PER2
PER2 is a protein in mammals encoded by the PER2 gene. PER2 is noted for its major role in circadian rhythms.[5][6]
Discovery
The per gene was first discovered using forward genetics in Later experiments in also identified Per2 in humans.
Function
PER2 is a member of the Period family of genes and is expressed in a
PER2 contains
PER2 expression in mice is increased by exposure to 13000 lumens of intense daylight such as
Per2 knockout mice experience a free-running period of around 21.8 hours, compared to the normal mouse free-running period of 23.3 hours. Some of the Per2 knockout mice can also become arrhythmic under constant light conditions. PER2 has also been shown to be possibly important in the development of cancer. PER2 expression is significantly lower in human patients with lymphoma and acute myeloid leukemia.[15]
The PER2 protein seems to be important for the proliferation of
Main interactions
In mammals, mPER2 forms a heterodimer with
Interactions with CK1e
PER2 has been shown to interact with a kinase called CK1e. CK1e phosphorylates PER2 in mammals. In Syrian hamster, a mutation called tau has been discovered in the CK1e, which increases phosphorylation of homologous PER2 leading to a faster degradation and a shortened period.[20] Mutations in hPER2 can cause FASPS because of a lack of phosphorylation site in the mutated hPER2 protein.
Interaction table
| Peak of mRNA | Peak of Protein | Protein Motifs | PER1, PER3 | PER1, CRY1, CRY2 | PER2 binding to Clock/Bmal1 | CK1E | |
|---|---|---|---|---|---|---|---|
| PER2 | ZT 6 | ZT 12 | PAS domain | Binds together through
PAS domain |
Forms heterodimer to
inhibit Clock/Bmal1 |
PER2 inhibits its own transcription
through inhibition of Clock/Bmal1. |
Phosphorylates PER2 |
Clinical significance
A genetic test from a cheek swab can use PER2 expression levels to tell whether a person is an early morning person or a "night owl".[21]
Familial Advanced Sleep Phase
Familial advanced sleep phase (FASP) is characterized as a short period (e.g. 23.3 vs 24.3hr for population) in humans. A mutation in hPER2 decreases its phosphorylation by CK1d, which causes the phenotype seen in some FASP.[22] The primary cause of these FASP is a mutation that changes amino acid 662 from serine to glycine (S662G) in PER2. The S662G mutation makes PER2 mutant protein a stronger repressor than normal PER2, decreasing cellular PER2 levels and therefore causing this form of FASP. The mutation also seems to cause an increase in the turnover rate of PER2 in the nucleus.[16]
Gene
The PER2 gene is located on the long (q) arm of chromosome 2 at position 37.3 and has 25 exons.[9]
Predicted human PER2 protein created from the PER2 gene shares 44% identity with human PER1 and 77% identity with mouse Per2. Northern blots analysis revealed that PER2 was expressed as a 7-kb mRNA in all tissues examined. An additional 1.8-kb transcript was also detected in some tissues.[23] PER2 mRNA has been shown to peak at ZT 6 in the SCN.[16]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000132326 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055866 – 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.
- S2CID 10059149.
- PMID 17218255.
- PMID 23604473.
- S2CID 10059149.
- ^ a b "Entrez Gene: PER2 period homolog 2 (Drosophila)".
- PMID 17971899.
- PMID 25550826.
- PMID 19805059.
- PMID 22504483.
- Christine Hsu (April 27, 2012). "Sunlight May Protect against Heart Attacks and Speed Heart Recovery". Medical Daily.
- PMID 23593233.
- PMID 16987893.
- ^ PMID 18802415.
- PMID 10531061.
- PMID 11533252.
- S2CID 4430366.
- PMID 24904820.
- ^ Roger Highfield (2008-06-06). "Swab test to tell if you're a late sleeper or early riser". Telegraph. Archived from the original on August 12, 2009. Retrieved 2008-06-07.
- S2CID 1848310.
- ^ "OMIM Entry - * 603426 - PERIOD, DROSOPHILA, HOMOLOG OF, 2; PER2". www.omim.org. Retrieved 2015-04-20.
Further reading
- Tafti M, Maret S, Dauvilliers Y (2005). "Genes for normal sleep and sleep disorders". Annals of Medicine. 37 (8): 580–9. S2CID 5756695.
External links
- PER2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: O15055 (Human Period circadian protein homolog 2) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: O54943 (Mouse Period circadian protein homolog 2) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.