PER1_HUMAN
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 03-AUG-2022, entry version 202.
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, 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:24005054}.
CC -!- SUBUNIT: Homodimer (By similarity). 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 (By similarity). Interacts directly with TIMELESS, PER2,
CC PER3, CRY1 and CRY2 (By similarity). Interacts with ARNTL/BMAL1 and
CC CLOCK (By similarity). Interacts with GPRASP1 (By similarity).
CC Interacts (phosphorylated) with BTRC and FBXW11; the interactions
CC trigger proteasomal degradation (PubMed:15917222). Interacts with NONO,
CC WDR5 and SFPQ (By similarity). Interacts with USP2 (By similarity).
CC Interacts with HNF4A (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};
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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. [O15534-1]
DR AlphaFoldDB; O15534; -.
DR SMR; O15534; -.
DR BioGRID; 111210; 109.
DR ComplexPortal; CPX-3221; Cry2-Per1 complex.
DR ComplexPortal; CPX-3222; Cry1-Per1 complex.
DR DIP; DIP-56603N; -.
DR IntAct; O15534; 60.
DR MINT; O15534; -.
DR STRING; 9606.ENSP00000314420; -.
DR iPTMnet; O15534; -.
DR PhosphoSitePlus; O15534; -.
DR BioMuta; PER1; -.
DR EPD; O15534; -.
DR jPOST; O15534; -.
DR MassIVE; O15534; -.
DR MaxQB; O15534; -.
DR PaxDb; O15534; -.
DR PeptideAtlas; O15534; -.
DR PRIDE; O15534; -.
DR ProteomicsDB; 4276; -.
DR ProteomicsDB; 48743; -. [O15534-1]
DR Antibodypedia; 24542; 265 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 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; 145617at2759; -.
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; 12 hits in 1083 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 204 other tissues.
DR ExpressionAtlas; O15534; baseline and differential.
DR Genevisible; O15534; HS.
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: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:0043966; P:histone H3 acetylation; IDA:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB.
DR GO; GO:0043967; P:histone H4 acetylation; IDA:UniProtKB.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISS: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; ISS:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
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 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 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 unknown pathological 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
