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Phosphorylation and nuclear translocation of the CRY:PER:kinase complex

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9931530

PubChem

R-HSA-9931530

Description

Cryptochrome proteins (CRY1, CRY2) and Period proteins (PER1, PER2, PER3) are translated in the cytosol. CDK5 phosphoryates PER2 in the cytosol and phosphorylated PER2 interacts with CRY1 (inferred from mouse homologs in Brenna et al. 2019). The heterodimer associates with kinases Casein kinase I delta (CSNK1D) and Casein kinase I epsilon (CSNK1E) and other CRY and PER proteins in a large complex in the cytosol (inferred from mouse homologs in Nangle et al. 2014, Aryal et al. 2017) and the CRY and PER proteins are phosphorylated by CSNK1D and CSNK1E (Toh et al. 2001, Camacho et al. 2001, inferred from mouse homologs in Akashi et al. 2002, Eide et al. 2002, reviewed in Hirano et al. 2016, Yang et al. 2017, Ode et al. 2018, Narasimamurthy and Virshup 2021). The large complex containing the phosphorylated CRY and PER proteins is then translocated into the nucleus (inferred from mouse homologs in Kume et al. 1999, Vielhaber et al. 2000, Aryal et al. 2017, Cao et al. 2023), though there is a discrepancy in the measured sizes of the nuclear complex. Cao et al. (2023) used gel exclusion chromatography and glycerol gradient centrifugation and found a mass of 707 kDa: Aryal et al. (2017) used a novel electrophoretic method and found a mass of 1.9 MDa. The large CRY:PER:kinase complex then associates with phosphorylated BMAL1:CLOCK heterodimers (and likely with BMAL1:NPAS2 heterodimers) and represses the transactivation activity of BMAL1:CLOCK (inferred from mouse homologs in Griffin et al. 1999, Ye et al. 2014, Chiou et al. 2016, Cao et al. 2021).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 9** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O15055	Period circadian protein homolog 2	KIAA0347 PER2	view
O15534	Period circadian protein homolog 1	KIAA0482 PER PER1 RIGUI	view
P19784	Casein kinase II subunit alpha'	CK2A2 CSNK2A2	view
P36873	Serine/threonine-protein phosphatase PP1-gamma catalytic subunit	PPP1CC	view
P56645	Period circadian protein homolog 3	GIG13 PER3	view
P62136	Serine/threonine-protein phosphatase PP1-alpha catalytic subunit	PPP1A PPP1CA	view
P62140	Serine/threonine-protein phosphatase PP1-beta catalytic subunit	PPP1CB	view
P68400	Casein kinase II subunit alpha	CK2A1 CSNK2A1	view
Q00535	Cyclin-dependent kinase 5	CDK5 CDKN5 PSSALRE	view

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