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 24-JAN-2024, entry version 185. 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 BMAL1. 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 BMAL1, 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, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a CC critical role in rhythm generation, whereas delays imposed by post- CC translational modifications (PTMs) are important for determining the CC period (tau) of the rhythms (tau refers to the period of a rhythm and CC is the length, in time, of one complete cycle). A diurnal rhythm is CC synchronized with the day/night cycle, while the ultradian and CC infradian rhythms have a period shorter and longer than 24 hours, CC respectively. Disruptions in the circadian rhythms contribute to the CC pathology of cardiovascular diseases, cancer, metabolic syndromes and CC aging. A transcription/translation feedback loop (TTFL) forms the core CC of the molecular circadian clock mechanism. Transcription factors, CC CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the CC 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-BMAL1|BMAL2 heterodimer CC inhibiting its activity and thereby negatively regulating their own CC expression. This heterodimer also activates nuclear receptors NR1D1/2 CC and RORA/B/G, which form a second feedback loop and which activate and CC repress 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/BMAL1 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 BMAL1: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-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, BMAL1 or CC BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins CC (PubMed:11779462). Interacts directly with TIMELESS (PubMed:10231394, CC PubMed:9856465). Interacts directly with PER2, PER3, CRY1 and CRY2 CC (PubMed:10428031, PubMed:10848614, PubMed:11875063, PubMed:14701732, CC PubMed:16478995, PubMed:24154698). Interacts with BMAL1 and CLOCK CC (PubMed:16717091, PubMed:24154698). Interacts with GPRASP1 (By CC similarity). Interacts (phosphorylated) with BTRC and FBXW11; the CC interactions trigger proteasomal degradation (By similarity). Interacts CC with NONO and SFPQ (PubMed:22966205). Interacts with WDR5 (By CC similarity). Interacts with U2AF1L4 (Isoform 3) (PubMed:24837677). CC Interacts with USP2 (PubMed:23213472). Interacts with HNF4A (By CC 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; 27. 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 GlyGen; O35973; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O35973; -. DR PhosphoSitePlus; O35973; -. DR EPD; O35973; -. DR MaxQB; O35973; -. DR PaxDb; 10090-ENSMUSP00000021271; -. DR ProteomicsDB; 288028; -. DR Pumba; O35973; -. DR Antibodypedia; 24542; 282 antibodies from 35 providers. DR DNASU; 18626; -. DR Ensembl; ENSMUST00000021271.14; ENSMUSP00000021271.8; ENSMUSG00000020893.18. DR Ensembl; ENSMUST00000166748.8; ENSMUSP00000132635.2; ENSMUSG00000020893.18. DR GeneID; 18626; -. DR KEGG; mmu:18626; -. DR UCSC; uc007jpg.2; mouse. DR AGR; MGI:1098283; -. 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; 2971905at2759; -. DR PhylomeDB; O35973; -. DR TreeFam; TF318445; -. DR BioGRID-ORCS; 18626; 2 hits in 81 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 259 other cell types or tissues. DR ExpressionAtlas; O35973; baseline and differential. 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:0006338; P:chromatin remodeling; IMP: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; IEP:UniProtKB. DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB. DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; IMP: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: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 CDD; cd00130; PAS; 1. DR Gene3D; 3.30.450.20; PAS domain; 2. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013655; PAS_fold_3. DR InterPro; IPR048814; Per1-3_PAS-A. DR InterPro; IPR022728; Period_circadian-like_C. DR PANTHER; PTHR11269; PERIOD CIRCADIAN PROTEIN; 1. DR PANTHER; PTHR11269:SF8; PERIOD CIRCADIAN PROTEIN HOMOLOG 1; 1. DR Pfam; PF08447; PAS_3; 1. DR Pfam; PF21353; Per3-like_PAS-A; 1. DR Pfam; PF12114; Period_C; 1. DR SMART; SM00091; PAS; 2. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 1. DR PROSITE; PS50112; PAS; 1. DR Genevisible; O35973; MM. 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 //