BioPAX pathway converted from "CSNK1E,CSNK1D phosphorylate CRY and PER proteins" in the Reactome database. 2.7.11.1 CSNK1E,CSNK1D phosphorylate CRY and PER proteins CSNK1E,CSNK1D phosphorylate CRY and PER proteins 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.<br>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.<br>A mutation at Serine662 of PER2 is responsible for familial advanced phase sleep syndrome, however the particular kinase responsible for phosphorylating Serine662 is unknown. Authored: May, B, 2009-05-17 22:04:50 Reviewed: D'Eustachio, P, 2009-05-26 22:13:22 Reviewed: Albrecht, Urs, 2010-06-23 Reviewed: Kay, SA, 2010-06-23 Reviewed: Hirota, T, 2010-06-23 Reviewed: Delaunay, F, 2010-06-23 Edited: May, B, 2009-06-02 00:51:49 Reactome DB_ID: 113592 2 cytosol GO 0005829 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP Reactome http://www.reactome.org ChEBI 30616 Reactome DB_ID: 421287 1 CRY:PER:Kinase [cytosol] CRY:PER:Kinase Converted from EntitySet in Reactome Reactome DB_ID: 421289 1 CSNK1E,CSNK1D [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CSNK1E [cytosol] Homo sapiens NCBI Taxonomy 9606 UniProt P49674 Converted from EntitySet in Reactome Reactome DB_ID: 400223 1 CRY1,2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CRY2 [cytosol] CRY1 [cytosol] UniProt Q49AN0 UniProt Q16526 Converted from EntitySet in Reactome Reactome DB_ID: 400344 1 PER1,PER2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PER2 [cytosol] PER1 [cytosol] UniProt O15055 UniProt O15534 Reactome Database ID Release 82 421287 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421287 Reactome R-HSA-421287 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-421287.2 Reactome DB_ID: 421296 1 p-CRY:p-PER:Kinase [cytosol] p-CRY:p-PER:Kinase Converted from EntitySet in Reactome Reactome DB_ID: 400287 1 p-CRY1,p-CRY2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity p-S-CRY1 [cytosol] p-S-CRY2 [cytosol] Converted from EntitySet in Reactome Reactome DB_ID: 421289 1 Converted from EntitySet in Reactome Reactome DB_ID: 400346 1 p-PER1,p-PER2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity p-S-PER1 [cytosol] p-S-PER2 [cytosol] Reactome Database ID Release 82 421296 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421296 Reactome R-HSA-421296 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-421296.2 Reactome DB_ID: 29370 2 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 421287 GO 0004674 GO molecular function Reactome Database ID Release 82 421295 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421295 Reactome Database ID Release 82 400382 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400382 Reactome R-HSA-400382 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400382.4 15800623 Pubmed 2005 Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome Xu, Y Padiath, QS Shapiro, RE Jones, CR Wu, SC Saigoh, N Saigoh, K Ptácek, LJ Fu, YH Nature 434:640-4 15917222 Pubmed 2005 SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein Shirogane, T Jin, J Ang, XL Harper, JW J Biol Chem 280:26863-72 14750904 Pubmed 2004 Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts Miyazaki, K Nagase, T Mesaki, M Narukawa, J Ohara, O Ishida, N Biochem J 380:95-103 11165242 Pubmed 2001 Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2 Camacho, F Cilio, M Guo, Y Virshup, DM Patel, K Khorkova, O Styren, S Morse, B Yao, Z Keesler, GA FEBS Lett 489:159-65 10790862 Pubmed 2000 Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon Keesler, GA Camacho, F Guo, Y Virshup, D Mondadori, C Yao, Z Neuroreport 11:951-5 17218255 Pubmed 2007 Modeling of a human circadian mutation yields insights into clock regulation by PER2 Xu, Y Toh, KL Jones, CR Shin, JY Fu, YH Ptácek, LJ Cell 128:59-70 11232563 Pubmed 2001 An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome Toh, KL Jones, CR He, Y Eide, EJ Hinz, WA Virshup, DM Ptácek, LJ Fu, YH Science 291:1040-3 19805222 Pubmed 2009 CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock Isojima, Y Nakajima, M Ukai, H Fujishima, H Yamada, RG Masumoto, KH Kiuchi, R Ishida, M Ukai-Tadenuma, M Minami, Y Kito, R Nakao, K Kishimoto, W Yoo, SH Shimomura, K Takao, T Takano, A Kojima, T Nagai, K Sakaki, Y Takahashi, JS Ueda, HR Proc Natl Acad Sci U S A 106:15744-9 INHIBITION Reactome Database ID Release 82 5656529 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5656529 Reactome R-HSA-5656529 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5656529.1 Converted from EntitySet in Reactome Reactome DB_ID: 163538 PP1 catalytic subunit [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PPP1CB [cytosol] PPP1CA [cytosol] PPP1CC [cytosol] UniProt P62140 UniProt P62136 UniProt P36873