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O70361

- PER3_MOUSE

UniProt

O70361 - PER3_MOUSE

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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

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
Complete GO annotation...

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.4 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

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.
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.
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.

Family & Domainsi

Domains and Repeats

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

Region

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

Motif

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

Compositional bias

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

Sequence similaritiesi

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti967 – 9671Q → H in AAC40147. 1 Publication
Sequence conflicti1107 – 11071H → R in AAC40147. 1 Publication

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.
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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 115 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

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