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period circadian protein homolog 1; hPER1; circadian clock protein PERIOD 1; circadian pacemaker protein Rigui (PER1, KIAA0482, PER, RIGUI)
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 on Ser by CSNK1E
- also can be phosphorylated by the delta isoform
- phosphorylation by CSNK1 retains PER1 in the cytoplasm & leads to its ubiquitination & subsequent degradation
- phosphorylated upon DNA damage, probably by ATM or ATR
- ubiquitinated (putative)
- component of the circadian core oscillator
- interacts directly with TIMELESS, PER2, PER3 &, through a C-terminal domain, with CRY1 & CRY2
- interaction with CSNK1D or CSNK1E promotes nuclear location of PER proteins
- interacts with GPRASP1 (putative)
- binding to CSNK1G2 triggers proteasomal degradation
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 PER1 nuclear localization signal
- translocated to the nucleus by CRY1 or CRY2 (putative)
Alternative splicing:
- named isoforms=3
- additional isoforms seem to exist
Expression:
- widely expressed
- found in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, kidney, spleen, thymus, prostate, testis, ovary & small intestine
- highest level in skeletal muscle
- low level in kidney
- 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 20 hours
- protein levels show maximum levels at 6 hours, decrease to reach minimum levels at 20 hours, & increase again to reach a second peak after 26 hours. Levels then decrease slightly & then increase to maximum levels at 32 hours
- levels of phosphorylated form increase between 3 hours & 12 hours
General
period circadian protein (hPER)
phosphoprotein
Properties
SIZE: entity length = 1290 aa
MW = 136 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: serine-rich region {49-129}
MOTIF: serine residue (SEVERAL)
PAS domain {208-275}
PAS domain {348-414}
PAC domain {422-465}
nuclear export signal {486-498}
CSNK1E binding domain {596-815}
MOTIF: serine-rich region {653-656}
MOTIF: serine residue (SEVERAL)
Ser phosphorylation site {S704}
Ser phosphorylation site {S815}
nuclear translocation signal {827-843}
proline-rich region
SITE: 848-1013
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S979}
Ser phosphorylation site {S980}
serine-rich region {1030-1104}
MOTIF: serine residue (SEVERAL)
Ser phosphorylation site {S1100}
Ser phosphorylation site {S1103}
Ser phosphorylation site {S1104}
CRY binding domain {1149-1290}
MOTIF: Ser phosphorylation site {S1262}
Ser phosphorylation site {S1263}
glutamate-rich region {1269-1273}
MOTIF: glutamate residue (SEVERAL)
serine-rich region {1276-1279}
MOTIF: serine residue (SEVERAL)
Database Correlations
OMIM 602260
UniProt O15534
PFAM correlations
Entrez Gene 5187
Kegg hsa:5187
References
- UniProt :accession O15534
- Entrez Gene :accession 5187