CSNK1E,CSNK1D phosphorylate CRY and PER proteins

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
In the cytosol the kinases CSNK1D (casein kinase I delta) and CSNK1E (casein kinase I epsilon) phosphorylate PER1, PER2, CRY1, and CRY2 at multiple sites. Evidence indicates that PER:CRY complexes form a stable ternary complex with either CSNK1E or CSNK1D. Both kinases are able to bind and phosphorylate PER proteins. CSNK1E has been shown to phosphorylate CRY proteins only when they are complexed with PER proteins.
PER proteins contain a nuclear localization sequence and a nuclear export sequence allowing their movement into and out of the nucleus. Phosphorylation is required for transit of PER:CRY:kinase complexes into the nucleus and for interaction of PER proteins with the ubiquitin-mediated degradation process in the cytoplasm.
A mutation at Serine662 of PER2 is responsible for familial advanced phase sleep syndrome, however the particular kinase responsible for phosphorylating Serine662 is unknown.
Literature References
PubMed ID Title Journal Year
10790862 Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon

Virshup, D, Yao, Z, Mondadori, C, Camacho, F, Keesler, GA, Guo, Y

Neuroreport 2000
15917222 SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein

Shirogane, T, Ang, XL, Jin, J, Harper, JW

J Biol Chem 2005
11232563 An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome

Eide, EJ, Jones, CR, Virshup, DM, Ptácek, LJ, He, Y, Toh, KL, Hinz, WA, Fu, YH

Science 2001
15800623 Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome

Jones, CR, Saigoh, K, Ptácek, LJ, Wu, SC, Xu, Y, Saigoh, N, Shapiro, RE, Fu, YH, Padiath, QS

Nature 2005
11165242 Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2

Styren, S, Yao, Z, Khorkova, O, Morse, B, Cilio, M, Virshup, DM, Camacho, F, Keesler, GA, Guo, Y, Patel, K

FEBS Lett 2001
17218255 Modeling of a human circadian mutation yields insights into clock regulation by PER2

Jones, CR, Ptácek, LJ, Shin, JY, Toh, KL, Xu, Y, Fu, YH

Cell 2007
19805222 CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock

Nakao, K, Minami, Y, Ukai, H, Takao, T, Shimomura, K, Masumoto, KH, Kiuchi, R, Ukai-Tadenuma, M, Yamada, RG, Sakaki, Y, Takano, A, Nagai, K, Nakajima, M, Yoo, SH, Isojima, Y, Ueda, HR, Fujishima, H, Kojima, T, Kito, R, Kishimoto, W, Takahashi, JS, Ishida, M

Proc Natl Acad Sci U S A 2009
14750904 Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts

Ishida, N, Nagase, T, Ohara, O, Miyazaki, K, Narukawa, J, Mesaki, M

Biochem J 2004
Catalyst Activity

protein serine/threonine kinase activity of CRY:PER:Kinase [cytosol]

This event is regulated
Inferred From
Cite Us!