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O70361 (PER3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Period circadian protein homolog 3

Short name=mPER3
Alternative name(s):
Circadian clock protein PERIOD 3
Gene names
Name:Per3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1113 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.10 Ref.13

Subunit structure

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. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.13

Subcellular location

Cytoplasm. Nucleus. Note: Mainly cytoplasmic. Translocates to the nucleus through binding PER1, PER2, CRY1 or CRY2, but not TIMELESS. Ref.3 Ref.4 Ref.6 Ref.8

Tissue specificity

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. Ref.1 Ref.8

Induction

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. Ref.1 Ref.7 Ref.8

Post-translational modification

Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus.

Ubiquitinated. Ref.6

Disruption phenotype

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. Ref.5 Ref.10

Sequence similarities

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11131113Period circadian protein homolog 3
PRO_0000162634

Regions

Domain120 – 18768PAS 1
Domain258 – 32467PAS 2
Domain333 – 37644PAC
Region551 – 750200CSNK1E binding domain
Region1035 – 111379CRY binding domain By similarity
Motif54 – 6310Nuclear export signal 1 By similarity
Motif399 – 40810Nuclear export signal 3 By similarity
Motif719 – 73517Nuclear localization signal By similarity
Motif913 – 9208Nuclear export signal 2 By similarity
Compositional bias562 – 5654Poly-Ser

Experimental info

Mutagenesis3591W → E: Abolishes homodimerization. Ref.9 Ref.13
Mutagenesis3671I → E: Abolishes homodimerization. Ref.9 Ref.13
Mutagenesis613 – 62715SVASG…CSSTS → AVAAGIAQCACAATA: No effect on interaction with BTRC and FBXW11. Ref.9
Sequence conflict9671Q → H in AAC40147. Ref.1
Sequence conflict11071H → R in AAC40147. Ref.1

Secondary structure

............................................................. 1113
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O70361 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 99B06113BAB743C7

FASTA1,113120,911
        10         20         30         40         50         60 
MDPCGDPAVP GGDCPQTRGP GLQGASGQEG PLQGTCVDSS HSEHEDRNRM SEELIMVVQE 

        70         80         90        100        110        120 
MKKYFPAERH TKPSTLDALN YALRCVHSVQ ANSDFFQSLG PRGAHQADVT VYSLEDLTAL 

       130        140        150        160        170        180 
ASEHTSKNTD TFAAVFSFLS GRLVHISEQA ALILNSKRGF LKSVHFVDLL APQDVRAFYA 

       190        200        210        220        230        240 
HTAPTQLPFW NNWTQRASQY ECAPAKPFFC RICGGGDREK RHYSPFRILP YLVHVHSSAQ 

       250        260        270        280        290        300 
PEPEPCCLTL VEKIHSGYEA PRIPVDKRIF TTTHTPGCVF LEVDERAVPL LGYLPQDLIG 

       310        320        330        340        350        360 
TSILTYLHPE DRPLMVAIHQ KVLKYAGHPP FEHSPVRFCT QNGEYVILDS SWSSFVNPWS 

       370        380        390        400        410        420 
RKVSFIIGRH KVRTSPLNED VFATRIKKAA SNDKDIAELQ EQIHKLLLQP VHASASSGYG 

       430        440        450        460        470        480 
SLGSSGSQEQ HVSITSSSES SGHCPEEGQH EQMTLQQVYA SVNKIKNVGQ QLYIESMARS 

       490        500        510        520        530        540 
SVKPVAETCV EPQGGDEQKD FSSSQTLKNK STTDTGSGGN LQQEQPSSSY QQMNCIDSVI 

       550        560        570        580        590        600 
RYLTSYSLPA LKRKCISCTN TSSSSEEAKP IPEVDSSQRD TEQLLDIRKQ ETTGPSTDIE 

       610        620        630        640        650        660 
GGAARTLSTA ALSVASGISQ CSCSSTSGHA PPLQSESVAV ACKPWALRTK ASHLAAGGFK 

       670        680        690        700        710        720 
HVGLTAAVLS AHTQKEEQNY VDRFREKILT SPYGCYLQQE SRNRAQYSCV QAGSTAKHSR 

       730        740        750        760        770        780 
CAGSERQKHK RKKLPAPVDT SSPGAHLCPH VTGLLPDEQH WGPSASPSPL GAGLAFPSAL 

       790        800        810        820        830        840 
VVPSQTPYLL PSFPLQDMAS QGVGVSAAWG AAAGCPPLSA GPQAVAAFPS AYVDTLMTIF 

       850        860        870        880        890        900 
LHNAPLFPLW PPSFSPYPSL GAAGSSELAP LVPAMAPNPE PTTSGHSQRR VEENWEAHSE 

       910        920        930        940        950        960 
ELPFISSRSS SPLQLNLLQE EMPAPSESAD AVRRGAGPDA KHHCVTGPSG SRSRHCTSGE 

       970        980        990       1000       1010       1020 
LATATAQQES AAASGSSASS IYFSSTDYAS EVSENRQRPQ DRQRDEALPG AAEESIWRMI 

      1030       1040       1050       1060       1070       1080 
ERTPECVLMT YQVPERGREE VLKQDLEKLQ SMEQQQPLFS PAQREELAKV RSWIHSHTAP 

      1090       1100       1110 
QEGHLQSCVA CEDRGSVGDT AEVLEQHPAE DTS 

« Hide

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"Nuclear export of mammalian PERIOD proteins."
Vielhaber E.L., Duricka D., Ullman K.S., Virshup D.M.
J. Biol. Chem. 276:45921-45927(2001) [PubMed] [Europe PMC] [Abstract]
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]"Requirement of mammalian Timeless for circadian rhythmicity."
Barnes J.W., Tischkau S.A., Barnes J.A., Mitchell J.W., Burgoon P.W., Hickok J.R., Gillette M.U.
Science 302:439-442(2003) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF050182 mRNA. Translation: AAC40147.1.
AL607143 Genomic DNA. Translation: CAM24786.1.
CCDSCCDS18978.1.
PIRT14260.
RefSeqNP_035197.2. NM_011067.3.
UniGeneMm.121361.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DJ3X-ray2.50A/B108-411[»]
ProteinModelPortalO70361.
SMRO70361. Positions 40-411.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202113. 7 interactions.
STRING10090.ENSMUSP00000099493.

PTM databases

PhosphoSiteO70361.

Proteomic databases

PRIDEO70361.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000103204; ENSMUSP00000099493; ENSMUSG00000028957.
GeneID18628.
KEGGmmu:18628.
UCSCuc008vye.1. mouse.

Organism-specific databases

CTD8863.
MGIMGI:1277134. Per3.

Phylogenomic databases

eggNOGNOG269786.
GeneTreeENSGT00510000046467.
HOVERGENHBG008167.
InParanoidA2A894.
KOK02633.
OMAFKHVGLT.
OrthoDBEOG7S7SD0.
TreeFamTF318445.

Gene expression databases

ArrayExpressO70361.
BgeeO70361.
CleanExMM_PER3.
GenevestigatorO70361.

Family and domain databases

InterProIPR001610. PAC.
IPR000014. PAS.
IPR015524. Per_circ_prot_3.
IPR022728. Period_circadian-like_C.
[Graphical view]
PANTHERPTHR11269:SF13. PTHR11269:SF13. 1 hit.
PfamPF12114. Period_C. 1 hit.
[Graphical view]
SMARTSM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF55785. SSF55785. 1 hit.
PROSITEPS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294584.
PROO70361.
SOURCESearch...

Entry information

Entry namePER3_MOUSE
AccessionPrimary (citable) accession number: O70361
Secondary accession number(s): A2A894
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot