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

More general terms

• period circadian protein (hPER)
• phosphoprotein

Component of

• circadian core oscillator

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5187
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5187
• OMIM: https://mirror.omim.org/entry/602260
• UniProt: http://www.uniprot.org/uniprot/O15534.html