|PubMed:9333243, ECO:0000269|PubMed:9427249}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the suprachiasmatic nucleus (SCN)
CC during late fetal and early neonatal life.
CC -!- INDUCTION: In the suprachiasmatic nucleus (SCN), behaves like a day-
CC type oscillator, with maximum expression during the light period.
CC Oscillations are maintained under constant darkness and are responsive
CC to changes of the light/dark cycles. There is a 4 hour time delay
CC between PER1 and PER2 oscillations. The expression rhythms appear to
CC originate from retina. In liver, peak levels at CT9. In the SCN, levels
CC increase by light exposure during subjective night. Circadian
CC oscillations also observed in skeletal muscle, bladder, lumbar spinal
CC cord and liver but not in testis. {ECO:0000269|PubMed:10521578,
CC ECO:0000269|PubMed:11779462, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:24603368, ECO:0000269|PubMed:9323128,
CC ECO:0000269|PubMed:9333243, ECO:0000269|PubMed:9427249}.
CC -!- PTM: Phosphorylated on serine residues by CSNK1D, CSNK1E and probably
CC also by CSNK1G2. Phosphorylation by CSNK1D or CSNK1E promotes nuclear
CC location of PER proteins as well as ubiquitination and subsequent
CC degradation. May be dephosphorylated by PP1.
CC {ECO:0000269|PubMed:11865049}.
CC -!- PTM: Ubiquitinated; requires phosphorylation by CSNK1E and interaction
CC with BTRC and FBXW11. Deubiquitinated by USP2.
CC {ECO:0000269|PubMed:11865049, ECO:0000269|PubMed:23213472}.
CC -!- DISRUPTION PHENOTYPE: Animals show disrupted circadian behavior. The
CC prolongation of light exposure produces larger phase delay of
CC behavioral rhythm compared to wild-types. Double knocknouts for PER2
CC and PER1 show an abrupt loss of rhythmicity immediately upon transfer
CC to exprosure to constant darkness. Animals have largely affected the
CC water intake (polydipsia) and urine volume (polyuria).
CC {ECO:0000269|PubMed:11395012, ECO:0000269|PubMed:15888647,
CC ECO:0000269|PubMed:24603368}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF022992; AAC53355.1; -; mRNA.
DR EMBL; AB002108; BAA22634.1; -; mRNA.
DR EMBL; AB030818; BAA94086.1; -; Genomic_DNA.
DR EMBL; AL645527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS24882.1; -.
DR PIR; T00019; T00019.
DR RefSeq; NP_001152839.1; NM_001159367.1.
DR RefSeq; NP_035195.2; NM_011065.4.
DR RefSeq; XP_006532543.1; XM_006532480.3.
DR PDB; 4DJ2; X-ray; 2.75 A; A/B/C/D=191-502.
DR PDBsum; 4DJ2; -.
DR AlphaFoldDB; O35973; -.
DR SMR; O35973; -.
DR BioGRID; 202111; 26.
DR ComplexPortal; CPX-3214; Cry2-Per1 complex.
DR ComplexPortal; CPX-3216; Cry1-Per1 complex.
DR DIP; DIP-38519N; -.
DR ELM; O35973; -.
DR IntAct; O35973; 18.
DR MINT; O35973; -.
DR STRING; 10090.ENSMUSP00000021271; -.
DR iPTMnet; O35973; -.
DR PhosphoSitePlus; O35973; -.
DR EPD; O35973; -.
DR MaxQB; O35973; -.
DR PaxDb; O35973; -.
DR PRIDE; O35973; -.
DR ProteomicsDB; 288028; -.
DR Antibodypedia; 24542; 265 antibodies from 35 providers.
DR DNASU; 18626; -.
DR Ensembl; ENSMUST00000021271; ENSMUSP00000021271; ENSMUSG00000020893.
DR Ensembl; ENSMUST00000166748; ENSMUSP00000132635; ENSMUSG00000020893.
DR GeneID; 18626; -.
DR KEGG; mmu:18626; -.
DR UCSC; uc007jpg.2; mouse.
DR CTD; 5187; -.
DR MGI; MGI:1098283; Per1.
DR VEuPathDB; HostDB:ENSMUSG00000020893; -.
DR eggNOG; KOG3753; Eukaryota.
DR GeneTree; ENSGT00940000159217; -.
DR HOGENOM; CLU_006667_0_0_1; -.
DR InParanoid; O35973; -.
DR OMA; GCTGCKC; -.
DR OrthoDB; 145617at2759; -.
DR PhylomeDB; O35973; -.
DR TreeFam; TF318445; -.
DR BioGRID-ORCS; 18626; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Per1; mouse.
DR PRO; PR:O35973; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O35973; protein.
DR Bgee; ENSMUSG00000020893; Expressed in granulocyte and 256 other tissues.
DR ExpressionAtlas; O35973; baseline and differential.
DR Genevisible; O35973; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
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; IEP:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; IMP:UniProtKB.
DR GO; GO:0043967; P:histone H4 acetylation; ISO:MGI.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0042634; P:regulation of hair cycle; ISS:UniProtKB.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0002028; P:regulation of sodium ion transport; IMP:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; IDA:UniProtKB.
DR GO; GO:0009416; P:response to light stimulus; IEP:BHF-UCL.
DR CDD; cd00130; PAS; 1.
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; Biological rhythms; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..1291
FT /note="Period circadian protein homolog 1"
FT /id="PRO_0000162628"
FT DOMAIN 208..275
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 348..414
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 422..465
FT /note="PAC"
FT REGION 1..151
FT /note="Interaction with BTRC"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT REGION 1..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 596..815
FT /note="Required for phosphorylation by CSNK1E"
FT REGION 647..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 749..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 809..873
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 938..1037
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1051..1099
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1148..1291
FT /note="CRY binding domain"
FT REGION 1207..1291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 138..147
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 489..498
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000269|PubMed:11591712"
FT MOTIF 824..840
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:10848614"
FT MOTIF 981..988
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 1042..1046
FT /note="LXXLL"
FT COMPBIAS 19..35
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 647..665
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..769
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 824..845
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 853..873
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 946..968
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 972..989
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1256..1274
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 121
FT /note="Phosphothreonine; by CSNK1E"
FT /evidence="ECO:0000255"
FT MOD_RES 122
FT /note="Phosphoserine; by CSNK1E"
FT /evidence="ECO:0000255"
FT MOD_RES 126
FT /note="Phosphoserine; by CSNK1E"
FT /evidence="ECO:0000255"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15148313"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15148313"
FT MOD_RES 704
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT MOD_RES 979
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT MUTAGEN 267
FT /note="Y->E: No effect on homodimerization. Abolishes
FT homodimerization; when associated with E-444."
FT /evidence="ECO:0000269|PubMed:22331899"
FT MUTAGEN 444
FT /note="F->E: Reduces homodimerization. Abolishes
FT homodimerization; when associated with E-267."
FT /evidence="ECO:0000269|PubMed:22331899"
FT MUTAGEN 448
FT /note="W->E: Abolishes homodimerization."
FT /evidence="ECO:0000269|PubMed:22331899"
FT MUTAGEN 661
FT /note="S->A: Reduced phosphorylation. No nuclear entry of
FT PER1, CRY1 nor CKSN1E; when associated with A-663."
FT MUTAGEN 663
FT /note="S->A: Reduced phosphorylation. No nuclear entry
FT PER1, CRY1 nor CKSN1E; when associated with A-661."
FT MUTAGEN 831..833
FT /note="HCR->ACA: No effect on nuclear import."
FT /evidence="ECO:0000269|PubMed:10848614"
FT MUTAGEN 835..838
FT /note="KAKR->AAKA: Abolishes nuclear accumulation."
FT /evidence="ECO:0000269|PubMed:10848614"
FT MUTAGEN 902..915
FT /note="TSVSPATFPSPLVT->AAVAPAAFPAPLVA: No effect on nuclear
FT import."
FT CONFLICT 1199
FT /note="T -> M (in Ref. 1; AAC53355, 2; BAA22634 and 3;
FT BAA94086)"
FT /evidence="ECO:0000305"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 202..212
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 217..225
FT /evidence="ECO:0007829|PDB:4DJ2"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 237..242
FT /evidence="ECO:0007829|PDB:4DJ2"
FT TURN 247..251
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 254..257
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:4DJ2"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 297..301
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 314..325
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 334..343
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 347..351
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 359..364
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 369..373
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 377..381
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 402..412
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 425..428
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 434..438
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:4DJ2"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:4DJ2"
FT STRAND 451..463
FT /evidence="ECO:0007829|PDB:4DJ2"
FT HELIX 485..498
FT /evidence="ECO:0007829|PDB:4DJ2"
SQ SEQUENCE 1291 AA; 136373 MW; 77FB9BC71EDF31A6 CRC64;
MSGPLEGADG GGDPRPGEPF CPGGVPSPGA PQHRPCPGPS LADDTDANSN GSSGNESNGP
ESRGASQRSS HSSSSGNGKD SALLETTESS KSTNSQSPSP PSSSIAYSLL SASSEQDNPS
TSGCSSEQSA RARTQKELMT ALRELKLRLP PERRGKGRSG TLATLQYALA CVKQVQANQE
YYQQWSLEEG EPCAMDMSTY TLEELEHITS EYTLRNQDTF SVAVSFLTGR IVYISEQAGV
LLRCKRDVFR GARFSELLAP QDVGVFYGST TPSRLPTWGT GTSAGSGLKD FTQEKSVFCR
IRGGPDRDPG PRYQPFRLTP YVTKIRVSDG APAQPCCLLI AERIHSGYEA PRIPPDKRIF
TTRHTPSCLF QDVDERAAPL LGYLPQDLLG APVLLFLHPE DRPLMLAIHK KILQLAGQPF
DHSPIRFCAR NGEYVTMDTS WAGFVHPWSR KVAFVLGRHK VRTAPLNEDV FTPPAPSPAP
SLDSDIQELS EQIHRLLLQP VHSSSPTGLC GVGPLMSPGP LHSPGSSSDS NGGDAEGPGP
PAPVTFQQIC KDVHLVKHQG QQLFIESRAK PPPRPRLLAT GTFKAKVLPC QSPNPELEVA
PVPDQASLAL APEEPERKET SGCSYQQINC LDSILRYLES CNIPSTTKRK CASSSSYTAS
SASDDDKQRA GPVPVGAKKD PSSAMLSGEG ATPRKEPVVG GTLSPLALAN KAESVVSVTS
QCSFSSTIVH VGDKKPPESD IIMMEDLPGL APGPAPSPAP SPTVAPDPTP DAYRPVGLTK
AVLSLHTQKE EQAFLNRFRD LGRLRGLDTS SVAPSAPGCH HGPIPPGRRH HCRSKAKRSR
HHHHQTPRPE TPCYVSHPSP VPSSGPWPPP PATTPFPAMV QPYPLPVFSP RGGPQPLPPA
PTSVSPATFP SPLVTPMVAL VLPNYLFPTP PSYPYGVSQA PVEGPPTPAS HSPSPSLPPP
PLSPPHRPDS PLFNSRCSSP LQLNLLQLEE SPRTEGGAAA GGPGSSAGPL PPSEETAEPE
ARLVEVTESS NQDALSGSSD LLELLLQEDS RSGTGSAASG SLGSGLGSGS GSGSHEGGST
SASITRSSQS SHTSKYFGSI DSSEAEAGAA RARTEPGDQV IKCVLQDPIW LLMANADQRV
MMTYQVPSRD AASVLKQDRE RLRAMQKQQP RFSEDQRREL GAVHSWVRKG QLPRALDVTA
CVDCGSSVQD PGHSDDPLFS ELDGLGLEPM EEGGGEGGGC GVGGGGGDGG EEAQTQIGAK
GSSSQDSAME EEEQGGGSSS PALPAEENST S
