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The '''PER3''' [[gene]] encodes the '''period circadian protein homolog 3''' [[protein]] in humans.<ref name="pmid9427249">{{cite journal | vauthors = Shearman LP, Zylka MJ, Weaver DR, |
The '''PER3''' [[gene]] encodes the '''period circadian protein homolog 3''' [[protein]] in humans.<ref name="pmid9427249">{{cite journal | vauthors = Shearman LP, Zylka MJ, Weaver DR, Kolakowski LF, Reppert SM | title = Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei | journal = Neuron | volume = 19 | issue = 6 | pages = 1261–9 | date = December 1997 | pmid = 9427249 | pmc = | doi = 10.1016/S0896-6273(00)80417-1 }}</ref> |
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== Function == |
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| ⚫ | This gene is a member of the Period family of genes and is expressed in a [[circadian]] pattern in the [[suprachiasmatic nucleus]], the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the [[circadian rhythm]]s of locomotor activity, metabolism, and behavior. Circadian expression in the [[suprachiasmatic nucleus]] continues in constant darkness, and a shift in the light/dark cycle evokes a proportional shift of gene expression in the [[suprachiasmatic nucleus]]. The specific function of this gene is not yet known.<ref>{{cite web | title = Entrez Gene: PER3 period homolog 3 (Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8863| accessdate = }}</ref> |
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==Role in chronobiology== |
==Role in chronobiology== |
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The RNA levels of mPer3 oscillate with a circadian rhythm in both the SCN and in the eyes, as well as in peripheral tissues, including the liver, skeletal muscle, and testis |
The RNA levels of mPer3 oscillate with a circadian rhythm in both the SCN and in the eyes, as well as in peripheral tissues, including the liver, skeletal muscle, and testis.<ref name="Zylka 1998">{{cite journal | vauthors = Zylka MJ, Shearman LP, Weaver DR, Reppert SM | title = Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain | journal = Neuron | volume = 20 | issue = 6 | pages = 1103–10 | date = June 1998 | pmid = 9655499 | doi = 10.1016/S0896-6273(00)80492-4 }}</ref> Unlike Per1 and Per2, of which the mRNA is induced in response to light, Per3 mRNA in the SCN does not respond to light. This suggests that Per3 may be regulated differently than either Per1 or Per2.<ref name="Zylka 1998" /> |
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The mPER3 protein contains a PAS domain, similar to mPER1 and mPER2. Likely, mPER3 binds to other proteins using this domain |
The mPER3 protein contains a PAS domain, similar to mPER1 and mPER2. Likely, mPER3 binds to other proteins using this domain.<ref name="Zylka 1998" /> However, while PER1/2 have been shown to be important in the transcription-translation feedback loop involved in the intracellular circadian clock, the influence of PER3 in this loop has not yet been fully elucidated, given that mPER3 does not appear to be functionally redundant to mPER1 and mPER2.<ref name="Bae 2001">{{cite journal | vauthors = Bae K, Jin X, Maywood ES, Hastings MH, Reppert SM, Weaver DR | title = Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock | journal = Neuron | volume = 30 | issue = 2 | pages = 525–36 | date = May 2001 | pmid = 11395012 | doi = 10.1016/S0896-6273(01)00302-6 }}</ref> Researchers hypothesize that mPer3 may not be important to the core clock loop at all.<ref name="Bae 2001" /> |
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==Misconceptions== |
==Misconceptions== |
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While the Per3 gene is a paralog to the Per1 and Per2 genes, studies in animals generally show that it does not contribute significantly to circadian rhythms. Functional Per3-/- animals experience only small changes in free-running period <ref name="Bae 2001" />,and do not respond significantly differently to light pulses |
While the Per3 gene is a paralog to the Per1 and Per2 genes, studies in animals generally show that it does not contribute significantly to circadian rhythms. Functional Per3-/- animals experience only small changes in free-running period <ref name="Bae 2001" />,and do not respond significantly differently to light pulses.<ref name="Shearman 2000">{{cite journal | vauthors = Shearman LP, Jin X, Lee C, Reppert SM, Weaver DR | title = Targeted disruption of the mPer3 gene: subtle effects on circadian clock function | journal = Molecular and Cellular Biology | volume = 20 | issue = 17 | pages = 6269–75 | date = September 2000 | pmid = 10938103 | doi = 10.1128/MCB.20.17.6269-6275.2000 }}</ref> Per1-/- and Per2-/- animals experience a significant change in free-running period; however, knocking out Per3 in addition to either Per1 or Per2 has little effect on free-running rhythms.<ref name="Bae 2001" /> Furthermore, Per1-/-Per2-/- mice are completely arrhythmic, indicating that these two genes have much more importance to the biological clock than Per3.<ref name="Bae 2001" /> Nonetheless, members of the scientific community have shown that, in human studies, polymorphisms in the gene are strongly related with various aspects of circadian rhythms). |
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Studies show that the Per3 knockout mouse experience a slightly shortened period of locomotor activity (0.5h, <ref name="Shearman 2000" />), and some further suggest that they may be less sensitive to light, in that they entrain more slowly to changes in the light-dark cycle. These studies suggest that PER3 may be involved in the suppression of behavioral activity in response to light, although mPer3 expression is not necessary for circadian rhythms <ref name="van der Veen 2010">{{cite journal| |
Studies show that the Per3 knockout mouse experience a slightly shortened period of locomotor activity (0.5h, <ref name="Shearman 2000" />), and some further suggest that they may be less sensitive to light, in that they entrain more slowly to changes in the light-dark cycle. These studies suggest that PER3 may be involved in the suppression of behavioral activity in response to light, although mPer3 expression is not necessary for circadian rhythms <ref name="van der Veen 2010">{{cite journal | vauthors = van der Veen DR, Archer SN | title = Light-dependent behavioral phenotypes in PER3-deficient mice | journal = Journal of Biological Rhythms | volume = 25 | issue = 1 | pages = 3–8 | date = February 2010 | pmid = 20075295 | doi = 10.1177/0748730409356680 }}</ref><ref name="Pereira 2014">{{cite journal | vauthors = Pereira DS, van der Veen DR, Gonçalves BS, Tufik S, von Schantz M, Archer SN, Pedrazzoli M | title = The effect of different photoperiods in circadian rhythms of per3 knockout mice | journal = BioMed Research International | volume = 2014 | pages = 170795 | date = 2014 | pmid = 24982860 | doi = 10.1155/2014/170795 }}</ref> |
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==Clinical significance== |
==Clinical significance== |
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... |
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* [[PER1]] |
* [[PER1]] |
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* [[PER2]] |
* [[PER2]] |
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==References== |
== References == |
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==Further reading== |
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== External links == |
== External links == |
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{{NLM content}} |
{{NLM content}} |
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{{Transcription factors}} |
{{Transcription factors}} |
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[[Category:Transcription factors]] |
[[Category:Transcription factors]] |
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[[Category:Circadian rhythm]] |
[[Category:Circadian rhythm]] |
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[[Category:PAS-domain-containing proteins]] |
[[Category:PAS-domain-containing proteins]] |
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{{gene-1-stub}} |
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Revision as of 04:07, 12 April 2017
The PER3 gene encodes the period circadian protein homolog 3 protein in humans.[5]
Function
This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression in the suprachiasmatic nucleus continues in constant darkness, and a shift in the light/dark cycle evokes a proportional shift of gene expression in the suprachiasmatic nucleus. The specific function of this gene is not yet known.[6]
Role in chronobiology
The RNA levels of mPer3 oscillate with a circadian rhythm in both the SCN and in the eyes, as well as in peripheral tissues, including the liver, skeletal muscle, and testis.[7] Unlike Per1 and Per2, of which the mRNA is induced in response to light, Per3 mRNA in the SCN does not respond to light. This suggests that Per3 may be regulated differently than either Per1 or Per2.[7]
The mPER3 protein contains a PAS domain, similar to mPER1 and mPER2. Likely, mPER3 binds to other proteins using this domain.[7] However, while PER1/2 have been shown to be important in the transcription-translation feedback loop involved in the intracellular circadian clock, the influence of PER3 in this loop has not yet been fully elucidated, given that mPER3 does not appear to be functionally redundant to mPER1 and mPER2.[8] Researchers hypothesize that mPer3 may not be important to the core clock loop at all.[8]
Misconceptions
While the Per3 gene is a paralog to the Per1 and Per2 genes, studies in animals generally show that it does not contribute significantly to circadian rhythms. Functional Per3-/- animals experience only small changes in free-running period [8],and do not respond significantly differently to light pulses.[9] Per1-/- and Per2-/- animals experience a significant change in free-running period; however, knocking out Per3 in addition to either Per1 or Per2 has little effect on free-running rhythms.[8] Furthermore, Per1-/-Per2-/- mice are completely arrhythmic, indicating that these two genes have much more importance to the biological clock than Per3.[8] Nonetheless, members of the scientific community have shown that, in human studies, polymorphisms in the gene are strongly related with various aspects of circadian rhythms).
Studies show that the Per3 knockout mouse experience a slightly shortened period of locomotor activity (0.5h, [9]), and some further suggest that they may be less sensitive to light, in that they entrain more slowly to changes in the light-dark cycle. These studies suggest that PER3 may be involved in the suppression of behavioral activity in response to light, although mPer3 expression is not necessary for circadian rhythms [10][11]
Clinical significance
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000049246 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028957 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Shearman LP, Zylka MJ, Weaver DR, Kolakowski LF, Reppert SM (December 1997). "Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei". Neuron. 19 (6): 1261–9. doi:10.1016/S0896-6273(00)80417-1. PMID 9427249.
- ^ "Entrez Gene: PER3 period homolog 3 (Drosophila)".
- ^ a b c Zylka MJ, Shearman LP, Weaver DR, Reppert SM (June 1998). "Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain". Neuron. 20 (6): 1103–10. doi:10.1016/S0896-6273(00)80492-4. PMID 9655499.
- ^ a b c d e Bae K, Jin X, Maywood ES, Hastings MH, Reppert SM, Weaver DR (May 2001). "Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock". Neuron. 30 (2): 525–36. doi:10.1016/S0896-6273(01)00302-6. PMID 11395012.
- ^ a b Shearman LP, Jin X, Lee C, Reppert SM, Weaver DR (September 2000). "Targeted disruption of the mPer3 gene: subtle effects on circadian clock function". Molecular and Cellular Biology. 20 (17): 6269–75. doi:10.1128/MCB.20.17.6269-6275.2000. PMID 10938103.
- ^ van der Veen DR, Archer SN (February 2010). "Light-dependent behavioral phenotypes in PER3-deficient mice". Journal of Biological Rhythms. 25 (1): 3–8. doi:10.1177/0748730409356680. PMID 20075295.
- ^ Pereira DS, van der Veen DR, Gonçalves BS, Tufik S, von Schantz M, Archer SN, Pedrazzoli M (2014). "The effect of different photoperiods in circadian rhythms of per3 knockout mice". BioMed Research International. 2014: 170795. doi:10.1155/2014/170795. PMID 24982860.
{{cite journal}}: CS1 maint: unflagged free DOI (link)
External links
- PER3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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