ID PER1_HUMAN Reviewed; 1290 AA. AC O15534; B2RPA8; B4DI49; D3DTR3; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 16-DEC-2008, sequence version 2. DT 24-JAN-2024, entry version 210. DE RecName: Full=Period circadian protein homolog 1; DE Short=hPER1; DE AltName: Full=Circadian clock protein PERIOD 1; DE AltName: Full=Circadian pacemaker protein Rigui; GN Name=PER1; Synonyms=KIAA0482, PER, RIGUI; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND VARIANT PRO-962. RC TISSUE=Heart; 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 VARIANT PRO-962. RC 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], AND VARIANT PRO-962. RX PubMed=10940553; DOI=10.1016/s0378-1119(00)00248-1; RA Taruscio D., Zoraqi G.K., Falchi M., Iosi F., Paradisi S., Di Fiore B., RA Lavia P., Falbo V.; RT "The human Per1 gene: genomic organization and promoter analysis of the RT first human orthologue of the Drosophila period gene."; RL Gene 253:161-170(2000). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-962. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-962. RC TISSUE=Brain; RX PubMed=9455484; DOI=10.1093/dnares/4.5.345; RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., RA Nomura N., Ohara O.; RT "Characterization of cDNA clones in size-fractionated cDNA libraries from RT human brain."; RL DNA Res. 4:345-349(1997). RN [6] RP SEQUENCE REVISION. RA Nagase T., Kikuno R., Ohara O.; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Corpus callosum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-962. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-962. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP TISSUE SPECIFICITY. 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 [12] RP PHOSPHORYLATION BY CSNK1E. RX PubMed=10790862; DOI=10.1097/00001756-200004070-00011; RA Keesler G.A., Camacho F., Guo Y., Virshup D., Mondadori C., Yao Z.; RT "Phosphorylation and destabilization of human period I clock protein by RT human casein kinase I epsilon."; RL NeuroReport 11:951-955(2000). RN [13] RP PHOSPHORYLATION BY CSNK1D. RX PubMed=11165242; DOI=10.1016/s0014-5793(00)02434-0; RA Camacho F., Cilio M., Guo Y., Virshup D.M., Patel K., Khorkova O., RA Styren S., Morse B., Yao Z., Keesler G.A.; RT "Human casein kinase Idelta phosphorylation of human circadian clock RT proteins period 1 and 2."; RL FEBS Lett. 489:159-165(2001). RN [14] RP PHOSPHORYLATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=14750904; DOI=10.1042/bj20031308; RA Miyazaki K., Nagase T., Mesaki M., Narukawa J., Ohara O., Ishida N.; RT "Phosphorylation of clock protein PER1 regulates its circadian degradation RT in normal human fibroblasts."; RL Biochem. J. 380:95-103(2004). RN [15] RP INTERACTION WITH BTRC AND FBXW11, PHOSPHORYLATION AT THR-121; SER-122 AND RP SER-126, UBIQUITINATION, AND MUTAGENESIS OF 210-SER--THR-213; RP 714-SER--SER-726 AND 794-PHE--PHE-798. RX PubMed=15917222; DOI=10.1074/jbc.m502862200; RA Shirogane T., Jin J., Ang X.L., Harper J.W.; RT "SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1- RT dependent degradation of the mammalian period-1 (Per1) protein."; RL J. Biol. Chem. 280:26863-26872(2005). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-979 AND SER-980, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704 AND SER-815, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-815, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704 AND SER-815, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] 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 [24] RP FUNCTION IN HAIR GROWTH, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=24005054; DOI=10.1038/jid.2013.366; RA Al-Nuaimi Y., Hardman J.A., Biro T., Haslam I.S., Philpott M.P., Toth B.I., RA Farjo N., Farjo B., Baier G., Watson R.E., Grimaldi B., Kloepper J.E., RA Paus R.; RT "A meeting of two chronobiological systems: circadian proteins Period1 and RT BMAL1 modulate the human hair cycle clock."; RL J. Invest. Dermatol. 134:610-619(2014). RN [25] 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 [26] RP INTERACTION WITH HNF4A. RX PubMed=30530698; DOI=10.1073/pnas.1816411115; RA Qu M., Duffy T., Hirota T., Kay S.A.; RT "Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue- RT specific circadian networks."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E12305-E12312(2018). RN [27] RP VARIANTS [LARGE SCALE ANALYSIS] GLN-696; SER-985 AND LEU-1060. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [28] RP VARIANT GLN-422. RX PubMed=27717682; DOI=10.1016/j.jstrokecerebrovasdis.2016.09.003; RA Mukawa M., Nariai T., Onda H., Yoneyama T., Aihara Y., Hirota K., Kudo T., RA Sumita K., Maehara T., Kawamata T., Kasuya H., Akagawa H.; RT "Exome sequencing identified CCER2 as a novel candidate gene for Moyamoya RT disease."; RL J. Stroke Cerebrovasc. Dis. 26:150-161(2017). 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:24005054}. CC -!- SUBUNIT: Homodimer (By similarity). 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 (By CC similarity). Interacts directly with TIMELESS, PER2, PER3, CRY1 and CC CRY2 (By similarity). Interacts with BMAL1 and CLOCK (By similarity). CC Interacts with GPRASP1 (By similarity). Interacts (phosphorylated) with CC BTRC and FBXW11; the interactions trigger proteasomal degradation CC (PubMed:15917222). Interacts with NONO, WDR5 and SFPQ (By similarity). CC Interacts with USP2 (By similarity). Interacts with HNF4A CC (PubMed:30530698). {ECO:0000250|UniProtKB:O35973, CC ECO:0000250|UniProtKB:Q8CHI5, ECO:0000269|PubMed:15917222, CC ECO:0000269|PubMed:30530698}. CC -!- INTERACTION: CC O15534; Q92870-2: APBB2; NbExp=3; IntAct=EBI-2557276, EBI-21535880; CC O15534; P46379-2: BAG6; NbExp=3; IntAct=EBI-2557276, EBI-10988864; CC O15534; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-2557276, EBI-2837444; CC O15534; P55212: CASP6; NbExp=3; IntAct=EBI-2557276, EBI-718729; CC O15534; Q99832: CCT7; NbExp=3; IntAct=EBI-2557276, EBI-357046; CC O15534; P29692-2: EEF1D; NbExp=3; IntAct=EBI-2557276, EBI-5280572; CC O15534; P41091: EIF2S3; NbExp=3; IntAct=EBI-2557276, EBI-1054228; CC O15534; O75460-2: ERN1; NbExp=3; IntAct=EBI-2557276, EBI-25852368; CC O15534; P22607: FGFR3; NbExp=3; IntAct=EBI-2557276, EBI-348399; CC O15534; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-2557276, EBI-10226858; CC O15534; P14136: GFAP; NbExp=3; IntAct=EBI-2557276, EBI-744302; CC O15534; Q14957: GRIN2C; NbExp=3; IntAct=EBI-2557276, EBI-8285963; CC O15534; P28799: GRN; NbExp=3; IntAct=EBI-2557276, EBI-747754; CC O15534; P06396: GSN; NbExp=3; IntAct=EBI-2557276, EBI-351506; CC O15534; P01112: HRAS; NbExp=3; IntAct=EBI-2557276, EBI-350145; CC O15534; P54652: HSPA2; NbExp=3; IntAct=EBI-2557276, EBI-356991; CC O15534; P04792: HSPB1; NbExp=3; IntAct=EBI-2557276, EBI-352682; CC O15534; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2557276, EBI-1055254; CC O15534; O60333-2: KIF1B; NbExp=3; IntAct=EBI-2557276, EBI-10975473; CC O15534; O14901: KLF11; NbExp=3; IntAct=EBI-2557276, EBI-948266; CC O15534; O60356: NUPR1; NbExp=3; IntAct=EBI-2557276, EBI-3908808; CC O15534; P07237: P4HB; NbExp=3; IntAct=EBI-2557276, EBI-395883; CC O15534; P60201-2: PLP1; NbExp=3; IntAct=EBI-2557276, EBI-12188331; CC O15534; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-2557276, EBI-5280197; CC O15534; P60891: PRPS1; NbExp=3; IntAct=EBI-2557276, EBI-749195; CC O15534; P62826: RAN; NbExp=3; IntAct=EBI-2557276, EBI-286642; CC O15534; P49591: SARS1; NbExp=3; IntAct=EBI-2557276, EBI-1053431; CC O15534; Q9P1I4: ST13; NbExp=3; IntAct=EBI-2557276, EBI-25892254; CC O15534; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-2557276, EBI-741480; CC O15534; O76024: WFS1; NbExp=3; IntAct=EBI-2557276, EBI-720609; CC O15534; Q9R194: Cry2; Xeno; NbExp=3; IntAct=EBI-2557276, EBI-1266619; 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 (By similarity). CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=Rigui 4.7; CC IsoId=O15534-1; Sequence=Displayed; CC Name=Rigui 3.0; CC IsoId=O15534-2; Sequence=Not described; CC Name=Rigui 6.6; Synonyms=Truncated; CC IsoId=O15534-3; Sequence=Not described; CC Name=2; CC IsoId=O15534-4; Sequence=VSP_056205, VSP_056206, VSP_056207; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in hair follicles (at CC protein level).Found in heart, brain, placenta, lung, liver, skeletal CC muscle, pancreas, kidney, spleen, thymus, prostate, testis, ovary and CC small intestine. Highest level in skeletal muscle. CC {ECO:0000269|PubMed:14750904, ECO:0000269|PubMed:24005054, CC ECO:0000269|PubMed:9333243, ECO:0000269|PubMed:9427249}. CC -!- INDUCTION: Serum-induced levels in fibroblasts show circadian CC oscillations. Maximum levels after 1 hour stimulation, minimum levels CC after 12 hours. Another peak is then observed after 20 hours. Protein CC levels show maximum levels at 6 hours, decrease to reach minimum levels CC at 20 hours, and increase again to reach a second peak after 26 hours. CC Levels then decrease slightly and then increase to maximum levels at 32 CC hours. Levels of phosphorylated form increase between 3 hours and 12 CC hours. {ECO:0000269|PubMed:14750904}. 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:15917222}. CC -!- PTM: Ubiquitinated; requires phosphorylation by CSNK1E and interaction CC with BTRC and FBXW11. Deubiquitinated by USP2 (By similarity). CC {ECO:0000250|UniProtKB:O35973, ECO:0000269|PubMed:15917222}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC06326.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AF022991; AAC51765.1; -; mRNA. DR EMBL; AB002107; BAA22633.1; -; mRNA. DR EMBL; AF102137; AAF15544.1; -; Genomic_DNA. DR EMBL; AB030817; BAA94085.1; -; Genomic_DNA. DR EMBL; AB088477; BAC06326.2; ALT_INIT; mRNA. DR EMBL; AK295410; BAG58361.1; -; mRNA. DR EMBL; AC129492; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90090.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90091.1; -; Genomic_DNA. DR EMBL; BC137346; AAI37347.1; -; mRNA. DR CCDS; CCDS11131.1; -. [O15534-1] DR PIR; T00018; T00018. DR RefSeq; NP_002607.2; NM_002616.2. [O15534-1] DR RefSeq; XP_005256746.1; XM_005256689.1. DR AlphaFoldDB; O15534; -. DR SMR; O15534; -. DR BioGRID; 111210; 110. DR ComplexPortal; CPX-3221; Cry2-Per1 complex. DR ComplexPortal; CPX-3222; Cry1-Per1 complex. DR DIP; DIP-56603N; -. DR IntAct; O15534; 59. DR MINT; O15534; -. DR STRING; 9606.ENSP00000314420; -. DR GlyGen; O15534; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O15534; -. DR PhosphoSitePlus; O15534; -. DR BioMuta; PER1; -. DR EPD; O15534; -. DR jPOST; O15534; -. DR MassIVE; O15534; -. DR MaxQB; O15534; -. DR PaxDb; 9606-ENSP00000314420; -. DR PeptideAtlas; O15534; -. DR ProteomicsDB; 4276; -. DR ProteomicsDB; 48743; -. [O15534-1] DR Pumba; O15534; -. DR Antibodypedia; 24542; 282 antibodies from 35 providers. DR DNASU; 5187; -. DR Ensembl; ENST00000317276.9; ENSP00000314420.4; ENSG00000179094.16. [O15534-1] DR Ensembl; ENST00000354903.9; ENSP00000346979.5; ENSG00000179094.16. [O15534-4] DR GeneID; 5187; -. DR KEGG; hsa:5187; -. DR MANE-Select; ENST00000317276.9; ENSP00000314420.4; NM_002616.3; NP_002607.2. DR UCSC; uc002gkd.4; human. [O15534-1] DR AGR; HGNC:8845; -. DR CTD; 5187; -. DR DisGeNET; 5187; -. DR GeneCards; PER1; -. DR HGNC; HGNC:8845; PER1. DR HPA; ENSG00000179094; Low tissue specificity. DR MIM; 602260; gene. DR neXtProt; NX_O15534; -. DR OpenTargets; ENSG00000179094; -. DR PharmGKB; PA33184; -. DR VEuPathDB; HostDB:ENSG00000179094; -. DR eggNOG; KOG3753; Eukaryota. DR GeneTree; ENSGT00940000159217; -. DR HOGENOM; CLU_006667_0_0_1; -. DR InParanoid; O15534; -. DR OMA; GCTGCKC; -. DR OrthoDB; 2971905at2759; -. DR PhylomeDB; O15534; -. DR TreeFam; TF318445; -. DR PathwayCommons; O15534; -. DR Reactome; R-HSA-400253; Circadian Clock. DR SignaLink; O15534; -. DR SIGNOR; O15534; -. DR BioGRID-ORCS; 5187; 13 hits in 1161 CRISPR screens. DR ChiTaRS; PER1; human. DR GeneWiki; PER1; -. DR GenomeRNAi; 5187; -. DR Pharos; O15534; Tbio. DR PRO; PR:O15534; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O15534; Protein. DR Bgee; ENSG00000179094; Expressed in mucosa of stomach and 206 other cell types or tissues. DR ExpressionAtlas; O15534; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl. DR GO; GO:0070888; F:E-box binding; IDA:BHF-UCL. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central. DR GO; GO:0001222; F:transcription corepressor binding; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB. DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:UniProtKB. DR GO; GO:0097167; P:circadian regulation of translation; ISS:UniProtKB. DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB. DR GO; GO:0009649; P:entrainment of circadian clock; TAS:ProtInc. DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS: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; ISS:UniProtKB. DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; 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; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS: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; IMP:UniProtKB. DR GO; GO:1900744; P:regulation of p38MAPK cascade; ISS:UniProtKB. DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. 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; O15534; HS. PE 1: Evidence at protein level; KW Alternative splicing; Biological rhythms; Cytoplasm; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..1290 FT /note="Period circadian protein homolog 1" FT /id="PRO_0000162627" 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:0000269|PubMed:15917222" 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 /evidence="ECO:0000250" FT REGION 646..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 805..874 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 938..977 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 996..1037 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1051..1098 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1149..1290 FT /note="CRY binding domain" FT /evidence="ECO:0000250" FT REGION 1207..1290 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:0000250|UniProtKB:O35973" FT MOTIF 827..843 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:O35973" FT MOTIF 982..989 FT /note="Nuclear export signal 3" FT /evidence="ECO:0000250|UniProtKB:O54943" FT MOTIF 1043..1047 FT /note="LXXLL" FT COMPBIAS 21..37 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 646..670 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 827..845 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 857..874 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 947..970 FT /note="Pro 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:0000250|UniProtKB:O35973" FT MOD_RES 663 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35973" FT MOD_RES 704 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 815 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 979 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 980 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT VAR_SEQ 1..32 FT /note="MSGPLEGADGGGDPRPGESFCPGGVPSPGPPQ -> MLEVLEEIWSVRARRA FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056205" FT VAR_SEQ 822..875 FT /note="CHHGPAPPSRRHHCRSKAKRSRHHQNPRAEAPCYVSHPSPVPPSTPWPTPPA FT TT -> SHLGPPGACPLPSLGLDCWGVGLKGGVSAPGTQAGVASTTRPCLGTGPSLASP FT H (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056206" FT VAR_SEQ 876..1290 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056207" FT VARIANT 422 FT /note="H -> Q (found in a patient with Moyamoya disease; FT uncertain significance; dbSNP:rs1464745710)" FT /evidence="ECO:0000269|PubMed:27717682" FT /id="VAR_079176" FT VARIANT 696 FT /note="E -> Q (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036038" FT VARIANT 962 FT /note="A -> P (in dbSNP:rs2585405)" FT /evidence="ECO:0000269|PubMed:10857746, FT ECO:0000269|PubMed:10940553, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9323128, ECO:0000269|PubMed:9333243, FT ECO:0000269|PubMed:9455484, ECO:0000269|Ref.9" FT /id="VAR_047899" FT VARIANT 968 FT /note="R -> H (in dbSNP:rs3027193)" FT /id="VAR_047900" FT VARIANT 985 FT /note="N -> S (in a breast cancer sample; somatic mutation; FT dbSNP:rs1323588262)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036039" FT VARIANT 1060 FT /note="S -> L (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs761958964)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036040" FT MUTAGEN 121..126 FT /note="TSGCSS->AAGCSA: Strongly decreases interaction with FT BTRC and FBXW11 and inhibits degradation promoted by FT CSNK1E." FT MUTAGEN 210..213 FT /note="SEYT->AEYA: No effect on interaction with BTRC and FT FBXW11." FT /evidence="ECO:0000269|PubMed:15917222" FT MUTAGEN 714..726 FT /note="SVVSVTSQCSFSS->AVVAVTAQCAFAA: No effect on FT interaction with BTRC and FBXW11." FT /evidence="ECO:0000269|PubMed:15917222" FT MUTAGEN 794..798 FT /note="FLSRF->ALSRA: Strongly decreases interaction with FT BTRC and FBXW11." FT /evidence="ECO:0000269|PubMed:15917222" SQ SEQUENCE 1290 AA; 136212 MW; 60B844468EEF4D1B CRC64; MSGPLEGADG GGDPRPGESF CPGGVPSPGP PQHRPCPGPS LADDTDANSN GSSGNESNGH ESRGASQRSS HSSSSGNGKD SALLETTESS KSTNSQSPSP PSSSIAYSLL SASSEQDNPS TSGCSSEQSA RARTQKELMT ALRELKLRLP PERRGKGRSG TLATLQYALA CVKQVQANQE YYQQWSLEEG EPCSMDMSTY TLEELEHITS EYTLQNQDTF SVAVSFLTGR IVYISEQAAV LLRCKRDVFR GTRFSELLAP QDVGVFYGST APSRLPTWGT GASAGSGLRD FTQEKSVFCR IRGGPDRDPG PRYQPFRLTP YVTKIRVSDG APAQPCCLLI AERIHSGYEA PRIPPDKRIF TTRHTPSCLF QDVDERAAPL LGYLPQDLLG APVLLFLHPE DRPLMLAIHK KILQLAGQPF DHSPIRFCAR NGEYVTMDTS WAGFVHPWSR KVAFVLGRHK VRTAPLNEDV FTPPAPSPAP SLDTDIQELS EQIHRLLLQP VHSPSPTGLC GVGAVTSPGP LHSPGSSSDS NGGDAEGPGP PAPVTFQQIC KDVHLVKHQG QQLFIESRAR PQSRPRLPAT GTFKAKALPC QSPDPELEAG SAPVQAPLAL VPEEAERKEA SSCSYQQINC LDSILRYLES CNLPSTTKRK CASSSSYTTS SASDDDRQRT GPVSVGTKKD PPSAALSGEG ATPRKEPVVG GTLSPLALAN KAESVVSVTS QCSFSSTIVH VGDKKPPESD IIMMEDLPGL APGPAPSPAP SPTVAPDPAP DAYRPVGLTK AVLSLHTQKE EQAFLSRFRD LGRLRGLDSS STAPSALGER GCHHGPAPPS RRHHCRSKAK RSRHHQNPRA EAPCYVSHPS PVPPSTPWPT PPATTPFPAV VQPYPLPVFS PRGGPQPLPP APTSVPPAAF PAPLVTPMVA LVLPNYLFPT PSSYPYGALQ TPAEGPPTPA SHSPSPSLPA LAPSPPHRPD SPLFNSRCSS PLQLNLLQLE ELPRAEGAAV AGGPGSSAGP PPPSAEAAEP EARLAEVTES SNQDALSGSS DLLELLLQED SRSGTGSAAS GSLGSGLGSG SGSGSHEGGS TSASITRSSQ SSHTSKYFGS IDSSEAEAGA ARGGAEPGDQ VIKYVLQDPI WLLMANADQR VMMTYQVPSR DMTSVLKQDR ERLRAMQKQQ PRFSEDQRRE LGAVHSWVRK GQLPRALDVM ACVDCGSSTQ DPGHPDDPLF SELDGLGLEP MEEGGGEQGS SGGGSGEGEG CEEAQGGAKA SSSQDLAMEE EEEGRSSSSP ALPTAGNCTS //