period circadian protein homolog 2; hPER2; circadian clock protein PERIOD 2 (PER2, KIAA0347)
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Function
- component of the circadian clock mechanism which is essential for generating circadian rhythms
- negative element in the circadian transcriptional loop
- influences clock function by interacting with other circadian regulatory proteins & transporting them to the nucleus
- negatively regulates CLOCK|NPAS2-BMAL1|BMAL2-induced transactivation (putative)
- phosphorylated by CSNK1E & CSNK1D
- phosphorylation results in PER2 protein degradation
- homodimer
- component of the circadian core oscillator
- interacts with NFIL3 (putative)
Structure
- contains 1 PAC (PAS-associated C-terminal) domain
- contains 2 PAS (PER-ARNT-SIM) domains
Compartment
- nucleus (putative), cytoplasm
- mainly nuclear
- nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins &/or by phosphorylation
- retention of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer formation or by interaction with CSNK1E &/or phosphorylation which appears to mask the PER nuclear localization signal
- translocated to the nucleus by CRY1 or CRY2 (putative)
Alternative splicing
named isoforms=2
Expression
- widely expressed
- found in heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
- high levels in skeletal muscle & pancreas
- low level in lung
- serum-induced levels in fibroblasts show circadian oscillations
- maximum levels after 1 hour stimulation, minimum levels after 12 hours
- another peak is then observed after 24 hours
Pathology
- defects in PER2 are a cause of advanced sleep-phase syndrome