The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex

A complex containing Cryptochrome proteins CRY1, CRY2, Period proteins PER1, PER2, PER3, and kinases CSNK1D and/or CSNK1E binds a heterodimer containing phosphorylated CLOCK and phosphorylated, acetylated BMAL1 bound to E-boxes in the promoters of target genes (inferred from mouse homologs in Griffin et al. 1999, Langmesser et al. 2008, Ye et al. 2011, Ye et al. 2014, Aryal et al. 2017, Cao et al. 2021). This effectively delivers the kinases CSNK1D and/or CSNK1E to the proximity of CLOCK, resulting in further phosphorylation of CLOCK (inferred from mouse homologs in Cao et al. 2021). NPAS2, which acts redundantly with CLOCK, may be similarly phosphorylated. The phosphorylation of CLOCK causes the dissociation of the BMAL1:CLOCK heterodimer from DNA (inferred from mouse homologs in Ye et al. 2014, Chiou et al. 2016, Cao et al. 2021), terminating the diurnal activation of gene expression by BMAL1:CLOCK.

Summary from Reactome (R-HSA-9931521), read 2026-09-23.