Gene Symbol: Per3
Description: period circadian clock 3
Alias: 2810049O06Rik, mPer3, period circadian protein homolog 3, circadian clock protein PERIOD 3, period homolog 3
Species: mouse
Products:     Per3

Top Publications

  1. Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X, et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999;98:193-205 pubmed
    ..Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. ..
  2. Zylka M, Shearman L, Weaver D, Reppert S. Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Neuron. 1998;20:1103-10 pubmed
    ..and characterized the mouse cDNA of a third mammalian homolog of the Drosophila period gene and designated it mPer3. The mPER3 protein shows approximately 37% amino acid identity with mPER1 and mPER2 proteins...
  3. Jin X, Shearman L, Weaver D, Zylka M, de Vries G, Reppert S. A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell. 1999;96:57-68 pubmed
    ..These data indicate that the transcriptional machinery of the core clockwork directly regulates a clock-controlled output rhythm. ..
  4. van der Veen D, Archer S. Light-dependent behavioral phenotypes in PER3-deficient mice. J Biol Rhythms. 2010;25:3-8 pubmed publisher
    A functional knockout of Period3 in mice (mPer3(-/-)) results in a mildly altered circadian phenotype, and mPer3 shows a redundant role within the circadian clock...
  5. Pendergast J, Friday R, Yamazaki S. Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis. PLoS ONE. 2010;5:e8552 pubmed publisher
    ..luciferase expression (Per1-luc) in cultured SCN, pituitary, and lung explants from Per2(-/-) and Per3(-/-) mice congenic with the C57BL/6J strain...
  6. Kwak E, Kim T, Kim K. Essential role of 3'-untranslated region-mediated mRNA decay in circadian oscillations of mouse Period3 mRNA. J Biol Chem. 2006;281:19100-6 pubmed
    ..the roles of post-transcriptional regulations, we focused on the 3'-untranslated region (3'-UTR) of mouse Period3 (mPer3) mRNA, one of the clock genes...
  7. Dudley C, Erbel Sieler C, Estill S, Reick M, Franken P, Pitts S, et al. Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science. 2003;301:379-83 pubmed
    ..Our results indicate that NPAS2 plays a substantive role in maintaining circadian behaviors in normal LD and feeding conditions and that NPAS2 is critical for adaptability to food restriction. ..
  8. Pendergast J, Friday R, Yamazaki S. Photic entrainment of period mutant mice is predicted from their phase response curves. J Neurosci. 2010;30:12179-84 pubmed publisher
    ..we constructed phase response curves (PRC) to light pulses for C57BL/6J wild-type, Per1(-/-), Per2(-/-), and Per3(-/-) mice and tested whether the PRCs accurately predict entrainment to non-24 light-dark cycles (T-cycles) and ..
  9. Bae K, Jin X, Maywood E, Hastings M, Reppert S, Weaver D. Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron. 2001;30:525-36 pubmed
    ..Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively,..

More Information


  1. Pendergast J, Niswender K, Yamazaki S. Tissue-specific function of Period3 in circadian rhythmicity. PLoS ONE. 2012;7:e30254 pubmed publisher
    ..and light responsiveness in the master circadian clock in the suprachiasmatic nuclei (SCN), the function of Per3 has been elusive...
  2. Hasan S, van der Veen D, Winsky Sommerer R, Dijk D, Archer S. Altered sleep and behavioral activity phenotypes in PER3-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2011;301:R1821-30 pubmed publisher
    ..The clock gene Period3 (Per3) has a redundant function within the circadian system and is associated with sleep homeostasis in humans...
  3. Costa M, So A, Kaasik K, Krueger K, Pillsbury M, Fu Y, et al. Circadian rhythm gene period 3 is an inhibitor of the adipocyte cell fate. J Biol Chem. 2011;286:9063-70 pubmed publisher
    ..Here we showed that glucocorticoids repressed Per3 expression and that this repression was critical for advancing mesenchymal stem cells to the adipocyte fate...
  4. Shearman L, Jin X, Lee C, Reppert S, Weaver D. Targeted disruption of the mPer3 gene: subtle effects on circadian clock function. Mol Cell Biol. 2000;20:6269-75 pubmed
    ..To assess the role of mouse PER3 (mPER3) in the circadian timing system, we generated mice with a targeted disruption of the mPer3 gene...
  5. Shiromani P, Xu M, Winston E, Shiromani S, Gerashchenko D, Weaver D. Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. Am J Physiol Regul Integr Comp Physiol. 2004;287:R47-57 pubmed
    ..significant differences in waking, slow-wave sleep (SWS), or rapid eye movement (REM) sleep between mPer1, mPer2, mPer3, mPer1-mPer2 double-mutant, and wild-type mice...
  6. Takumi T, Taguchi K, Miyake S, Sakakida Y, Takashima N, Matsubara C, et al. A light-independent oscillatory gene mPer3 in mouse SCN and OVLT. EMBO J. 1998;17:4753-9 pubmed
    A new member of the mammalian period gene family, mPer3, was isolated and its expression pattern characterized in the mouse brain...
  7. Jenkins A, Archer S, von Schantz M. Expansion during primate radiation of a variable number tandem repeat in the coding region of the circadian clock gene period3. J Biol Rhythms. 2005;20:470-2 pubmed publisher
  8. Zylka M, Shearman L, Levine J, Jin X, Weaver D, Reppert S. Molecular analysis of mammalian timeless. Neuron. 1998;21:1115-22 pubmed
    ..The data suggest that PER-PER interactions have replaced the function of PER-TIM dimers in the molecular workings of the mammalian circadian clock. ..
  9. Dunlap J. Molecular bases for circadian clocks. Cell. 1999;96:271-90 pubmed
  10. Ramanathan C, Xu H, Khan S, Shen Y, Gitis P, Welsh D, et al. Cell type-specific functions of period genes revealed by novel adipocyte and hepatocyte circadian clock models. PLoS Genet. 2014;10:e1004244 pubmed publisher
    ..b>Per3, which has relatively modest behavioral effects in knockout mice, substantially affects period length in the three ..
  11. Wang X, Mozhui K, Li Z, Mulligan M, Ingels J, Zhou X, et al. A promoter polymorphism in the Per3 gene is associated with alcohol and stress response. Transl Psychiatry. 2012;2:e73 pubmed publisher
    The period homolog genes Per1, Per2 and Per3 are important components of the circadian clock system...
  12. Luo W, Ma S, Yang Y, Wang C, Zhang D, Zhang Q, et al. TFEB regulates PER3 expression via glucose-dependent effects on CLOCK/BMAL1. Int J Biochem Cell Biol. 2016;78:31-42 pubmed publisher
    ..A metabolic network involving PER3 raises the possibility that some metabolic regulators are directly involved in the mammalian clock...
  13. Pereira D, Van der Veen D, Gonçalves B, Tufik S, von Schantz M, Archer S, et al. The effect of different photoperiods in circadian rhythms of per3 knockout mice. Biomed Res Int. 2014;2014:170795 pubmed publisher
    ..aim of this study was to analyse the circadian behavioural responses of mice carrying a functional knockout of the Per3 gene (Per3(-/-)) to different light?:?dark (L?:?D) cycles...
  14. Sangoram A, Saez L, Antoch M, Gekakis N, Staknis D, Whiteley A, et al. Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. Neuron. 1998;21:1101-13 pubmed
    ..Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals. ..
  15. Oh hashi K, Naruse Y, Tanaka M. Intracellular calcium mobilization induces period genes via MAP kinase pathways in NIH3T3 cells. FEBS Lett. 2002;516:101-5 pubmed
    ..treatment with thapsigargin significantly induced transcripts of mouse period 1 and 2 (mPer1 and mPer2) but not mPer3 among circadian related genes in NIH3T3 cells...
  16. Santos B, Marques T, Malta M, Gameleira F, Secolin R, Andrade T, et al. PER2 rs2304672, CLOCK rs1801260, and PER3 rs57875989 polymorphisms are not associated with juvenile myoclonic epilepsy. Epilepsy Behav. 2014;36:82-5 pubmed publisher
    ..Accordingly, we investigated whether functional clock gene polymorphisms (PER2 111C>G, CLOCK 3111T>C, and PER3 VNTR) might influence the risk for JME...
  17. Hasan S, van der Veen D, Winsky Sommerer R, Hogben A, Laing E, Koentgen F, et al. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism. FASEB J. 2014;28:2441-54 pubmed publisher
    ..variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss...
  18. Zhang L, Hirano A, Hsu P, Jones C, Sakai N, Okuro M, et al. A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait. Proc Natl Acad Sci U S A. 2016;113:E1536-44 pubmed publisher
    ..We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and ..
  19. Cheng B, Anea C, Yao L, Chen F, Patel V, Merloiu A, et al. Tissue-intrinsic dysfunction of circadian clock confers transplant arteriosclerosis. Proc Natl Acad Sci U S A. 2011;108:17147-52 pubmed publisher
  20. Wang J, Lin Y, Chen H, Kong X, Xiong H, Shen N, et al. Calcium prevents tumorigenesis in a mouse model of colorectal cancer. PLoS ONE. 2011;6:e22566 pubmed publisher
    ..analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group...
  21. Brown S, Schibler U. The ins and outs of circadian timekeeping. Curr Opin Genet Dev. 1999;9:588-94 pubmed
    ..Taken together, these observations are reshaping thinking about inputs and outputs of metazoan circadian clocks. ..
  22. Fogerty J, Besharse J. 174delG mutation in mouse MFRP causes photoreceptor degeneration and RPE atrophy. Invest Ophthalmol Vis Sci. 2011;52:7256-66 pubmed publisher
    ..These mice will be useful to identify a function of MFRP and to study the pathogenesis of atrophic macular degeneration. ..
  23. Kim D, Kwak E, Kim S, Lee K, Woo K, Kim K. hnRNP Q mediates a phase-dependent translation-coupled mRNA decay of mouse Period3. Nucleic Acids Res. 2011;39:8901-14 pubmed publisher
    ..Here we demonstrate that the turnover rate of mouse Period3 (mPer3) mRNA is dramatically changed in a circadian phase-dependent manner...
  24. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output. ..
  25. Loop S, Pieler T. Nuclear import of mPER3 in Xenopus oocytes and HeLa cells requires complex formation with mPER1. FEBS J. 2005;272:3714-24 pubmed
    ..Our major finding is that nuclear import of mPER3 requires complex formation with mPER1...
  26. Yoshimura T, Suzuki Y, Makino E, Suzuki T, Kuroiwa A, Matsuda Y, et al. Molecular analysis of avian circadian clock genes. Brain Res Mol Brain Res. 2000;78:207-15 pubmed
    ..and qPER3 showed approximately 79%, approximately 46% and approximately 33% amino acid identity to mCLOCK, mPER2, mPER3, respectively. Clock was mapped to quail chromosome 4 and chicken chromosome 4q1.6-q2.1...
  27. Liu Y, Heintzen C, Loros J, Dunlap J. Regulation of clock genes. Cell Mol Life Sci. 1999;55:1195-205 pubmed
    ..Both transcriptional and posttranscriptional mechanisms appear to be important for circadian rhythm generation in all of these organisms. ..
  28. Shirogane T, Jin J, Ang X, Harper J. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem. 2005;280:26863-72 pubmed
  29. Travnickova Bendova Z, Cermakian N, Reppert S, Sassone Corsi P. Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc Natl Acad Sci U S A. 2002;99:7728-33 pubmed
    ..Whereas mPer1 and mPer2 are light-inducible in clock neurons of the hypothalamic suprachiasmatic nucleus, mPer3 is not. We have studied the promoter structure of the three mPer genes and compared their regulation...
  30. Akashi M, Tsuchiya Y, Yoshino T, Nishida E. Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells. Mol Cell Biol. 2002;22:1693-703 pubmed
    ..The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway...
  31. Takano A, Shimizu K, Kani S, Buijs R, Okada M, Nagai K. Cloning and characterization of rat casein kinase 1epsilon. FEBS Lett. 2000;477:106-12 pubmed
    ..rCK1epsilon is predominantly expressed in the brain including the SCN, binds and phosphorylates mPer1, mPer2, and mPer3 in vitro, and translocates mPer1 and mPer3, but not mPer2, to the cell nucleus depending on its kinase activity ..
  32. Pendergast J, Niswender K, Yamazaki S. The complex relationship between the light-entrainable and methamphetamine-sensitive circadian oscillators: evidence from behavioral studies of Period-mutant mice. Eur J Neurosci. 2013;38:3044-53 pubmed publisher
    ..demonstrating that no single Period gene is responsible for the short-period MASCO rhythm of Per1(-/-) /Per2(-/-) /Per3(-/-) mice...
  33. Pendergast J, Oda G, Niswender K, Yamazaki S. Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s). Proc Natl Acad Sci U S A. 2012;109:14218-23 pubmed publisher
    ..We found that both the MASCO and FEO in Per1(-/-)/Per2(-/-)/Per3(-/-) mice are circadian oscillators with unusually short (?21 h) periods...
  34. Xu Y, Guo W, Li P, Zhang Y, Zhao M, Fan Z, et al. Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression. PLoS Genet. 2016;12:e1005992 pubmed publisher
    ..This study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure. ..
  35. Wang Y, Pati P, Xu Y, Chen F, Stepp D, Huo Y, et al. Endotoxin Disrupts Circadian Rhythms in Macrophages via Reactive Oxygen Species. PLoS ONE. 2016;11:e0155075 pubmed publisher
    ..These results suggest that pro-inflammatory stimuli can disrupt circadian rhythms in macrophages and that impaired circadian rhythms may contribute to cardiovascular diseases by altering macrophage behavior. ..
  36. Anea C, Ali M, Osmond J, Sullivan J, Stepp D, Merloiu A, et al. Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice. Arterioscler Thromb Vasc Biol. 2010;30:2535-43 pubmed publisher
    ..Circadian clock dysfunction contributes to hardening of arteries, which may involve impaired control of the extracellular matrix composition. ..
  37. Gumz M, Stow L, Lynch I, Greenlee M, Rudin A, Cain B, et al. The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice. J Clin Invest. 2009;119:2423-34 pubmed publisher
    ..These results suggest a role for Period 1 in the regulation of the renal epithelial sodium channel and more broadly implicate the circadian clock in control of sodium balance. ..
  38. Climent J, Perez Losada J, Quigley D, Kim I, DelRosario R, Jen K, et al. Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. J Clin Oncol. 2010;28:3770-8 pubmed publisher
    To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development.
  39. Albrecht U, Sun Z, Eichele G, Lee C. A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light. Cell. 1997;91:1055-64 pubmed
    ..mper1, unlike period and mper2, is expressed rapidly after exposure to light at CT22. It appears that mper1 is the pacemaker component which responds to light and thus mediates photic entrainment. ..
  40. Kim S, Lee K, Kim D, Kwak E, Kim S, Kim K. Rhythmic control of mRNA stability modulates circadian amplitude of mouse Period3 mRNA. J Neurochem. 2015;132:642-56 pubmed publisher
    ..Mouse Period3 (mPer3) is one of the paralogs of Period gene and its function is important in peripheral clocks and sleep physiology...
  41. Barnes J, Tischkau S, Barnes J, Mitchell J, Burgoon P, Hickok J, et al. Requirement of mammalian Timeless for circadian rhythmicity. Science. 2003;302:439-42 pubmed
    ..These data suggest that mTim is required for rhythmicity and is a functional homolog of dTim on the negative-feedback arm of the mammalian molecular clockwork. ..
  42. Kucera N, Schmalen I, Hennig S, Ollinger R, Strauss H, Grudziecki A, et al. Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function. Proc Natl Acad Sci U S A. 2012;109:3311-6 pubmed publisher
    The three PERIOD homologues mPER1, mPER2, and mPER3 constitute central components of the mammalian circadian clock...
  43. Vielhaber E, Duricka D, Ullman K, Virshup D. Nuclear export of mammalian PERIOD proteins. J Biol Chem. 2001;276:45921-7 pubmed
    ..Similar sequences were identified in mPER2 and mPER3 as well as in several insect PER proteins...
  44. Toh K, Jones C, He Y, Eide E, Hinz W, Virshup D, et al. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science. 2001;291:1040-3 pubmed
    ..Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period. ..
  45. Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed
    The mPER1 and mPER2 proteins have important roles in the circadian clock mechanism, whereas mPER3 is expendable...
  46. Sakakida Y, Miyamoto Y, Nagoshi E, Akashi M, Nakamura T, Mamine T, et al. Importin alpha/beta mediates nuclear transport of a mammalian circadian clock component, mCRY2, together with mPER2, through a bipartite nuclear localization signal. J Biol Chem. 2005;280:13272-8 pubmed
    ..These results suggest that the importin alpha/beta system is involved in nuclear entry of mammalian clock components, which is indispensable to transcriptional oscillation of clock genes. ..