period circadian protein homolog 2; hPER2; circadian clock protein PERIOD 2 (PER2, KIAA0347)

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 directly with PER1 & PER3, & through a C-terminal domain, with CRY1 & CRY2 - interaction with CSNK1D or CSNK1E promotes nuclear location of PER proteins - interacts, via its second PAS domain, with TIMELESS in vitro - 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

General

period circadian protein (hPER) phosphoprotein

Properties

SIZE: entity length = 1255 aa MW = 137 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: PAS domain {181-248} PAS domain {321-387} PAC domain {395-438} nuclear export signal {459-471} arginine-rich region {510-513} MOTIF: arginine residue (SEVERAL) Ser phosphorylation site {S527} Ser phosphorylation site {S530} Ser phosphorylation site {S533} Ser phosphorylation site {S540} CSNK1E binding domain {557-771} MOTIF: Ser phosphorylation site {S662} Ser phosphorylation site {S696} Ser phosphorylation site {S700} Ser phosphorylation site {S714} Ser phosphorylation site {S766} Ser phosphorylation site {S771} nuclear translocation signal {789-805} proline-rich region SITE: 842-979 MOTIF: proline residue (SEVERAL) Thr phosphorylation site {T864} Ser phosphorylation site {S945} Ser phosphorylation site {S977} Ser phosphorylation site {S1124} CRY binding domain {1155-1255}

Database Correlations

OMIM correlations MORBIDMAP 603426 UniProt O15055 PFAM correlations Entrez Gene 8864 Kegg hsa:8864