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O70361

- PER3_MOUSE

UniProt

O70361 - PER3_MOUSE

Protein

Period circadian protein homolog 3

Gene

Per3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Originally described as a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance. In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters. Can bind heme.3 Publications

    GO - Molecular functioni

    1. kinase binding Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. signal transducer activity Source: InterPro
    4. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. circadian regulation of gene expression Source: InterPro
    2. circadian rhythm Source: MGI
    3. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    4. regulation of circadian sleep/wake cycle, sleep Source: UniProtKB
    5. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Biological processi

    Biological rhythms, Transcription, Transcription regulation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Period circadian protein homolog 3
    Short name:
    mPER3
    Alternative name(s):
    Circadian clock protein PERIOD 3
    Gene namesi
    Name:Per3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:1277134. Per3.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Mainly cytoplasmic. Translocates to the nucleus through binding PER1, PER2, CRY1 or CRY2, but not TIMELESS.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Animals show altered sleep and behavioral activity whitout changes in total activity or vigilance states. They have increased wheel-running activity and reduced REM (rapid eye movement) sleep and NREM (non-REM) sleep in the middle of the dark phase. At the beginning of the baseline light period, they have less wakefulness and more REM and NREM sleep. Mice spend less time in wakefulness and more time in NREM sleep on the light period immediately after sleep deprivation and REM sleep accumulates more slowly during the recovery dark phase. Double knocknouts for PER2 and PER3 show the same phenotype as PER2 knockouts with severely disrupted circadian behavior.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi359 – 3591W → E: Abolishes homodimerization. 2 Publications
    Mutagenesisi367 – 3671I → E: Abolishes homodimerization. 2 Publications
    Mutagenesisi613 – 62715SVASG…CSSTS → AVAAGIAQCACAATA: No effect on interaction with BTRC and FBXW11. 1 PublicationAdd
    BLAST

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11131113Period circadian protein homolog 3PRO_0000162634Add
    BLAST

    Post-translational modificationi

    Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus.2 Publications
    Ubiquitinated.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiO70361.

    PTM databases

    PhosphoSiteiO70361.

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed in heart, brain, lung, liver, skeletal muscle, testis, and at low level in the spleen and kidney. In brain, mainly found in the SCN, hippocampus, piriform cortex, and cerebellum. Lower level of expression in the neocortex. Expression exhibits synchronous oscillations in liver, skeletal muscle and testis.2 Publications

    Inductioni

    Exhibits circadian oscillation expression in SCN, liver, skeletal muscle, testis and eyes. In the SCN, highest levels during subjective day at CT6 and CT9, lowest levels at night, CT15, CT18 and CT 21. In the liver, skeletal muscle, testis and eyes highest levels at CT15, CT15-CT18, CT9 and CT15, and CT9-CT15, respectively. During subjective night, unresponsive to light exposure.3 Publications

    Gene expression databases

    ArrayExpressiO70361.
    BgeeiO70361.
    CleanExiMM_PER3.
    GenevestigatoriO70361.

    Interactioni

    Subunit structurei

    Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with PER1, PER2, CRY1, CRY2, and TIMELESS; interaction with CRY1 and CRY2 is weak and not rhythmic. Interacts with FBXW11 and BTRC.6 Publications

    Protein-protein interaction databases

    BioGridi202113. 7 interactions.
    DIPiDIP-60820N.
    STRINGi10090.ENSMUSP00000099493.

    Structurei

    Secondary structure

    1
    1113
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni114 – 1185
    Helixi122 – 1254
    Beta strandi131 – 1377
    Turni138 – 1403
    Beta strandi142 – 1465
    Helixi150 – 1534
    Helixi158 – 1625
    Helixi166 – 1694
    Helixi172 – 1743
    Helixi175 – 1817
    Turni184 – 1863
    Beta strandi208 – 2125
    Beta strandi218 – 2203
    Beta strandi224 – 23411
    Beta strandi239 – 2413
    Beta strandi245 – 2539
    Beta strandi259 – 2613
    Helixi265 – 2673
    Beta strandi269 – 2746
    Beta strandi278 – 2836
    Helixi287 – 2915
    Helixi295 – 2984
    Helixi303 – 3064
    Turni309 – 3135
    Helixi314 – 32411
    Turni325 – 3273
    Beta strandi336 – 3394
    Beta strandi345 – 35612
    Beta strandi358 – 3603
    Beta strandi363 – 37210
    Beta strandi377 – 3793
    Helixi394 – 40613

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4DJ3X-ray2.50A/B108-411[»]
    ProteinModelPortaliO70361.
    SMRiO70361. Positions 40-411.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini120 – 18768PAS 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini258 – 32467PAS 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini333 – 37644PACAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni551 – 750200CSNK1E binding domainAdd
    BLAST
    Regioni1035 – 111379CRY binding domainBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi54 – 6310Nuclear export signal 1By similarity
    Motifi399 – 40810Nuclear export signal 3By similarity
    Motifi719 – 73517Nuclear localization signalBy similarityAdd
    BLAST
    Motifi913 – 9208Nuclear export signal 2By similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi562 – 5654Poly-Ser

    Sequence similaritiesi

    Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG269786.
    GeneTreeiENSGT00510000046467.
    HOVERGENiHBG008167.
    InParanoidiA2A894.
    KOiK02633.
    OMAiFKHVGLT.
    OrthoDBiEOG7S7SD0.
    TreeFamiTF318445.

    Family and domain databases

    InterProiIPR001610. PAC.
    IPR000014. PAS.
    IPR015524. Per_circ_prot_3.
    IPR022728. Period_circadian-like_C.
    [Graphical view]
    PANTHERiPTHR11269:SF13. PTHR11269:SF13. 1 hit.
    PfamiPF12114. Period_C. 1 hit.
    [Graphical view]
    SMARTiSM00086. PAC. 1 hit.
    SM00091. PAS. 2 hits.
    [Graphical view]
    SUPFAMiSSF55785. SSF55785. 1 hit.
    PROSITEiPS50112. PAS. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O70361-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDPCGDPAVP GGDCPQTRGP GLQGASGQEG PLQGTCVDSS HSEHEDRNRM     50
    SEELIMVVQE MKKYFPAERH TKPSTLDALN YALRCVHSVQ ANSDFFQSLG 100
    PRGAHQADVT VYSLEDLTAL ASEHTSKNTD TFAAVFSFLS GRLVHISEQA 150
    ALILNSKRGF LKSVHFVDLL APQDVRAFYA HTAPTQLPFW NNWTQRASQY 200
    ECAPAKPFFC RICGGGDREK RHYSPFRILP YLVHVHSSAQ PEPEPCCLTL 250
    VEKIHSGYEA PRIPVDKRIF TTTHTPGCVF LEVDERAVPL LGYLPQDLIG 300
    TSILTYLHPE DRPLMVAIHQ KVLKYAGHPP FEHSPVRFCT QNGEYVILDS 350
    SWSSFVNPWS RKVSFIIGRH KVRTSPLNED VFATRIKKAA SNDKDIAELQ 400
    EQIHKLLLQP VHASASSGYG SLGSSGSQEQ HVSITSSSES SGHCPEEGQH 450
    EQMTLQQVYA SVNKIKNVGQ QLYIESMARS SVKPVAETCV EPQGGDEQKD 500
    FSSSQTLKNK STTDTGSGGN LQQEQPSSSY QQMNCIDSVI RYLTSYSLPA 550
    LKRKCISCTN TSSSSEEAKP IPEVDSSQRD TEQLLDIRKQ ETTGPSTDIE 600
    GGAARTLSTA ALSVASGISQ CSCSSTSGHA PPLQSESVAV ACKPWALRTK 650
    ASHLAAGGFK HVGLTAAVLS AHTQKEEQNY VDRFREKILT SPYGCYLQQE 700
    SRNRAQYSCV QAGSTAKHSR CAGSERQKHK RKKLPAPVDT SSPGAHLCPH 750
    VTGLLPDEQH WGPSASPSPL GAGLAFPSAL VVPSQTPYLL PSFPLQDMAS 800
    QGVGVSAAWG AAAGCPPLSA GPQAVAAFPS AYVDTLMTIF LHNAPLFPLW 850
    PPSFSPYPSL GAAGSSELAP LVPAMAPNPE PTTSGHSQRR VEENWEAHSE 900
    ELPFISSRSS SPLQLNLLQE EMPAPSESAD AVRRGAGPDA KHHCVTGPSG 950
    SRSRHCTSGE LATATAQQES AAASGSSASS IYFSSTDYAS EVSENRQRPQ 1000
    DRQRDEALPG AAEESIWRMI ERTPECVLMT YQVPERGREE VLKQDLEKLQ 1050
    SMEQQQPLFS PAQREELAKV RSWIHSHTAP QEGHLQSCVA CEDRGSVGDT 1100
    AEVLEQHPAE DTS 1113
    Length:1,113
    Mass (Da):120,911
    Last modified:July 27, 2011 - v2
    Checksum:i99B06113BAB743C7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti967 – 9671Q → H in AAC40147. (PubMed:9655499)Curated
    Sequence conflicti1107 – 11071H → R in AAC40147. (PubMed:9655499)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF050182 mRNA. Translation: AAC40147.1.
    AL607143 Genomic DNA. Translation: CAM24786.1.
    CCDSiCCDS18978.1.
    PIRiT14260.
    RefSeqiNP_035197.2. NM_011067.3.
    UniGeneiMm.121361.

    Genome annotation databases

    EnsembliENSMUST00000103204; ENSMUSP00000099493; ENSMUSG00000028957.
    GeneIDi18628.
    KEGGimmu:18628.
    UCSCiuc008vye.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF050182 mRNA. Translation: AAC40147.1 .
    AL607143 Genomic DNA. Translation: CAM24786.1 .
    CCDSi CCDS18978.1.
    PIRi T14260.
    RefSeqi NP_035197.2. NM_011067.3.
    UniGenei Mm.121361.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4DJ3 X-ray 2.50 A/B 108-411 [» ]
    ProteinModelPortali O70361.
    SMRi O70361. Positions 40-411.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202113. 7 interactions.
    DIPi DIP-60820N.
    STRINGi 10090.ENSMUSP00000099493.

    PTM databases

    PhosphoSitei O70361.

    Proteomic databases

    PRIDEi O70361.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000103204 ; ENSMUSP00000099493 ; ENSMUSG00000028957 .
    GeneIDi 18628.
    KEGGi mmu:18628.
    UCSCi uc008vye.1. mouse.

    Organism-specific databases

    CTDi 8863.
    MGIi MGI:1277134. Per3.

    Phylogenomic databases

    eggNOGi NOG269786.
    GeneTreei ENSGT00510000046467.
    HOVERGENi HBG008167.
    InParanoidi A2A894.
    KOi K02633.
    OMAi FKHVGLT.
    OrthoDBi EOG7S7SD0.
    TreeFami TF318445.

    Miscellaneous databases

    NextBioi 294584.
    PROi O70361.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O70361.
    Bgeei O70361.
    CleanExi MM_PER3.
    Genevestigatori O70361.

    Family and domain databases

    InterProi IPR001610. PAC.
    IPR000014. PAS.
    IPR015524. Per_circ_prot_3.
    IPR022728. Period_circadian-like_C.
    [Graphical view ]
    PANTHERi PTHR11269:SF13. PTHR11269:SF13. 1 hit.
    Pfami PF12114. Period_C. 1 hit.
    [Graphical view ]
    SMARTi SM00086. PAC. 1 hit.
    SM00091. PAS. 2 hits.
    [Graphical view ]
    SUPFAMi SSF55785. SSF55785. 1 hit.
    PROSITEi PS50112. PAS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain."
      Zylka M.J., Shearman L.P., Weaver D.R., Reppert S.M.
      Neuron 20:1103-1110(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
      Strain: C57BL/6.
      Tissue: Brain.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop."
      Kume K., Zylka M.J., Sriram S., Shearman L.P., Weaver D.R., Jin X., Maywood E.S., Hastings M.H., Reppert S.M.
      Cell 98:193-205(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: HOMODIMERIZATION, INTERACTION WITH PER1; PER2; CRY1 AND CRY2, SUBCELLULAR LOCATION.
    4. Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL.
    5. "Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock."
      Bae K., Jin X., Maywood E.S., Hastings M.H., Reppert S.M., Weaver D.R.
      Neuron 30:525-536(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CIRCADIAN RHYTHMS, DISRUPTION PHENOTYPE.
    6. "Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells."
      Akashi M., Tsuchiya Y., Yoshino T., Nishida E.
      Mol. Cell. Biol. 22:1693-1703(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CSNK1D AND CSNK1E, PHOSPHORYLATION, UBIQUITINATION, SUBCELLULAR LOCATION.
    7. Cited for: INTERACTION WITH TIMELESS, INDUCTION.
    8. "Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock."
      Lee C., Weaver D.R., Reppert S.M.
      Mol. Cell. Biol. 24:584-594(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PER1; PER2; CRY1 AND CRY2, PHOSPHORYLATION, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
    9. "SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein."
      Shirogane T., Jin J., Ang X.L., Harper J.W.
      J. Biol. Chem. 280:26863-26872(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FBXW11 AND BTRC, MUTAGENESIS OF 613-S--S-627.
    10. "Altered sleep and behavioral activity phenotypes in PER3-deficient mice."
      Hasan S., van der Veen D.R., Winsky-Sommerer R., Dijk D.J., Archer S.N.
      Am. J. Physiol. 301:R1821-R1830(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN SLEEP HOMEOSTASIS, DISRUPTION PHENOTYPE.
    11. "Metabolism and the circadian clock converge."
      Eckel-Mahan K., Sassone-Corsi P.
      Physiol. Rev. 93:107-135(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    12. "Molecular architecture of the mammalian circadian clock."
      Partch C.L., Green C.B., Takahashi J.S.
      Trends Cell Biol. 24:90-99(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    13. "Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function."
      Kucera N., Schmalen I., Hennig S., Ollinger R., Strauss H.M., Grudziecki A., Wieczorek C., Kramer A., Wolf E.
      Proc. Natl. Acad. Sci. U.S.A. 109:3311-3316(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 108-411, FUNCTION IN HEME BINDING, SUBUNIT, MUTAGENESIS OF TRP-359 AND ILE-367.

    Entry informationi

    Entry nameiPER3_MOUSE
    AccessioniPrimary (citable) accession number: O70361
    Secondary accession number(s): A2A894
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 116 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3