BioPAX pathway converted from "Cyclin A/B1/B2 associated events during G2/M transition" in the Reactome database.Cyclin A/B1/B2 associated events during G2/M transitionCyclin A/B1/B2 associated events during G2/M transitionThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Formation of Cyclin A:Cdc2 complexesFormation of Cyclin A:Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 103201331cytosolGO0005829CCNA [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactomehttp://www.reactome.orgReactome DB_ID: 103201041UniProt:F7E741Xenopus tropicalisNCBI Taxonomy8364UniProtF7E741Chain Coordinates1EQUAL297EQUALReactome DB_ID: 103201351CCNA:CDK1 [cytosol]CCNA:CDK1Converted from EntitySet in ReactomeReactome DB_ID: 103201331Reactome DB_ID: 1032010411EQUAL297EQUALReactome Database ID Release 7510320135Database 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=10320135ReactomeR-XTR-1700911Reactome 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-XTR-170091.1Reactome Database ID Release 7510320137Database 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=10320137ReactomeR-XTR-1700841Reactome 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-XTR-170084.1Cyclin A is synthesized and associates with Cdc2 in G1. Cyclin dependent kinases are themselves catalytically inactive due to the fact that their active sites are blocked by a portion of the CDK molecule itself. Binding to their corresponding cyclin partner results in a conformational change that partially exposes the active site.1717476Pubmed1991Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transportPines, JHunter, TonyJ Cell Biol 115:1-179001210Pubmed1997The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex.Liu, FStanton, JJWu, ZPiwnica-Worms, HMol Cell Biol 17:571-83inferred by electronic annotationIEAGOIEATranslocation of Cyclin A:phospho-Cdc2 (Thr 14) to the nucleusTranslocation of Cyclin A:phospho-Cdc2 (Thr 14) to the nucleusThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103201451CCNA:p-T14-CDK1 [cytosol]CCNA:p-T14-CDK1Converted from EntitySet in ReactomeReactome DB_ID: 103201331Reactome DB_ID: 103200551O-phospho-L-threonine at 14 (in Homo sapiens)14EQUALO-phospho-L-threonine [MOD:00047]1EQUAL297EQUALReactome Database ID Release 7510320145Database 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=10320145ReactomeR-XTR-1700851Reactome 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-XTR-170085.1Reactome DB_ID: 103201391nucleoplasmGO0005654CCNA:p-T14-CDK1 [nucleoplasm]CCNA:p-T14-CDK1Reactome DB_ID: 103200801O-phospho-L-threonine at 14 (in Homo sapiens)14EQUAL1EQUAL297EQUALConverted from EntitySet in ReactomeReactome DB_ID: 103070491CCNA [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 7510320139Database 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=10320139ReactomeR-XTR-1700901Reactome 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-XTR-170090.1Reactome Database ID Release 7510320147Database 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=10320147ReactomeR-XTR-1700881Reactome 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-XTR-170088.1Cyclin A:Cdc2 complexes translocate to the nucleus in G1 and may associate with condensing chromosomes in prophase (Pines and Hunter 1991).inferred by electronic annotationIEAGOIEA2.7.11CAK-mediated phosphorylation of Cyclin A:Cdc2 complexesCAK-mediated phosphorylation of Cyclin A:Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103201391Reactome DB_ID: 293581ATP(4-) [ChEBI:30616]ATP(4-)Adenosine 5'-triphosphateatpATPChEBI30616Reactome DB_ID: 103201411CCNA:p-T14,T161-CDK1 [nucleoplasm]CCNA:p-T14,T161-CDK1Converted from EntitySet in ReactomeReactome DB_ID: 103070491Reactome DB_ID: 103201171O-phospho-L-threonine at 14 (in Homo sapiens)14EQUALO-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome Database ID Release 7510320141Database 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=10320141ReactomeR-XTR-1700921Reactome 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-XTR-170092.1Reactome DB_ID: 1135821ADP(3-) [ChEBI:456216]ADP(3-)ADP trianion5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADPChEBI456216PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10311012CAK [nucleoplasm]CAKReactome DB_ID: 103110021UniProt:Q28II8cdk7UniProtQ28II81EQUAL346EQUALReactome DB_ID: 103110061UniProt:F7A4I0UniProtF7A4I01EQUAL323EQUALReactome DB_ID: 103110101UniProt:F6Y1E8cyb561d1UniProtF6Y1E81EQUAL309EQUALReactome Database ID Release 7510311012Database 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=10311012ReactomeR-XTR-692211Reactome 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-XTR-69221.1GO0004674GO molecular functionReactome Database ID Release 7510320125Database 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=10320125Reactome Database ID Release 7510320143Database 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=10320143ReactomeR-XTR-1700871Reactome 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-XTR-170087.1Full activity of most CDKs is dependent on CAK mediated phosphorylation at a conserved residue (Thr 161 in Cdc2). This modification is thought to improve substrate binding. High affinity binding of Cyclin A within the Cyclin A:Cdc2 complex requires this phosphorylation (Desai et al 1995).7799941Pubmed1995Effects of phosphorylation by CAK on cyclin binding by CDC2 and CDK2.Desai, DWessling, HCFisher, RPMorgan, DOMol Cell Biol 15:345-50inferred by electronic annotationIEAGOIEATranslocation of active Cdc25C to the nucleusTranslocation of active Cdc25C to the nucleusThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103162681UniProt:F7B6Y3cntn1UniProtF7B6Y3O-phospho-L-serine at 198 (in Homo sapiens)198EQUALO-phospho-L-serine [MOD:00046]1EQUAL473EQUALReactome DB_ID: 103201661O-phospho-L-serine at 198 (in Homo sapiens)198EQUAL1EQUAL473EQUALReactome Database ID Release 7510320168Database 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=10320168ReactomeR-XTR-1701491Reactome 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-XTR-170149.1During interphase, CDC25C, phosphorylated on serine residue 216, is associated with 14-3-3 proteins, preventing nuclear import. At the onset of mitosis, dephosphorylation of S216 of Cdc25C and dissociation of 14-3-3, with phosphorylation of CDC25C on S198 by activated PLK1 promotes nuclear import (Takizawa and Morgan 2000, Toyoshima-Morimoto et al. 2002, Bonnet et al. 2008). Activating CDC25C phosphorylation and nuclear translocation may further be enhanced by activated CCNB:CDK1 complexes (Bonnet et al. 2008).18384749Pubmed2008Differential phosphorylation of Cdc25C phosphatase in mitosisBonnet, JérômeMayonove, PaulineMorris, May CBiochem. Biophys. Res. Commun. 370:483-811063929Pubmed2000Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25CTakizawa, CGMorgan, DOCurr Opin Cell Biol 12:658-6511897663Pubmed2002Plk1 promotes nuclear translocation of human Cdc25C during prophaseToyoshima-Morimoto, FTaniguchi, ENishida, EEMBO Rep 3:341-8inferred by electronic annotationIEAGOIEA3.1.3.16Dephosphorylation of nuclear Cyclin A:phospho-Cdc2 complexesDephosphorylation of nuclear Cyclin A:phospho-Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 1135182water [ChEBI:15377]waterChEBI15377Reactome DB_ID: 103201771CCNA:p-T14,Y15,T161-CDK1 [nucleoplasm]CCNA:p-T14,Y15,T161-CDK1Reactome DB_ID: 103200841O-phospho-L-threonine at 161 (in Homo sapiens)161EQUALO-phospho-L-threonine at 14 (in Homo sapiens)14EQUALO4'-phospho-L-tyrosine at 15 (in Homo sapiens)15EQUALO4'-phospho-L-tyrosine [MOD:00048]1EQUAL297EQUALConverted from EntitySet in ReactomeReactome DB_ID: 103070491Reactome Database ID Release 7510320177Database 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=10320177ReactomeR-XTR-1701471Reactome 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-XTR-170147.1Reactome DB_ID: 103201791CCNA:p-T161-CDK1 [nucleoplasm]CCNA:p-T161-CDK1Converted from EntitySet in ReactomeReactome DB_ID: 103070491Reactome DB_ID: 103200901O-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome Database ID Release 7510320179Database 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=10320179ReactomeR-XTR-1701461Reactome 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-XTR-170146.1Reactome DB_ID: 1135502hydrogenphosphate [ChEBI:43474]hydrogenphosphate[PO3(OH)](2-)HYDROGENPHOSPHATE IONhydrogen phosphate[P(OH)O3](2-)HPO4(2-)phosphateINORGANIC PHOSPHATE GROUPChEBI43474PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10307366UniProt:Q28DL0cdc25aUniProtQ28DL01EQUAL524EQUALGO0004721GO molecular functionReactome Database ID Release 7510307367Database 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=10307367Reactome Database ID Release 7510320181Database 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=10320181ReactomeR-XTR-1701581Reactome 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-XTR-170158.1Activation of the cyclin A:Cdc2 complexes at mitosis requires the removal of the inhibitory phosphate groups on Cdc2 (CDK1). This dephosphorylation is achieved by the activity of the CDC25A phosphatase (Timofeev et al. 2009). CDC25A, CDC25B, and CDC25C are kept inactive during interphase and are activated at the G2/M transition (see Wolfe and Gould 2004).15107615Pubmed2004Inactivating Cdc25, mitotic styleWolfe, BAGould, KLCell Cycle 3:601-319192479Pubmed2009Human Cdc25A phosphatase has a non-redundant function in G2 phase by activating Cyclin A-dependent kinasesTimofeev, OlegCizmecioglu, OnurHu, EntanOrlik, ThomasHoffmann, IngridFEBS Lett. 583:841-7inferred by electronic annotationIEAGOIEAFormation of Cyclin B:Cdc2 complexesFormation of Cyclin B:Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 103201021CCNB [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityccnb2 [cytosol]ccnb1.2 [cytosol]UniProtF6QGW4UniProtF6QF79Reactome DB_ID: 1032010411EQUAL297EQUALReactome DB_ID: 103201061CCNB:CDK1 [cytosol]CCNB:CDK1Converted from EntitySet in ReactomeReactome DB_ID: 103201021Reactome DB_ID: 1032010411EQUAL297EQUALReactome Database ID Release 7510320106Database 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=10320106ReactomeR-XTR-1700771Reactome 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-XTR-170077.1Reactome Database ID Release 7510320115Database 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=10320115ReactomeR-XTR-1700571Reactome 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-XTR-170057.1Cyclin dependent kinases are themselves catalytically inactive due to the fact that their active site is blocked by a portion of the Cdk molecule itself. Binding to their corresponding cyclin partner results in conformational change that partially exposes the active site. The two B-type cyclins localize to different regions within the cell and and are thought to have specific roles as CDK1-activating subunits (see Bellanger et al., 2007). Cyclin B1 is primarily cytoplasmic during interphase and translocates into the nucleus at the onset of mitosis (Jackman et al., 1995; Hagting et al., 1999). Cyclin B2 colocalizes with the Golgi apparatus and contributes to its fragmentation during mitosis (Jackman et al., 1995; Draviam et al., 2001).17533373Pubmed2007Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2Bellanger, Sde Gramont, ASobczak-Thépot, JOncogene 26:7175-8410395539Pubmed1999Translocation of cyclin B1 to the nucleus at prophase requires a phosphorylation-dependent nuclear import signalHagting, AJackman, MSimpson, KPines, JCurr Biol 9:680-911238451Pubmed2001The localization of human cyclins B1 and B2 determines CDK1 substrate specificity and neither enzyme requires MEK to disassemble the Golgi apparatusDraviam, VMOrrechia, SLowe, MPardi, RPines, JJ Cell Biol 152:945-587737117Pubmed1995Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatusJackman, MFirth, MPines, JEMBO J 14:1646-54inferred by electronic annotationIEAGOIEA2.7.11Myt-1 mediated phosphorylation of Cyclin B:Cdc2 complexesMyt-1 mediated phosphorylation of Cyclin B:Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103201061Reactome DB_ID: 1135921Reactome DB_ID: 293701Reactome DB_ID: 103201081CCNB:p-T14-CDK1 [cytosol]CCNB:p-T14-CDK1Converted from EntitySet in ReactomeReactome DB_ID: 103201021Reactome DB_ID: 103200551O-phospho-L-threonine at 14 (in Homo sapiens)14EQUAL1EQUAL297EQUALReactome Database ID Release 7510320108Database 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=10320108ReactomeR-XTR-1700691Reactome 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-XTR-170069.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10320110UniProt:F6V613pkmyt1UniProtF6V6131EQUAL499EQUALReactome Database ID Release 7510320111Database 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=10320111Reactome Database ID Release 7510320113Database 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=10320113ReactomeR-XTR-1700551Reactome 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-XTR-170055.1Myt1, which localizes preferentially to the endoplasmic reticulum and Golgi complex, phosphorylates Cdc2 on threonine 14 ( Liu et al., 1997).9268380Pubmed1997Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activityBooher, RNHolman, PSFattaey, AJ Biol Chem 272:22300-6inferred by electronic annotationIEAGOIEATranslocation of Cyclin B1:phospho-Cdc2 complexes to the nucleusTranslocation of Cyclin B1:phospho-Cdc2 complexes to the nucleusThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 103200761cytoplasmic Cyclin B1:Cdc2 complexes [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 103200941nuclear Cyclin B1:Cdc2 complexes [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 7510320096Database 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=10320096ReactomeR-XTR-1700441Reactome 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-XTR-170044.1During interphase, cyclin B1:Cdc2 shuttles continuously in and out of the nucleus. Cyclin B1:Cdc2 is transported into the nucleus by an unusual mechanism that requires importin b but not importin a or Ran. Dissociation of the cyclin-B1:Cdc2:importin complex in the nucleus requires ATP and involves other yet unidentified nuclear factors (Takizawa et al.,1991).9670027Pubmed1998MPF localization is controlled by nuclear exportHagting, AKarlsson, CClute, PJackman, MPines, JEMBO J 17:4127-3810393926Pubmed1999Ran-independent nuclear import of cyclin B1-Cdc2 by importin betaTakizawa, CGWeis, KMorgan, DOProc Natl Acad Sci U S A 96:7938-439679058Pubmed1998Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1Yang, JBardes, ESMoore, JDBrennan, JPowers, MAKornbluth, SGenes Dev 12:2131-43inferred by electronic annotationIEAGOIEA2.7.11CAK-mediated phosphorylation of Cyclin B1:Cdc2 complexesCAK-mediated phosphorylation of Cyclin B1:Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103200821CCNB1:p-T14-CDK1 [nucleoplasm]CCNB1:p-T14-CDK1Reactome DB_ID: 103200801O-phospho-L-threonine at 14 (in Homo sapiens)14EQUAL1EQUAL297EQUALReactome DB_ID: 103200781UniProt:F6QF79ccnb1.21EQUAL433EQUALReactome Database ID Release 7510320082Database 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=10320082ReactomeR-XTR-1700561Reactome 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-XTR-170056.1Reactome DB_ID: 293581Reactome DB_ID: 103201191CCNB1:p-T14,T161-CDK1 [nucleoplasm]CCNB1:p-T14,T161-CDK1Reactome DB_ID: 103201171O-phospho-L-threonine at 14 (in Homo sapiens)14EQUALO-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome DB_ID: 1032007811EQUAL433EQUALReactome Database ID Release 7510320119Database 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=10320119ReactomeR-XTR-1700731Reactome 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-XTR-170073.1Reactome DB_ID: 1135821PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10311012Reactome Database ID Release 7510320127Database 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=10320127ReactomeR-XTR-1700761Reactome 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-XTR-170076.1Full activity of most CDKs is dependent on CAK mediated phosphorylation at a conserved residue (Thr161 in Cdc2). This modification is thought to improve substrate binding. Cyclin B:Cdc2 complexes have considerably low activity in the absence of CAK mediated phosphorylation (Desai et al 1995).inferred by electronic annotationIEAGOIEATranslocation of Cyclin B1:phospho-Cdc2 to the cytoplasmTranslocation of Cyclin B1:phospho-Cdc2 to the cytoplasmThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103200861CCNB1:p-T14,Y15,T161-CDK1 [nucleoplasm]CCNB1:p-T14,Y15,T161-CDK1Reactome DB_ID: 103200841O-phospho-L-threonine at 161 (in Homo sapiens)161EQUALO-phospho-L-threonine at 14 (in Homo sapiens)14EQUALO4'-phospho-L-tyrosine at 15 (in Homo sapiens)15EQUAL1EQUAL297EQUALReactome DB_ID: 1032007811EQUAL433EQUALReactome Database ID Release 7510320086Database 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=10320086ReactomeR-XTR-1700651Reactome 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-XTR-170065.1Reactome DB_ID: 103200661CCNB1:p-T14,Y15,T161-CDK1 [cytosol]CCNB1:p-T14,Y15,T161-CDK1Reactome DB_ID: 103200641O-phospho-L-threonine at 161 (in Homo sapiens)161EQUALO-phospho-L-threonine at 14 (in Homo sapiens)14EQUALO4'-phospho-L-tyrosine at 15 (in Homo sapiens)15EQUAL1EQUAL297EQUALReactome DB_ID: 1032005911EQUAL433EQUALReactome Database ID Release 7510320066Database 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=10320066ReactomeR-XTR-1700681Reactome 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-XTR-170068.1Reactome Database ID Release 7510320123Database 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=10320123ReactomeR-XTR-1700721Reactome 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-XTR-170072.1During interphase, cyclin B1 shuttles continuously in and out of the nucleus. The cyclin B cytoplasmic retention sequence (CRS), which is responsible for its interphase cytoplasmic localization, functions as a nuclear export sequence (Yang et al., 1998).inferred by electronic annotationIEAGOIEAACTIVATIONReactome Database ID Release 7510320124Database 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=10320124Reactome DB_ID: 10320121UniProt:F7EP94acad8UniProtF7EP941EQUAL1071EQUALTranslocation of Cdc25B to the cytoplasmTranslocation of Cdc25B to the cytoplasmThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103201511UniProt:F7A6V5cdc25bUniProtF7A6V51EQUAL580EQUALReactome DB_ID: 1032015311EQUAL580EQUALReactome Database ID Release 7510320155Database 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=10320155ReactomeR-XTR-1701201Reactome 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-XTR-170120.1Cdc25B shuttles between the nucleus and the cytoplasm. Translocation out of the nucleus involves a nuclear export sequence in the N-terminus of Cdc25B (Lindqvist et al., 2004).15456846Pubmed2004Characterisation of Cdc25B localisation and nuclear export during the cell cycle and in response to stressLindqvist, AKallstrom, HKarlsson Rosenthal, CJ Cell Sci 117:4979-90inferred by electronic annotationIEAGOIEA3.1.3.16Dephosphorylation of cytoplasmic Cyclin B1/B2:phospho-Cdc2 (Thr 14, Tyr 15) complexes by CDC25BDephosphorylation of cytoplasmic Cyclin B1/B2:phospho-Cdc2 (Thr 14, Tyr 15) complexes by CDC25BThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 103201911CCNB1,CCNB2:p-T14,Y15,T161-CDK1 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 293562Converted from EntitySet in ReactomeReactome DB_ID: 103201951CCNB1,CCNB2:p-T161-CDK1 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 293722PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 103201531EQUAL580EQUALReactome Database ID Release 7510320196Database 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=10320196Reactome Database ID Release 7510320198Database 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=10320198ReactomeR-XTR-1701611Reactome 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-XTR-170161.1Activation of the mitotic cyclinB:Cdc2 (CCNB:CDK1) complexes at mitosis requires the removal of the inhibitory phosphate groups on Cdc2 (CDK1). This dephosphorylation is achieved by the activity of the CDC25 family of phosphatases, which act on both CCNB1 and CCNB2-bound CDK1 (Galaktionov and Beach 1991, Goda et al. 2003, Timofeev et al. 2010). The CDC25 members, CDC25A, CDC25B, and CDC25C are kept inactive during interphase and are activated at the G2/M transition. CCNB:CDK1 complexes appear to participate in the full activation of CDC25 in a process that involves an amplification loop (see Wolfe and Gould, 2004). The initial activation of the CCNB:CDK1 (cyclin B1:Cdc2 and cyclin-B2:Cdc2) complexes occurs in the cytoplasm in prophase (Jackman et al., 2003). CDC25B, which is present at highest concentrations in the cytoplasm at this time, is thought to trigger the activation of CCNB1:CDK1 (Lindqvist et al. 2004; Honda et al., 1993). Active CCNB1:CDK1 then phosphorylates CDC25C (contributing to its PLK1-mediated activation) and stabilizes CDC25A (Strausfeld et al., 1994; Hoffman et al.,1993; Mailand et al, 2002). This creates positive feedback loops that allows CDC25A and CDC25C to dephosphorylate and further activate CDK1. As active CDC25C is nuclear, it presumably predominantly contributes to activation of nuclear CDK1 (Strausfeld et al. 1994, Toyoshima-Morimoto et al. 2002, Bonnet, Coopman et al. 2008, Bonnet Mayonove et al. 2008). 12754270Pubmed2003The RRASK motif in Xenopus cyclin B2 is required for the substrate recognition of Cdc25C by the cyclin B-Cdc2 complexGoda, TadahiroIshii, TakashiNakajo, NobushigeSagata, NoriyukiKobayashi, HidekiJ. Biol. Chem. 278:19032-720360007Pubmed2010Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transitionTimofeev, OlegCizmecioglu, OnurSettele, FlorianKempf, ToreHoffmann, IngridJ. Biol. Chem. 285:16978-9018604163Pubmed2008Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosisBonnet, JérômeCoopman, PeterMorris, May CCell Cycle 7:1991-812411508Pubmed2002Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stabilityMailand, NPodtelejnikov, AVGroth, AMann, MLukas, JEMBO J 21:5911-201836978Pubmed1991Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclinsGalaktionov, KBeach, DCell 67:1181-948119945Pubmed1994Activation of p34cdc2 protein kinase by microinjection of human cdc25C into mammalian cells. Requirement for prior phosphorylation of cdc25C by p34cdc2 on sites phosphorylated at mitosis.Strausfeld, UFernandez, ACapony, JPGirard, FLautredou, NDerancourt, JLabbe, JCLamb, NJJ Biol Chem 269:5989-600012524548Pubmed2003Active cyclin B1-Cdk1 first appears on centrosomes in prophaseJackman, MLindon, CNigg, EAPines, JNat Cell Biol 5:143-88440392Pubmed1993Dephosphorylation of human p34cdc2 kinase on both Thr-14 and Tyr-15 by human cdc25B phosphataseHonda, ROhba, YNagata, AOkayama, HYasuda, HFEBS Lett 318:331-410827953Pubmed2000Rapid destruction of human Cdc25A in response to DNA damage.Mailand, NLukas, CSyljuâsen, RGWelcker, MLukas, JScience 288:1425-98428594Pubmed1993Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosisHoffmann, IngridClarke, PRMarcote, MJKarsenti, EDraetta, GEMBO J 12:53-63inferred by electronic annotationIEAGOIEA2.7.11Phosphorylation of Cyclin B1 in the CRS domainPhosphorylation of Cyclin B1 in the CRS domainThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103201571CCNB1:p-T161-CDK1 [cytosol]CCNB1:p-T161-CDK1Reactome DB_ID: 1032005911EQUAL433EQUALReactome DB_ID: 103146551O-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome Database ID Release 7510320157Database 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=10320157ReactomeR-XTR-1574561Reactome 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-XTR-157456.1Reactome DB_ID: 1135924Reactome DB_ID: 103200741phospho-cyclin B1(CRS):phosph-Cdc2(Thr 161) [cytosol]phospho-cyclin B1(CRS):phosph-Cdc2(Thr 161)Reactome DB_ID: 103146551O-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome DB_ID: 103200721O-phospho-L-serine at 126 (in Homo sapiens)126EQUALO-phospho-L-serine at 128 (in Homo sapiens)128EQUALO-phospho-L-serine at 133 (in Homo sapiens)133EQUALO-phospho-L-serine at 144 (in Homo sapiens)144EQUAL1EQUAL433EQUALReactome Database ID Release 7510320074Database 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=10320074ReactomeR-XTR-1700471Reactome 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-XTR-170047.1Reactome DB_ID: 293704PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10320159CRS kinase [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 7510320160Database 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=10320160Reactome Database ID Release 7510320162Database 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=10320162ReactomeR-XTR-1701261Reactome 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-XTR-170126.1At the onset of mitosis, cyclin B is phosphorylated in the CRS sequence which creates a nuclear import signal in the amino terminus. The kinase(s) responsible for this phosphorylation are not yet known (Hagting et al., 1999).inferred by electronic annotationIEAGOIEATranslocation of CRS phosphorylated Cyclin B1:Cdc2 complexesTranslocation of CRS phosphorylated Cyclin B1:Cdc2 complexesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103200741Reactome DB_ID: 103200921p-4S-CCNB1:p-T161-CDK1 [nucleoplasm]p-4S-CCNB1:p-T161-CDK1Reactome DB_ID: 103200881O-phospho-L-serine at 126 (in Homo sapiens)126EQUALO-phospho-L-serine at 128 (in Homo sapiens)128EQUALO-phospho-L-serine at 133 (in Homo sapiens)133EQUALO-phospho-L-serine at 144 (in Homo sapiens)144EQUAL1EQUAL433EQUALReactome DB_ID: 103200901O-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome Database ID Release 7510320092Database 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=10320092ReactomeR-XTR-1700811Reactome 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-XTR-170081.1Reactome Database ID Release 7510320164Database 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=10320164ReactomeR-XTR-1701311Reactome 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-XTR-170131.1The rapid translocation of cyclin B1:Cdc2 from the cytoplasm to the nucleus at the onset of mitosis is a result of an increase in the rate of import and, likely, a decreased rate of export. The increased rate of nuclear import is dependent upon phosphorylation of the CRS which creates a nuclear import signal in the amino terminus of cyclin B1 (Hagting et al, 1999).inferred by electronic annotationIEAGOIEATranslocation of Cdc25 to the nucleusTranslocation of Cdc25 to the nucleusThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 103201851CDC25 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitycdc25b [cytosol]cdc25a [cytosol]phospho-cntn1 [cytosol]Converted from EntitySet in ReactomeReactome DB_ID: 103201721CDC25 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitycdc25a [nucleoplasm]phospho-cntn1 [nucleoplasm]cdc25b [nucleoplasm]Reactome Database ID Release 7510320187Database 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=10320187ReactomeR-XTR-1701591Reactome 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-XTR-170159.1The localization of the Cdc25A, B and C proteins is dynamic involving the shuttling of these proteins between the nucleus and the cytoplasm. Sequences in these proteins mediate both nuclear export and import (Kallstrom et al., 2005; Lindqvist et al., 2004; Graves et al, 2001; Takizawa and Morgan, 2000).11313932Pubmed2001Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding.Graves, PRLovly, CMUy, GLPiwnica-Worms, HOncogene 20:1839-5115572030Pubmed2005Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and importKallstrom, HLindqvist, APospisil, VLundgren, ARosenthal, CKExp Cell Res 303:89-100inferred by electronic annotationIEAGOIEA3.1.3.16Dephosphorylation of nuclear Cyclin B1:phospho-Cdc2 (Thr 14, Tyr15) complexes by Cdc25 phosphatasesDephosphorylation of nuclear Cyclin B1:phospho-Cdc2 (Thr 14, Tyr15) complexes by Cdc25 phosphatasesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 1135182Reactome DB_ID: 103200861Reactome DB_ID: 103201701CCNB1:p-T161-CDK1 [nucleoplasm]CCNB1:p-T161-CDK1Reactome DB_ID: 1032007811EQUAL433EQUALReactome DB_ID: 103200901O-phospho-L-threonine at 161 (in Homo sapiens)161EQUAL1EQUAL297EQUALReactome Database ID Release 7510320170Database 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=10320170ReactomeR-XTR-1701601Reactome 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-XTR-170160.1Reactome DB_ID: 1135502PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10320172Reactome Database ID Release 7510320173Database 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=10320173Reactome Database ID Release 7510320175Database 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=10320175ReactomeR-XTR-1701531Reactome 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-XTR-170153.1Following its translocation to the nucleus, Cdc25 dephosphorylates and activates nuclear cyclin B1:Cdc2 complexes (Strausfeld et al., 1991).1828290Pubmed1991Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 proteinStrausfeld, ULabbe, JCFesquet, DCavadore, JCPicard, ASadhu, KRussell, PDoree, MNature 351:242-5inferred by electronic annotationIEAGOIEA2.7.11.22CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103733851UniProt:F6SF26UniProtF6SF261EQUAL763EQUALReactome DB_ID: 293581Reactome DB_ID: 103733881O-phospho-L-threonine at 611 (in Homo sapiens)611EQUAL1EQUAL763EQUALReactome DB_ID: 1135821PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10373392p-CDK1/2:CCNA/p-T161-CDK1:CCNB1 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityGO0004693GO molecular functionReactome Database ID Release 7510373395Database 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=10373395Reactome Database ID Release 7510373397Database 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=10373397ReactomeR-XTR-40880241Reactome 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-XTR-4088024.1In the G2 phase of the cell cycle, cyclin A (CCNA) and B (CCNB)-dependent kinases CDK1 and CDK2 phosphorylate FOXM1 transcription factor, increasing its transcriptional activity. Threonine residue T611 (corresponds to T596 in FOXM1B isoform) was shown to be phosphorylated by both CCNA:CDK1/2 and CCNB:CDK1 complexes and its functional relevance is best establshed (Major et al. 2004, Laoukili et al. 2008, Fu et al. 2008). CCNA:CDK1/2 may also phosphorylate FOXM1 on T600 (Laoukili et al. 2008), while CCNB:CDK1 may phosphorylate it on S693 (S678 in FOXM1B isoform) (Fu et al. 2008). The phosphorylation of FOXM1 threonine residue T611 relieves the N-terminal domain-mediated autoinhibition of FOXM1 transcriptional activity (Laoukili et al. 2008), likely enabling interaction with transcriptional co-activators (Major et al. 2004), and creates a docking site for the Polo-box domain (PBD) of PLK1 (Fu et al. 2008).19160488Pubmed2008Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progressionFu, ZhengMalureanu, LiviuHuang, JWang, WeiLi, Hvan Deursen, Jan MTindall, Donald JChen, JNat. Cell Biol. 10:1076-8218285455Pubmed2008Activation of FoxM1 during G2 requires cyclin A/Cdk-dependent relief of autorepression by the FoxM1 N-terminal domainLaoukili, JamilaAlvarez, MonicaMeijer, Lars A TStahl, MarieMohammed, ShabazKleij, LivioHeck, Albert J RMedema, René HMol. Cell. Biol. 28:3076-8715024056Pubmed2004Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivatorsMajor, Michael LLepe, RitaCosta, Robert HMol. Cell. Biol. 24:2649-61inferred by electronic annotationIEAGOIEAPP2A-PPP2R2A dephosphorylates FOXM1PP2A-PPP2R2A dephosphorylates FOXM1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 1135181Reactome DB_ID: 103733881O-phospho-L-threonine at 611 (in Homo sapiens)611EQUAL1EQUAL763EQUALReactome DB_ID: 1037338511EQUAL763EQUALReactome DB_ID: 1135501PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10373410PP2A-PPP2R2A [nucleoplasm]PP2A-PPP2R2AReactome DB_ID: 103548161UniProt:F7AB62atrxUniProtF7AB622EQUAL447EQUALConverted from EntitySet in ReactomeReactome DB_ID: 103548041PP2A-subunit A [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 103548101PP2A-catalytic subunit C [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 7510373410Database 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=10373410ReactomeR-XTR-40881421Reactome 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-XTR-4088142.1GO0004722GO molecular functionReactome Database ID Release 7510373411Database 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=10373411Reactome Database ID Release 7510373413Database 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=10373413ReactomeR-XTR-40881411Reactome 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-XTR-4088141.1FOXM1 can bind the regulatory subunit B55-alpha (PPP2R2A) of serine/threonine-protein phosphatase 2A (PP2A). PP2A dephosphorylates FOXM1, preventing its premature activation (Alvarez-Fernandez et al. 2011).21813648Pubmed2011Protein phosphatase 2A (B55?) prevents premature activation of forkhead transcription factor FoxM1 by antagonizing cyclin A/cyclin-dependent kinase-mediated phosphorylationAlvarez-Fernández, MónicaHalim, Vincentius AAprelia, MelindaLaoukili, JamilaMohammed, ShabazMedema, René HJ. Biol. Chem. 286:33029-36inferred by electronic annotationIEAGOIEA2.1.1PP2A methylation by LCMT1PP2A methylation by LCMT1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103548201PP2A [nucleoplasm]PP2AConverted from EntitySet in ReactomeReactome DB_ID: 103548181PPP2R3B,PPP2R2A [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 103548041Converted from EntitySet in ReactomeReactome DB_ID: 103548101Reactome Database ID Release 7510354820Database 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=10354820ReactomeR-XTR-13632651Reactome 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-XTR-1363265.1Reactome DB_ID: 770871S-adenosyl-L-methionine [ChEBI:15414]S-adenosyl-L-methionineChEBI15414Reactome DB_ID: 775021S-adenosyl-L-homocysteine [ChEBI:16680]S-adenosyl-L-homocysteineChEBI16680Reactome DB_ID: 103981771MeL-PP2A [nucleoplasm]MeL-PP2AConverted from EntitySet in ReactomeReactome DB_ID: 103548181Converted from EntitySet in ReactomeReactome DB_ID: 103981751MeL-PPP2CA,MeL-PPP2CB [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 103548041Reactome Database ID Release 7510398177Database 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=10398177ReactomeR-XTR-88577871Reactome 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-XTR-8857787.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10398181UniProt:F6WLS5lcmt1UniProtF6WLS51EQUAL334EQUALGO0018423GO molecular functionReactome Database ID Release 7510398182Database 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=10398182Reactome Database ID Release 7510398184Database 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=10398184ReactomeR-XTR-88569451Reactome 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-XTR-8856945.1Reversible methylation of the PP2A C subunit is a highly conserved and essential regulatory mechanism (Lee et al. 1996). Methylation of the carboxy-termius of PP2A C enhances the affinity of the PP2A core enzyme for some regulatory subunits (Xing et al. 2008). Changes in PP2A methylation appear to regulate formation of PP2A complexes and alter the specificity of PP2A phosphatase activity (Mumby 2001). Blockade of PP2A methylation in yeast causes a set of phenotypes that are consistent with decreased formation of PP2A holoenzymes (Wu et al. 2000). Reversible methylation of PP2A is catalyzed by two highly conserved enzymes, a 38 kDa leucine carboxyl methyltransferase (LCMT1) (De Baere et al. 1999, Lee & Stock 1993) and a 42 kDa methylesterase (PPME1) (Lee et al. 1996, Ogris et al. 1999). PP2A carboxy-methylation by LCMT1 requires an active PP2A conformation and is significantly facilitated by the PP2A scaffold (or A) subunit (Stanevich et al. 2011, Stanevich et al. 2014). LCMT1 also methylates the PP2A-like phosphatases PP4 and PP6 (Hwang et al. 2016). PPME1 catalyzes removal of the methyl group, thus reversing the activity of LCMT1 (Lee et al. 1996). Overexpression of yeast PPME caused phenotypes similar to those associated with loss of the methyltransferase gene (Wu et al. 2000). <br><br>Methylation and demethylation are spatially separated within mammalian cells, as the majority of LCMT1 is cytoplasmic and PPME1 predominantly localizes in the nucleus (Longin et al. 2008). In mammalian cells, LCMT1 knockdown results in apoptotic cell death (Longin et al. 2007). In mice, LCMT1 or PPME1 knockout are lethal (Lee & Pallas 2007, Ortega-Gutiérrez et al. 2008). Methylation levels of PP2A change during the cell cycle, suggesting a critical role of methylation in cell-cycle regulation (Turowski et al. 1995, Lee & Pallas 2007). Regulation of PP2A methylation by LCMT1 and PPME1 plays a critical role in differentiation of neuroblastoma cells (Sontag et al. 2010). Decreased PP2A methylation in Alzheimer’s and Parkinson’s disease patients contributes to PP2A inactivation and increased phosphorylation of tau and alpha-synuclein (Sontag & Sontag 2014, Park et al. 2016). PPME1 may also inhibit PP2A by sequestration (Longin et al. 2004) and/or by evicting catalytic metal ions from the PP2A active site (Xing et al. 2008). As such, increased PPME1 expression suppresses PP2A tumor suppressive function and promotes oncogenic MAPK/ERK and AKT pathway activities in various cancer types (Kaur & Westermarck 2016). PPME1 may also protect PP2A from ubiquitin/proteasome degradation (Yabe et al. 2015).24466300Pubmed2014Mechanisms of the scaffold subunit in facilitating protein phosphatase 2A methylationStanevich, VitaliZheng, AipingGuo, FengJiang, LiWlodarchak, NathanXing, YongnaPLoS ONE 9:e8695521292165Pubmed2011The structural basis for tight control of PP2A methylation and function by LCMT-1Stanevich, VitaliJiang, LiSatyshur, Kenneth ALi, YongfengJeffrey, Philip DLi, ZhuMenden, PatrickSemmelhack, Martin FXing, YongnaMol. Cell 41:331-4221044074Pubmed2010Regulation of protein phosphatase 2A methylation by LCMT1 and PME-1 plays a critical role in differentiation of neuroblastoma cellsSontag, Jean-MarieNunbhakdi-Craig, ViyadaMitterhuber, MartinaOgris, EgonSontag, EstelleJ. Neurochem. 115:1455-6518596935Pubmed2008Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in miceOrtega-Gutiérrez, SilviaLeung, DonmienneFicarro, ScottPeters, Eric CCravatt, BFPLoS ONE 3:e24868396127Pubmed1993Protein phosphatase 2A catalytic subunit is methyl-esterified at its carboxyl terminus by a novel methyltransferaseLee, JStock, JJ. Biol. Chem. 268:19192-518291659Pubmed2008PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail)Janssens, VeerleLongin, SariGoris, JozefTrends Biochem. Sci. 33:113-2114748741Pubmed2004An inactive protein phosphatase 2A population is associated with methylesterase and can be re-activated by the phosphotyrosyl phosphatase activatorLongin, SariJordens, JanMartens, EllenStevens, IlseJanssens, VeerleRondelez, EvelienDe Baere, IvoDerua, RitaWaelkens, EGoris, JozefVan Hoof, ChristineBiochem. J. 380:111-917724024Pubmed2007Leucine carboxyl methyltransferase-1 is necessary for normal progression through mitosis in mammalian cellsLee, Jocelyn APallas, David CJ. Biol. Chem. 282:30974-8427752512Pubmed2016Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodiesPark, Hye-JinLee, Kang-WooPark, Eun SOh, StephanieYan, RunZhang, JBeach, Thomas GAdler, Charles HVoronkov, MichaelBraithwaite, Steven PStock, Jeffry BMouradian, M MaralAnn Clin Transl Neurol 3:769-7807721943Pubmed1995Differential methylation and altered conformation of cytoplasmic and nuclear forms of protein phosphatase 2A during cell cycle progressionTurowski, PFernandez, AFavre, BLamb, N JHemmings, B AJ. Cell Biol. 129:397-41017803990Pubmed2008Spatial control of protein phosphatase 2A (de)methylationLongin, SariZwaenepoel, KarenMartens, EllenLouis, Justin VRondelez, EvelienGoris, JozefJanssens, VeerleExp. Cell Res. 314:68-8111752649Pubmed2001A new role for protein methylation: switching partners at the phosphatase ballMumby, MSci. STKE 2001:pe126678046Pubmed2015Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin/Proteasome DegradationYabe, RyotaroMiura, AkaneUsui, TatsuyaMudrak, IngridOgris, EgonOhama, TakashiSato, KoichiPLoS ONE 10:e014522611060018Pubmed2000Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivoWu, JTolstykh, TLee, JBoyd, KStock, J BBroach, J REMBO J. 19:5672-8110600115Pubmed1999Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologueDe Baere, IDerua, RJanssens, VVan Hoof, CWaelkens, EMerlevede, WGoris, JBiochemistry 38:16539-478650216Pubmed1996A specific protein carboxyl methylesterase that demethylates phosphoprotein phosphatase 2A in bovine brainLee, JChen, YTolstykh, TStock, JProc. Natl. Acad. Sci. U.S.A. 93:6043-710318862Pubmed1999A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2AOgris, EDu, XNelson, K CMak, E KYu, X XLane, WSPallas, D CJ. Biol. Chem. 274:14382-9118394995Pubmed2008Structural mechanism of demethylation and inactivation of protein phosphatase 2AXing, YongnaLi, ZhuChen, YuStock, Jeffry BJeffrey, Philip DShi, YCell 133:154-6327507813Pubmed2016Leucine Carboxyl Methyltransferase 1 (LCMT-1) Methylates Protein Phosphatase 4 (PP4) and Protein Phosphatase 6 (PP6) and Differentially Regulates the Stable Formation of Different PP4 HoloenzymesHwang, JuyeonLee, Jocelyn APallas, David CJ. Biol. Chem. 291:21008-2101917635907Pubmed2007Selection of protein phosphatase 2A regulatory subunits is mediated by the C terminus of the catalytic SubunitLongin, SariZwaenepoel, KarenLouis, Justin VDilworth, StephenGoris, JozefJanssens, VeerleJ. Biol. Chem. 282:26971-8027913678Pubmed2016Regulation of protein phosphatase 2A (PP2A) tumor suppressor function by PME-1Kaur, AmanpreetWestermarck, JukkaBiochem. Soc. Trans. 44:1683-1693inferred by electronic annotationIEAGOIEAPP2A demethylation by PPME1PP2A demethylation by PPME1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 103981771Reactome DB_ID: 1135181Reactome DB_ID: 103548201Reactome DB_ID: 88577971methanol [ChEBI:17790]methanolChEBI17790PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10398188UniProt:F7AWU4ppme1UniProtF7AWU42EQUAL386EQUALGO0051722GO molecular functionReactome Database ID Release 7510398189Database 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=10398189Reactome Database ID Release 7510398191Database 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=10398191ReactomeR-XTR-88569511Reactome 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-XTR-8856951.1The reversible methylation of the PP2A C subunit is a highly conserved and essential regulatory mechanism (Lee et al. 1996). Methylation of the carboxy-termius of PP2A C enhances the affinity of the PP2A core enzyme for some regulatory subunits (Xing et al. 2008). Changes in PP2A methylation appear to regulate formation of PP2A complexes and alter the specificity of PP2A phosphatase activity (Mumby 2001). Blockade of PP2A methylation in yeast causes a set of phenotypes that are consistent with decreased formation of PP2A holoenzymes (Wu et al. 2000). Reversible methylation of PP2A is catalyzed by two highly conserved enzymes, a 38 kDa leucine carboxyl methyltransferase (LCMT1) (De Baere et al. 1999, Lee & Stock 1993) and a 42 kDa methylesterase (PPME1) (Lee et al. 1996, Ogris et al. 1999). PP2A carboxy-methylation by LCMT1 requires an active PP2A conformation and is significantly facilitated by the PP2A scaffold (or A) subunit (Stanevich et al. 2011, Stanevich et al. 2014). LCMT1 also methylates the PP2A-like phosphatases PP4 and PP6 (Hwang et al. 2016). PPME1 catalyzes removal of the methyl group, thus reversing the activity of LCMT1 (Lee et al. 1996). Overexpression of yeast PPME caused phenotypes similar to those associated with loss of the methyltransferase gene (Wu et al. 2000). <br><br>Methylation and demethylation are spatially separated within mammalian cells, as the majority of LCMT1 is cytoplasmic and PPME1 predominantly localizes in the nucleus (Longin et al. 2008). In mammalian cells, LCMT1 knockdown results in apoptotic cell death (Longin et al. 2007). In mice, LCMT1 or PPME1 knockout are lethal (Lee & Pallas 2007, Ortega-Gutiérrez et al. 2008). Methylation levels of PP2A change during the cell cycle, suggesting a critical role of methylation in cell-cycle regulation (Turowski et al. 1995, Lee & Pallas 2007). Regulation of PP2A methylation by LCMT1 and PPME1 plays a critical role in differentiation of neuroblastoma cells (Sontag et al. 2010). Decreased PP2A methylation in Alzheimer’s and Parkinson’s disease patients contributes to PP2A inactivation and increased phosphorylation of tau and alpha-synuclein (Sontag & Sontag 2014, Park et al. 2016). PPME1 may also inhibit PP2A by sequestration (Longin et al. 2004) and/or by evicting catalytic metal ions from the PP2A active site (Xing et al. 2008). As such, increased PPME1 expression suppresses PP2A tumor suppressive function and promotes oncogenic MAPK/ERK and AKT pathway activities in various cancer types (Kaur & Westermarck 2016). PPME1 may also protect PP2A from ubiquitin/proteasome degradation (Yabe et al. 2015).inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510410320Database 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=10410320ReactomeR-XTR-692731Reactome 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-XTR-69273.1Cell cycle progression is regulated by cyclin-dependent protein kinases at both the G1/S and the G2/M transitions. The G2/M transition is regulated through the phosphorylation of nuclear lamins and histones (reviewed in Sefton, 2001).<br>The two B-type cyclins localize to different regions within the cell and are thought to have specific roles as CDK1-activating subunits (see Bellanger et al., 2007). Cyclin B1 is primarily cytoplasmic during interphase and translocates into the nucleus at the onset of mitosis (Jackman et al., 1995; Hagting et al., 1999). Cyclin B2 colocalizes with the Golgi apparatus and contributes to its fragmentation during mitosis (Jackman et al., 1995; Draviam et al., 2001).18228324Pubmed2001Overview of protein phosphorylationSefton, BMCurr Protoc Cell Biol 14:Unit 14.1inferred by electronic annotationIEAGOIEA