PER2_HUMAN
ID PER2_HUMAN Reviewed; 1255 AA.
AC O15055; A2I2P7; Q4ZG49; Q6DT41; Q9UQ45;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Period circadian protein homolog 2;
DE Short=hPER2;
DE AltName: Full=Circadian clock protein PERIOD 2;
GN Name=PER2; Synonyms=KIAA0347;
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] (ISOFORM 2).
RC TISSUE=Brain;
RA Ikeda M., Takehara N., Ebisawa T., Yamauchi T., Nomura M.;
RT "cDNA cloning and characterization of Per2S, an alternatively spliced human
RT Per2 variant.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, AND INTERACTION
RP WITH CSNK1D.
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [5]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Nagase T., Ishikawa K., Seki N., Nakajima D., Ohira M., Miyajima N.,
RA Kotani H., Nomura N., Ohara O.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65.
RA Carpen J.D., Archer S.N., Skene D.J., Smits M., von Schantz M.;
RT "A single-nucleotide polymorphism in the 5'-untranslated region of the
RT hPER2 gene is associated with diurnal preference.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
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 [10]
RP 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 [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=22274616; DOI=10.1038/emboj.2012.1;
RA Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A.,
RA Zhao Z., Lee C.C., Chang K.S.;
RT "PML regulates PER2 nuclear localization and circadian function.";
RL EMBO J. 31:1427-1439(2012).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), AND
RP TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=24202686; DOI=10.1007/s00018-013-1503-1;
RA Avitabile D., Genovese L., Ponti D., Ranieri D., Raffa S., Calogero A.,
RA Torrisi M.R.;
RT "Nucleolar localization and circadian regulation of Per2S, a novel splicing
RT variant of the Period 2 gene.";
RL Cell. Mol. Life Sci. 71:2547-2559(2014).
RN [13]
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 [14]
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 [15]
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 [16]
RP VARIANT FASPS1 GLY-662, PHOSPHORYLATION AT SER-662, AND MUTAGENESIS OF
RP SER-662.
RX PubMed=11232563; DOI=10.1126/science.1057499;
RA Toh K.L., Jones C.R., He Y., Eide E.J., Hinz W.A., Virshup D.M.,
RA Ptacek L.J., Fu Y.-H.;
RT "An hPer2 phosphorylation site mutation in familial advanced sleep phase
RT syndrome.";
RL Science 291:1040-1043(2001).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-823.
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).
CC -!- FUNCTION: Transcriptional repressor which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic syndrome
CC and aging. A transcription/translation feedback loop (TTFL) forms the
CC core of the molecular circadian clock mechanism. Transcription factors,
CC CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb
CC of the feedback loop, act in the form of a heterodimer and activate the
CC transcription of core clock genes and clock-controlled genes (involved
CC in key metabolic processes), harboring E-box elements (5'-CACGTG-3')
CC within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which
CC are transcriptional repressors form the negative limb of the feedback
CC loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2
CC heterodimer inhibiting its activity and thereby negatively regulating
CC their own expression. This heterodimer also activates nuclear receptors
CC NR1D1/2 and RORA/B/G, which form a second feedback loop and which
CC activate and repress ARNTL/BMAL1 transcription, respectively. PER1 and
CC PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate
CC circadian timing, but also contribute directly to repression of clock-
CC controlled target genes through interaction with several classes of
CC RNA-binding proteins, helicases and others transcriptional repressors.
CC PER appears to regulate circadian control of transcription by at least
CC three different modes. First, interacts directly with the CLOCK-
CC ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit
CC complexes containing the SIN3-HDAC that remodel chromatin to repress
CC transcription. Second, brings H3K9 methyltransferases such as SUV39H1
CC and SUV39H2 to the E-box elements of the circadian target genes, like
CC PER2 itself or PER1. The recruitment of each repressive modifier to the
CC DNA seems to be very precisely temporally orchestrated by the large PER
CC complex, the deacetylases acting before than the methyltransferases.
CC Additionally, large PER complexes are also recruited to the target
CC genes 3' termination site through interactions with RNA-binding
CC proteins and helicases that may play a role in transcription
CC termination to regulate transcription independently of CLOCK-
CC ARTNL/BMAL1 interactions. Recruitment of large PER complexes to the
CC elongating polymerase at PER and CRY termination sites inhibited SETX
CC action, impeding RNA polymerase II release and thereby repressing
CC transcriptional reinitiation. May propagate clock information to
CC metabolic pathways via the interaction with nuclear receptors.
CC Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at
CC the promoter of nuclear receptors target genes like ARNTL or G6PC1.
CC Directly and specifically represses PPARG proadipogenic activity by
CC blocking PPARG recruitment to target promoters and thereby inhibiting
CC transcriptional activation. Required for fatty acid and lipid
CC metabolism, is involved as well in the regulation of circulating
CC insulin levels. Plays an important role in the maintenance of
CC cardiovascular functions through the regulation of NO and
CC vasodilatatory prostaglandins production in aortas. Controls circadian
CC glutamate uptake in synaptic vesicles through the regulation of VGLUT1
CC expression. May also be involved in the regulation of inflammatory
CC processes. Represses the CLOCK-ARNTL/BMAL1 induced transcription of
CC BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the
CC TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1.
CC {ECO:0000250|UniProtKB:O54943}.
CC -!- SUBUNIT: Homodimer. Component of the circadian core oscillator, which
CC includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2,
CC CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts with
CC CLOCK-ARNTL/BMAL1 (off DNA).Interacts with ARNTL2/BMAL2. Interacts
CC directly with PER1 and PER3, and through a C-terminal domain, with CRY1
CC and CRY2. Interacts, via its second PAS domain, with TIMELESS in vitro.
CC Interacts with NFIL3. Different large complexes have been identified
CC with different repressive functions. The core of PER complexes is
CC composed of at least PER1, PER2, PER3, CRY1, CRY2, CSNK1D and/or
CC CSNK1E. The large PER complex involved in the repression of
CC transcriptional termination is composed of at least PER2, CDK9, DDX5,
CC DHX9, NCBP1 and POLR2A (active). The large PER complex involved in the
CC histone deacetylation is composed of at least HDAC1, PER2, SFPQ and
CC SIN3A. The large PER complex involved in the histone methylation is
CC composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3
CC mediates the formation of the complex. Interacts with SETX; the
CC interaction inhibits termination of circadian target genes. Interacts
CC with the nuclear receptors HNF4A, NR1D1, NR4A2, RORA, PPARA, PPARG and
CC THRA; the interaction with at least PPARG is ligand dependent.
CC Interacts with PML. Interacts (phosphorylated) with BTRC and FBXW11;
CC the interactions trigger proteasomal degradation. Interacts with NONO
CC and SFPQ. Interacts with CAVIN3 (By similarity). Interacts with MAGEL2
CC (By similarity). Interacts with MAP1LC3B (By similarity). Interacts
CC with HNF4A (PubMed:30530698). {ECO:0000250|UniProtKB:O54943,
CC ECO:0000269|PubMed:11165242, ECO:0000269|PubMed:22274616,
CC ECO:0000269|PubMed:30530698}.
CC -!- INTERACTION:
CC O15055; P48730: CSNK1D; NbExp=4; IntAct=EBI-1054296, EBI-751621;
CC O15055; P49674: CSNK1E; NbExp=6; IntAct=EBI-1054296, EBI-749343;
CC O15055; Q14241: ELOA; NbExp=3; IntAct=EBI-1054296, EBI-742350;
CC O15055; Q96PV6: LENG8; NbExp=3; IntAct=EBI-1054296, EBI-739546;
CC O15055; P61968: LMO4; NbExp=3; IntAct=EBI-1054296, EBI-2798728;
CC O15055; P40692: MLH1; NbExp=3; IntAct=EBI-1054296, EBI-744248;
CC O15055; J3QSH9: PER1; NbExp=3; IntAct=EBI-1054296, EBI-10178671;
CC O15055; P29590: PML; NbExp=3; IntAct=EBI-1054296, EBI-295890;
CC O15055; P11441: UBL4A; NbExp=3; IntAct=EBI-1054296, EBI-356983;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:22274616}. Cytoplasm
CC {ECO:0000250|UniProtKB:O54943}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:O54943}. Note=Nucleocytoplasmic shuttling is
CC effected by interaction with other circadian core oscillator proteins
CC and/or by phosphorylation. Translocate to the nucleus after
CC phosphorylation by CSNK1D or CSNK1E. Also translocated to the nucleus
CC by CRY1 or CRY2. PML regulates its nuclear localization.
CC {ECO:0000250|UniProtKB:O54943}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, nucleolus
CC {ECO:0000269|PubMed:24202686}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15055-1; Sequence=Displayed;
CC Name=2; Synonyms=PER2S;
CC IsoId=O15055-2; Sequence=VSP_021653, VSP_021654;
CC -!- TISSUE SPECIFICITY: Widely expressed. Found in heart, brain, placenta,
CC lung, liver, skeleatal muscle, kidney and pancreas. High levels in
CC skeletal muscle and pancreas. Low levels in lung. Isoform 2 is
CC expressed in keratinocytes (at protein level).
CC {ECO:0000269|PubMed:9427249}.
CC -!- INDUCTION: Oscillates diurnally. Rhythmic levels are critical for the
CC generation of circadian rhythms in central as well as peripheral
CC clocks. Targeted degradation of PER and CRY proteins enables the
CC reactivation of CLOCK-ARTNL/BMAL1, thus initiating a new circadian
CC transcriptional cycle with an intrinsic period of 24 hours.
CC {ECO:0000269|PubMed:14750904}.
CC -!- PTM: Acetylated. Deacetylated by SIRT1, resulting in decreased protein
CC stability. Deacetylated by SIRT6, preventing its degradation by the
CC proteasome, resulting in increased protein stability.
CC {ECO:0000250|UniProtKB:O54943}.
CC -!- PTM: Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in
CC PER2 protein degradation. May be dephosphorylated by PP1.
CC {ECO:0000269|PubMed:11165242, ECO:0000269|PubMed:11232563}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC Ubiquitination may be inhibited by CRY1.
CC {ECO:0000250|UniProtKB:O54943}.
CC -!- DISEASE: Advanced sleep phase syndrome, familial, 1 (FASPS1)
CC [MIM:604348]: A disorder characterized by very early sleep onset and
CC offset. Individuals are 'morning larks' with a 4 hours advance of the
CC sleep, temperature and melatonin rhythms.
CC {ECO:0000269|PubMed:11232563}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20804.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB012614; BAA83709.1; -; mRNA.
DR EMBL; EF015905; ABM64216.1; -; Genomic_DNA.
DR EMBL; AB002345; BAA20804.2; ALT_INIT; mRNA.
DR EMBL; AC012485; AAX88976.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW71155.1; -; Genomic_DNA.
DR EMBL; AY647991; AAT68170.1; -; Genomic_DNA.
DR CCDS; CCDS2528.1; -. [O15055-1]
DR RefSeq; NP_073728.1; NM_022817.2. [O15055-1]
DR RefSeq; XP_005246168.1; XM_005246111.4. [O15055-1]
DR RefSeq; XP_006712887.1; XM_006712824.3. [O15055-1]
DR PDB; 6OF7; X-ray; 3.11 A; B=1093-1212.
DR PDBsum; 6OF7; -.
DR AlphaFoldDB; O15055; -.
DR SMR; O15055; -.
DR BioGRID; 114387; 149.
DR ComplexPortal; CPX-3219; Cry1-Per2 complex.
DR ComplexPortal; CPX-3220; Cry2-Per2 complex.
DR DIP; DIP-38051N; -.
DR IntAct; O15055; 10.
DR STRING; 9606.ENSP00000254657; -.
DR BindingDB; O15055; -.
DR ChEMBL; CHEMBL3751648; -.
DR GlyGen; O15055; 10 sites, 1 O-linked glycan (10 sites).
DR iPTMnet; O15055; -.
DR PhosphoSitePlus; O15055; -.
DR BioMuta; PER2; -.
DR EPD; O15055; -.
DR jPOST; O15055; -.
DR MassIVE; O15055; -.
DR MaxQB; O15055; -.
DR PaxDb; O15055; -.
DR PeptideAtlas; O15055; -.
DR PRIDE; O15055; -.
DR ProteomicsDB; 48405; -. [O15055-1]
DR ProteomicsDB; 48406; -. [O15055-2]
DR Antibodypedia; 34500; 411 antibodies from 34 providers.
DR DNASU; 8864; -.
DR Ensembl; ENST00000254657.8; ENSP00000254657.3; ENSG00000132326.12. [O15055-1]
DR GeneID; 8864; -.
DR KEGG; hsa:8864; -.
DR MANE-Select; ENST00000254657.8; ENSP00000254657.3; NM_022817.3; NP_073728.1.
DR UCSC; uc002vyc.4; human. [O15055-1]
DR CTD; 8864; -.
DR DisGeNET; 8864; -.
DR GeneCards; PER2; -.
DR HGNC; HGNC:8846; PER2.
DR HPA; ENSG00000132326; Low tissue specificity.
DR MalaCards; PER2; -.
DR MIM; 603426; gene.
DR MIM; 604348; phenotype.
DR neXtProt; NX_O15055; -.
DR OpenTargets; ENSG00000132326; -.
DR Orphanet; 164736; Familial advanced sleep-phase syndrome.
DR PharmGKB; PA33185; -.
DR VEuPathDB; HostDB:ENSG00000132326; -.
DR eggNOG; KOG3753; Eukaryota.
DR GeneTree; ENSGT00940000156342; -.
DR HOGENOM; CLU_006667_0_0_1; -.
DR InParanoid; O15055; -.
DR OMA; ESQPCSV; -.
DR OrthoDB; 145617at2759; -.
DR PhylomeDB; O15055; -.
DR TreeFam; TF318445; -.
DR PathwayCommons; O15055; -.
DR Reactome; R-HSA-400253; Circadian Clock.
DR SignaLink; O15055; -.
DR SIGNOR; O15055; -.
DR BioGRID-ORCS; 8864; 17 hits in 1079 CRISPR screens.
DR ChiTaRS; PER2; human.
DR GeneWiki; PER2; -.
DR GenomeRNAi; 8864; -.
DR Pharos; O15055; Tchem.
DR PRO; PR:O15055; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O15055; protein.
DR Bgee; ENSG00000132326; Expressed in oocyte and 212 other tissues.
DR ExpressionAtlas; O15055; baseline and differential.
DR Genevisible; O15055; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IBA:GO_Central.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0097167; P:circadian regulation of translation; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; TAS:ProtInc.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB.
DR GO; GO:0019249; P:lactate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0070345; P:negative regulation of fat cell proliferation; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0051946; P:regulation of glutamate uptake involved in transmission of nerve impulse; ISS:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0019229; P:regulation of vasoconstriction; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB.
DR CDD; cd00130; PAS; 1.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013655; PAS_fold_3.
DR InterPro; IPR022728; Period_circadian-like_C.
DR Pfam; PF08447; PAS_3; 1.
DR Pfam; PF12114; Period_C; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Cytoplasm; Disease variant; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..1255
FT /note="Period circadian protein homolog 2"
FT /id="PRO_0000162630"
FT DOMAIN 181..248
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 321..387
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 395..438
FT /note="PAC"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..484
FT /note="Important for protein stability"
FT /evidence="ECO:0000250|UniProtKB:Q9Z301"
FT REGION 512..717
FT /note="CSNK1E binding domain"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT REGION 617..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 888..1071
FT /note="Interaction with PPARG"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT REGION 931..985
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1018..1050
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1077..1106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1155..1255
FT /note="CRY binding domain"
FT /evidence="ECO:0000250|UniProtKB:Q9Z301"
FT REGION 1231..1255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 111..120
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 308..312
FT /note="LXXLL"
FT MOTIF 462..471
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 789..805
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 989..996
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 1057..1061
FT /note="LXXLL"
FT COMPBIAS 28..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..503
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..539
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 767..788
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 931..953
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1235..1255
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 530
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11232563"
FT MOD_RES 696
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 700
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 766
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 945
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 977
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 1124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT VAR_SEQ 349..404
FT /note="RAVPLLGYLPQDLIETPVLVQLHPSDRPLMLAIHKKILQSGGQPFDYSPIRF
FT RARN -> SPAVRRAAFRLFSHSVSRPERRVHHVGHQLVQLHQPMEQENLLHHWEAQSQ
FT GGPFE (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_021653"
FT VAR_SEQ 405..1255
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_021654"
FT VARIANT 5
FT /note="A -> S (in dbSNP:rs35572922)"
FT /id="VAR_051575"
FT VARIANT 662
FT /note="S -> G (in FASPS1; reduced in vitro phosphorylation
FT by CSNK1E; dbSNP:rs121908635)"
FT /evidence="ECO:0000269|PubMed:11232563"
FT /id="VAR_029080"
FT VARIANT 729
FT /note="V -> I (in dbSNP:rs4429421)"
FT /id="VAR_051576"
FT VARIANT 823
FT /note="L -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036041"
FT VARIANT 903
FT /note="V -> I (in dbSNP:rs35333999)"
FT /id="VAR_051577"
FT VARIANT 949
FT /note="F -> Y (in dbSNP:rs35998480)"
FT /id="VAR_051578"
FT VARIANT 1244
FT /note="G -> E (in dbSNP:rs934945)"
FT /id="VAR_024558"
FT MUTAGEN 662
FT /note="S->D: Restores CSNK1E-dependent phosphorylation of
FT variant G-662."
FT /evidence="ECO:0000269|PubMed:11232563"
FT HELIX 1136..1140
FT /evidence="ECO:0007829|PDB:6OF7"
FT TURN 1145..1149
FT /evidence="ECO:0007829|PDB:6OF7"
FT HELIX 1158..1171
FT /evidence="ECO:0007829|PDB:6OF7"
FT HELIX 1181..1188
FT /evidence="ECO:0007829|PDB:6OF7"
FT HELIX 1192..1196
FT /evidence="ECO:0007829|PDB:6OF7"
FT TURN 1201..1203
FT /evidence="ECO:0007829|PDB:6OF7"
SQ SEQUENCE 1255 AA; 136579 MW; 2AEF2C6BD4B6CBB0 CRC64;
MNGYAEFPPS PSNPTKEPVE PQPSQVPLQE DVDMSSGSSG HETNENCSTG RDSQGSDCDD
SGKELGMLVE PPDARQSPDT FSLMMAKSEH NPSTSGCSSD QSSKVDTHKE LIKTLKELKV
HLPADKKAKG KASTLATLKY ALRSVKQVKA NEEYYQLLMS SEGHPCGADV PSYTVEEMES
VTSEHIVKNA DMFAVAVSLV SGKILYISDQ VASIFHCKRD AFSDAKFVEF LAPHDVGVFH
SFTSPYKLPL WSMCSGADSF TQECMEEKSF FCRVSVRKSH ENEIRYHPFR MTPYLVKVRD
QQGAESQLCC LLLAERVHSG YEAPRIPPEK RIFTTTHTPN CLFQDVDERA VPLLGYLPQD
LIETPVLVQL HPSDRPLMLA IHKKILQSGG QPFDYSPIRF RARNGEYITL DTSWSSFINP
WSRKISFIIG RHKVRVGPLN EDVFAAHPCT EEKALHPSIQ ELTEQIHRLL LQPVPHSGSS
GYGSLGSNGS HEHLMSQTSS SDSNGHEDSR RRRAEICKNG NKTKNRSHYS HESGEQKKKS
VTEMQTNPPA EKKAVPAMEK DSLGVSFPEE LACKNQPTCS YQQISCLDSV IRYLESCNEA
ATLKRKCEFP ANVPALRSSD KRKATVSPGP HAGEAEPPSR VNSRTGVGTH LTSLALPGKA
ESVASLTSQC SYSSTIVHVG DKKPQPELEM VEDAASGPES LDCLAGPALA CGLSQEKEPF
KKLGLTKEVL AAHTQKEEQS FLQKFKEIRK LSIFQSHCHY YLQERSKGQP SERTAPGLRN
TSGIDSPWKK TGKNRKLKSK RVKPRDSSES TGSGGPVSAR PPLVGLNATA WSPSDTSQSS
CPAVPFPAPV PAAYSLPVFP APGTVAAPPA PPHASFTVPA VPVDLQHQFA VQPPPFPAPL
APVMAFMLPS YSFPSGTPNL PQAFFPSQPQ FPSHPTLTSE MASASQPEFP SRTSIPRQPC
ACPATRATPP SAMGRASPPL FQSRSSSPLQ LNLLQLEEAP EGGTGAMGTT GATETAAVGA
DCKPGTSRDQ QPKAPLTRDE PSDTQNSDAL STSSGLLNLL LNEDLCSASG SAASESLGSG
SLGCDASPSG AGSSDTSHTS KYFGSIDSSE NNHKAKMNTG MEESEHFIKC VLQDPIWLLM
ADADSSVMMT YQLPSRNLEA VLKEDREKLK LLQKLQPRFT ESQKQELREV HQWMQTGGLP
AAIDVAECVY CENKEKGNIC IPYEEDIPSL GLSEVSDTKE DENGSPLNHR IEEQT
