Mitotic G1 phase and G1/S transition (Homo sapiens)

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6410, 4615, 4053283, 4, 13, 551, 36, 413731, 5543171934291414116, 50, 61, 631, 271725, 31, 552, 5, 16, 18, 22...127, 6244, 49262045, 56282864133913662839932342637, 584732, 667, 14, 626021, 25, 5124cytosolnucleoplasmPPP2R1B SKP2 CDC6 ATPorigin of replication UBC(305-380) ORC5 RPA4 CCNE2 MCM4 p-CDK2 PPP2CB ORC4 ORC4 CCND3 CDK1 DNA primer MCM5 p-RB1 MCM4 UBC(153-228) RB1:TFDP1:E2F1-3PSMC6 CDC45 RNA primer UBC(533-608) E2F1 CDK1 DNA polymerasealpha:primase:DNApolymerasealpha:origincomplexPSMB4 UBB(77-152) MCM3 INK4ARBL2MCM4 ORC3 CCNB1 TYMS CCNE2 cyclin CCND1 ORC1 PKMYT1CCNA CDK4 PSME1 CCNA SKP1 RPS27A(1-76) CDC7 ORC6 RNA primer:origin duplex with DNA damage E2F1:TFDP1ADPTFDP2 CUL1:SKP1:SKP2UBC(229-304) CDKN1A RB1 PSMA1 PPP2R1A CCNH PRIM1 PSMB6 CDK2 H2OMCM4 CCND2 CDC6 Ub-p-T401,S672,1035-RBL2cyclin ORC4 DBF4 E2F4 ORC6 TFDP2 UBC(305-380) CCNE1 MAX Cyclin E:p-CDK2PSMD9 POLA1 E2F4 ORC1 UBC(457-532) RBL1CDKN1A PSMC2 MCM10:pre-replicative complexTFDP2 p-MuvB complexE2F3 E2F3 CKS1B CDK2 ORC2 PSMB5 UBC(229-304) CUL1 p-CDK2 ATPPSMB7 origin of replication PSMB8 CCNE1 ORC6 RB1 RBL1:E2F4:TFDP1,TFDP2PSMA5 H2Ocyclin UBC(457-532) RNA primer:origin duplex with DNA damage CDC6 MCM7 CCND2 PSMC4 TFDP1 MCM7 DNA polymeraseepsilon:origincomplexCCNE1 p-T401,S672,S1035-RBL2 UBC(381-456) MCM5 CCNE1 ATPATPCDKN1A RPA3 UBC(77-152) ORC5 CDT1 TFDP2 origin of replication PSMD13 UBB(1-76) CKS1B p-MCM2-7CCNE1 origin of replication CDK2 CDKN2C CDC25AHDAC1MCM7 RB1 RB1 PPP2CA CDK2 ORC2 CDC7 ADPRBL1 RBL2 ORC3 PSMD14 RBL2 p-S130-CDKN1A UbiquitinSKP2 MuvB complexCyclinD:CDK4,CDK6:CDKN1A,CDKN1Bp-S28-LIN52 CDKN1B CCNA1 origin of replication PSMC5 MCM5 MCM2-7UBB(1-76) ADPCDT1 PiE2F4 CCNE2 CDKN1B TFDP1 E2F1 CyclinE/A:CDK2:CDKN1A,CDKN1BCDK2 TFDP2 ORC4 RPA1-4CCNE2 MCM8 MCM10CUL1 CDK2 CKS1BRBL1:E2F4:TFDP1,TFDP2MCM6 CDKN1Ap-T401,S672,S1035-RBL2SKP2 PSMA6 RB1ATPPPP2R3B PPP2R1B CDK4,CDK6p-Y88-CDKN1B ORC2 CUL1:SKP1:SKP2:CKS1BDDKUBA52(1-76) RBL1LIN37 POLE2 E2F5 LIN54 CKS1B CCND1 MCM4 ORC3 CDKN1Ap-T401,S672,1035-RBL2:SCF(Skp2):Cks1SKP2 UBC(1-76) MCM6 p-S130-CDKN1A MCM7 MCM6 MCM2 MCM2 RPA2 CKS1B CCNE2 SKP1 ADPCCNE1 UBC(381-456) CDKN2C RBL1 PSMD10 CCNE1 UBC(1-76) CDKN1A,CDKN1BRBL2:E2F4,E2F5:TFDP1,TFDP2CyclinE:p-T160-CDK2:RB1CCNAATPE2F1Cyclin E:p-T160-CDK2CUL1 CDK4,CDK6PSMD8 DNA primer PSMD11 CDC6MCM4 CCNE1 CCNE1:CDK2CDK7 CDC7 ADPRBL2 PSMD3 ATPMCM5 RNA primer:origin duplex with DNA damage UBC(77-152) SKP1 CKS1B RBL2:Cyclin E/A:CDK2DHFR MCM2 MCM7 TFDP1 RPA2 UBC(457-532) MNAT1 CCNE2 UBC(609-684) PSMA4 ADPORC6 TFDP1 MCM5 CDK2 CDC6 PSMD4 Cyclin E CDKN1B CCNE1 ORC:origin ofreplicationPOLE PSMD6 ORC6 Cyclin E/A:CDK2RPA1 ORC5 DBF4 origin of replication ORC1 TFDP2 MCM2 CDK2 MCM10 Cyclin B:CDK1p-T160-CDK2 p-T160-CDK2 RRM2 CDKN1BMCM10 E2F1 CDK2 CCNE2 ORC5 LIN54 TFDP1:E2F1-3MCM3 RBL2 LIN37 origin of replication DREAM complexORC5 ADPDNA polymeraseepsilonRBL2:E2F4/5:DP1/2:Cyclin E/A:CDK2CyclinD:CDK4,CDK6:CDKN1A,CDKN1BUBC(305-380) CDK4,CDK6:INK4Ap-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))MCM3 MCM7 ORC3 PPP2R3B PRIM2 CDKN1A MCM3 ORC1 DYRK1Ap-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))MCM10:activepre-replicativecomplexPPP2CB CCNE1 ORC1 RBL1:Cyclin E/A:CDK2MCM6 CDC25A PSMD7 UBB(153-228) LIN9 26S proteasomeUBA52(1-76) ORC6 CCNA1 RBL2SKP2 CDC45 POLA1 p-Y342-PTK6 DBF4 E2F5 Cyclin DTK2 RNA primer-DNAprimer:originduplexMCM8 CDK6 MCM8 MCM3 CDKN2B CCNE1 p-T177-CDK6 PP2ACDKN1B CDK6 TFDP1 E2F5 MYC ORC4 RBL1 CCNE1 CDK2 MCM8 Pi LIN54 ATPCyclinD:p-CDK4,p-CDK6:CDKN1A,CDKN1BCDK6 CDK4 E2F5 CDKN1B DBF4 CDC6 PSMB1 CCND1 MCM5 CUL1:SKP1:SKP2:CKS1BUbiquitinp16-INK4a E2F5 POLA1 CDK4 TFDP1 CDK2 Aborted replicationcomplexPiMCM2 p-T172-CDK4 CCNA2 DNA primer CDK2 Cyclin E Cyclin E CCNE1 CDC45POLE2 PSMD5 PSMA7 RBBP4 MYBL2SKP1 p-T369,S640,S964,S975-RBL1Cyclin E POLE CCND1 p-T401,S672,S1035-RBL2 CCNE2 LIN52 CCNA CCND2 CyclinE:CDK2:CDKN1A,CDKN1BCAKCyclin E CDK4 ADPUBC(153-228) PSMD2 CCNA CCND3 p-T187-CDKN1B UBB(153-228) CCNB1 RBL2:E2F4,E2F5:TFDP1,TFDP2p16-INK4a TFDP2 CDK2 CCNE2 UBB(77-152) CCNE2:CDK2CDKN2D ORC3 RPS27A(1-76) PSMC3 CDK:DDK:MCM10:activepre-replicativecomplex:CDC45:RPA1-4MCM6 ORC5 MCM10 UBC(533-608) UBC(77-152) POLE p-S28-LIN52 ORC5 MCM10 E2F4 E2F4 MCM7 POLA1 ATPRPA3 ORC1 MCM2 RNA primer-DNAprimer:originduplex with DNAdamageCCND1 UBC(381-456) TFDP1 E2F4 RPA4 PPP2R1B SKP2 RBL1 PSMA3 ORC6 DNA polymerasealpha:primasePRIM1 PRIM1 CCNE2 CUL1 origin of replication MCM4 CDC6 TOP2ACDK4 MCM5 RPS27A(1-76) CDKN2D UBB(1-76) E2F2 TFDP2 CyclinB:CDK1:ORC:originof replicationCDKN2B TFDP1 CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BE2F4,E2F5:TFDP1,TFDP2RB1:RNA primer-DNAprimer:originduplex with DNAdamageCDK4 TFDP1 ADPCCND2 MCM6 CCNA CCNA E2F4 Cyclin E origin of replication ORC6 RBBP4 E2F1 targetsE2F4 CDKN1A E2F4 ORC4 p-T160-CDK2 CDKN1A CCNE2:p-CDK2PSMB3 PSMB10 E2F4 MCM2 CUL1 CCNA MYC:MAXRBL2 TFDP1 ADPCDKN1B Cyclin E PPP2CA TFDP1 ORC4 TFDP2 UBB(77-152) origin ofreplicationCDKN1B UBC(381-456) p-CDK2 ORC1 PCNA RBBP4 ORC2 PPP2CB MCM6 CDK1 CDK4 FBXO5 UBC(77-152) ATPCCNE1:p-CDK2POLA2 PPP2R2A PSMA2 E2F4:TFDP1,TFDP2PCNAUBC(153-228) PSMD1 CDK6 Cyclin E CDK2 p-S130-CDKN1A ORC2 E2F5 ADPCDK1CDK2 UBB(153-228) RPA1 Cyclin EHDAC1 Cyclin E:CDK2POLA2 UBB(1-76) POLE2 ORC3 CDC6 origin of replication PPP2R1A PRIM2 CDK2 CDK2 p-T187-CDKN1B ORC1 MCM2 UBC(1-76) LIN9 UBC(533-608) CDKN1A PP2ACDK2 CDK2WEE1CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinRBL1 CDK2 POLA2 CDKN1BTFDP1 UBC(533-608) CCND3 PPP2R2A MCM8 UBC(457-532) RBL1ORC3 PSMD12 CDK6 UBC(1-76) HDAC1:RBL2:E2F4/5:DP1/2CDKN1B LIN9 H2OPPP2CA UBA52(1-76) HDAC1:RBL1:E2F4:TFDP1,TFDP2CDK2 MCM3 UBC(609-684) pre-replicativecomplexHDAC1 TFDP2 origin of replication CCND3 UBC(153-228) CCNE:CDK2ORC3 CCNE1 ATPCDC25AUBB(77-152) CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))PP2AUBC(305-380) PRIM2 CDKN1A,CDKN1BCDK4 CDT1 TFDP1 MCM6 MCM10 E2F4 CCND1 CCNA UBC(229-304) LIN37 E2F2 MCM4 p-Y342-PTK6UBB(153-228) PPP2R1A ORC2 PSMF1 cyclin CUL1 ORC2 CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1BUBC(609-684) PSME2 CDK:DDK:MCM10:activepre-replicativecomplex:CDC45ORC2 MCM3 p-T187-CDKN1B TFDP2 CDK2 TFDP1 ORC1 CCNA CCND1 CDC45 MCM8 CDT1CyclinE:p-T160-CDK2:p-RB1ATPMCM8 Cyclin E MCM7 ORC5 SKP1 UBC(609-684) PSME3 MCM8 PSMC1 CDC7 CDKN1B ADPADPORC4 PSMB9 TFDP1 p-S795-RB1E2F1RPS27A(1-76) SKP1 UBC(229-304) CDK:DDK:MCM10:activepre-replicativecomplexMCM5 RBL1:E2F4:DP1/2:Cyclin E/A:CDK2RBL2 CDKUBA52(1-76) E2F1 PPP2R3B MCM3 DNA primer PiPSMB2 ATP10, 463730, 4833592835378


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  205. Niehof M, Streetz K, Rakemann T, Bischoff SC, Manns MP, Horn F, Trautwein C.; ''Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPbeta promoter suggests a new mechanism of transcriptional regulation by STAT3.''; PubMed Europe PMC Scholia
  206. Lukong KE, Larocque D, Tyner AL, Richard S.; ''Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression.''; PubMed Europe PMC Scholia
  207. Cheng M, Sexl V, Sherr CJ, Roussel MF.; ''Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1).''; PubMed Europe PMC Scholia
  208. Atwood AA, Sealy L.; ''Regulation of C/EBPbeta1 by Ras in mammary epithelial cells and the role of C/EBPbeta1 in oncogene-induced senescence.''; PubMed Europe PMC Scholia
  209. Jiang W, Wells NJ, Hunter T.; ''Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.''; PubMed Europe PMC Scholia
  210. Leng X, Noble M, Adams PD, Qin J, Harper JW.; ''Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4.''; PubMed Europe PMC Scholia
  211. Zheng Y, Asara JM, Tyner AL.; ''Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 CRK-associated substrate.''; PubMed Europe PMC Scholia
  212. Orend G, Hunter T, Ruoslahti E.; ''Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells.''; PubMed Europe PMC Scholia
  213. Bagui TK, Jackson RJ, Agrawal D, Pledger WJ.; ''Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1).''; PubMed Europe PMC Scholia
  214. Tedesco D, Lukas J, Reed SI.; ''The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2).''; PubMed Europe PMC Scholia
  215. Yu B, Lane ME, Pestell RG, Albanese C, Wadler S.; ''Downregulation of cyclin D1 alters cdk 4- and cdk 2-specific phosphorylation of retinoblastoma protein.''; PubMed Europe PMC Scholia
  216. Agger K, Cloos PA, Rudkjaer L, Williams K, Andersen G, Christensen J, Helin K.; ''The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence.''; PubMed Europe PMC Scholia
  217. Ono H, Basson MD, Ito H.; ''PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.''; PubMed Europe PMC Scholia
  218. Reynisdóttir I, Massagué J.; ''The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2.''; PubMed Europe PMC Scholia
  219. Dietrich N, Bracken AP, Trinh E, Schjerling CK, Koseki H, Rappsilber J, Helin K, Hansen KH.; ''Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus.''; PubMed Europe PMC Scholia
  220. Castro NE, Lange CA.; ''Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells.''; PubMed Europe PMC Scholia
  221. Lundberg AS, Weinberg RA.; ''Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes.''; PubMed Europe PMC Scholia
  222. Bertoli C, Klier S, McGowan C, Wittenberg C, de Bruin RA.; ''Chk1 inhibits E2F6 repressor function in response to replication stress to maintain cell-cycle transcription.''; PubMed Europe PMC Scholia
  223. Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K.; ''EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.''; PubMed Europe PMC Scholia
  224. Galaktionov K, Chen X, Beach D.; ''Cdc25 cell-cycle phosphatase as a target of c-myc.''; PubMed Europe PMC Scholia
  225. DeGregori J, Kowalik T, Nevins JR.; ''Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes.''; PubMed Europe PMC Scholia
  226. Ohtani K, DeGregori J, Leone G, Herendeen DR, Kelly TJ, Nevins JR.; ''Expression of the HsOrc1 gene, a human ORC1 homolog, is regulated by cell proliferation via the E2F transcription factor.''; PubMed Europe PMC Scholia
  227. Vigo E, Müller H, Prosperini E, Hateboer G, Cartwright P, Moroni MC, Helin K.; ''CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase.''; PubMed Europe PMC Scholia
  228. Chu I, Sun J, Arnaout A, Kahn H, Hanna W, Narod S, Sun P, Tan CK, Hengst L, Slingerland J.; ''p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.''; PubMed Europe PMC Scholia
  229. Hiebert SW.; ''Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression.''; PubMed Europe PMC Scholia
  230. Goel RK, Lukong KE.; ''Tracing the footprints of the breast cancer oncogene BRK - Past till present.''; PubMed Europe PMC Scholia
  231. Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G, Hara E.; ''Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.''; PubMed Europe PMC Scholia
  232. Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF.; ''Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.''; PubMed Europe PMC Scholia
  233. Ikeda O, Mizushima A, Sekine Y, Yamamoto C, Muromoto R, Nanbo A, Oritani K, Yoshimura A, Matsuda T.; ''Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells.''; PubMed Europe PMC Scholia
  234. Ikeda O, Sekine Y, Mizushima A, Nakasuji M, Miyasaka Y, Yamamoto C, Muromoto R, Nanbo A, Oritani K, Yoshimura A, Matsuda T.; ''Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.''; PubMed Europe PMC Scholia
  235. Zheng Y, Peng M, Wang Z, Asara JM, Tyner AL.; ''Protein tyrosine kinase 6 directly phosphorylates AKT and promotes AKT activation in response to epidermal growth factor.''; PubMed Europe PMC Scholia
  236. Chen HY, Shen CH, Tsai YT, Lin FC, Huang YP, Chen RH.; ''Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin.''; PubMed Europe PMC Scholia
  237. Ganoth D, Bornstein G, Ko TK, Larsen B, Tyers M, Pagano M, Hershko A.; ''The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27.''; PubMed Europe PMC Scholia
  238. Vidal A, Koff A.; ''Cell-cycle inhibitors: three families united by a common cause.''; PubMed Europe PMC Scholia
  239. Walter J, Newport J.; ''Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.''; PubMed Europe PMC Scholia
  240. Li Y, Pursell ZF, Linn S.; ''Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.''; PubMed Europe PMC Scholia
  241. Clifton AD, Young PR, Cohen P.; ''A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress.''; PubMed Europe PMC Scholia
  242. Ben-Levy R, Leighton IA, Doza YN, Attwood P, Morrice N, Marshall CJ, Cohen P.; ''Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2.''; PubMed Europe PMC Scholia
  243. Montagnoli A, Fiore F, Eytan E, Carrano AC, Draetta GF, Hershko A, Pagano M.; ''Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.''; PubMed Europe PMC Scholia
  244. Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT, Nuckolls F, Giangrande P, Wright FA, Field SJ, Greenberg ME, Orkin S, Nevins JR, Robinson ML, Leone G.; ''The E2F1-3 transcription factors are essential for cellular proliferation.''; PubMed Europe PMC Scholia
  245. Vijayachandra K, Lee J, Glick AB.; ''Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model.''; PubMed Europe PMC Scholia
  246. Gao Y, Cimica V, Reich NC.; ''Suppressor of cytokine signaling 3 inhibits breast tumor kinase activation of STAT3.''; PubMed Europe PMC Scholia
  247. Takekawa M, Tatebayashi K, Saito H.; ''Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases.''; PubMed Europe PMC Scholia
  248. Moiseeva O, Mallette FA, Mukhopadhyay UK, Moores A, Ferbeyre G.; ''DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation.''; PubMed Europe PMC Scholia
  249. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y.; ''pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene.''; PubMed Europe PMC Scholia
  250. Lal A, Kim HH, Abdelmohsen K, Kuwano Y, Pullmann R, Srikantan S, Subrahmanyam R, Martindale JL, Yang X, Ahmed F, Navarro F, Dykxhoorn D, Lieberman J, Gorospe M.; ''p16(INK4a) translation suppressed by miR-24.''; PubMed Europe PMC Scholia
  251. Kardinal C, Dangers M, Kardinal A, Koch A, Brandt DT, Tamura T, Welte K.; ''Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4.''; PubMed Europe PMC Scholia
  252. Cobrinik D.; ''Pocket proteins and cell cycle control.''; PubMed Europe PMC Scholia
  253. Fan G, Lin G, Lucito R, Tonks NK.; ''Protein-tyrosine phosphatase 1B antagonized signaling by insulin-like growth factor-1 receptor and kinase BRK/PTK6 in ovarian cancer cells.''; PubMed Europe PMC Scholia
  254. Aprelikova O, Xiong Y, Liu ET.; ''Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by the CDK-activating kinase.''; PubMed Europe PMC Scholia
  255. Sgouras DN, Athanasiou MA, Beal GJ, Fisher RJ, Blair DG, Mavrothalassitis GJ.; ''ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114646view16:11, 25 January 2021ReactomeTeamReactome version 75
113094view11:15, 2 November 2020ReactomeTeamReactome version 74
112328view15:25, 9 October 2020ReactomeTeamReactome version 73
112225view14:39, 2 October 2020DeSlOntology Term : 'M/G1 transition pathway' added !
101227view11:12, 1 November 2018ReactomeTeamreactome version 66
100765view20:38, 31 October 2018ReactomeTeamreactome version 65
100309view19:15, 31 October 2018ReactomeTeamreactome version 64
99855view15:59, 31 October 2018ReactomeTeamreactome version 63
99413view14:35, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93757view13:34, 16 August 2017ReactomeTeamreactome version 61
93279view11:19, 9 August 2017ReactomeTeamreactome version 61
86357view09:16, 11 July 2016ReactomeTeamreactome version 56
83315view10:46, 18 November 2015ReactomeTeamVersion54
81454view12:59, 21 August 2015ReactomeTeamVersion53
76928view08:20, 17 July 2014ReactomeTeamFixed remaining interactions
76633view12:00, 16 July 2014ReactomeTeamFixed remaining interactions
76130view12:48, 11 June 2014Anwesha
76129view12:44, 11 June 2014ReactomeTeamAdding missing reactome URL
75666view10:57, 10 June 2014ReactomeTeamReactome 48 Update
75021view13:53, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74665view08:43, 30 April 2014ReactomeTeamReactome46
68884view17:26, 8 July 2013MaintBotUpdated to 2013 gpml schema
44912view10:35, 6 October 2011MartijnVanIerselOntology Term : 'cell cycle pathway, mitotic' added !
42076view21:55, 4 March 2011MaintBotAutomatic update
39884view05:54, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-177750 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Aborted replication complexComplexR-HSA-113648 (Reactome)
CAKComplexR-HSA-69221 (Reactome)
CCNA R-HSA-75202 (Reactome)
CCNA1 ProteinP78396 (Uniprot-TrEMBL)
CCNA2 ProteinP20248 (Uniprot-TrEMBL)
CCNAComplexR-HSA-75202 (Reactome)
CCNB1 ProteinP14635 (Uniprot-TrEMBL)
CCND1 ProteinP24385 (Uniprot-TrEMBL)
CCND2 ProteinP30279 (Uniprot-TrEMBL)
CCND3 ProteinP30281 (Uniprot-TrEMBL)
CCNE1 ProteinP24864 (Uniprot-TrEMBL)
CCNE1:CDK2ComplexR-HSA-68378 (Reactome)
CCNE1:p-CDK2ComplexR-HSA-68371 (Reactome)
CCNE2 ProteinO96020 (Uniprot-TrEMBL)
CCNE2:CDK2ComplexR-HSA-68368 (Reactome)
CCNE2:p-CDK2ComplexR-HSA-68372 (Reactome)
CCNE:CDK2ComplexR-HSA-68374 (Reactome)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CDC25A ProteinP30304 (Uniprot-TrEMBL)
CDC25AProteinP30304 (Uniprot-TrEMBL)
CDC45 ProteinO75419 (Uniprot-TrEMBL)
CDC45ProteinO75419 (Uniprot-TrEMBL)
CDC6 ProteinQ99741 (Uniprot-TrEMBL)
CDC6ProteinQ99741 (Uniprot-TrEMBL)
CDC7 ProteinO00311 (Uniprot-TrEMBL)
CDK1 ProteinP06493 (Uniprot-TrEMBL)
CDK1ProteinP06493 (Uniprot-TrEMBL)
CDK2 ProteinP24941 (Uniprot-TrEMBL)
CDK2ProteinP24941 (Uniprot-TrEMBL)
CDK4 ProteinP11802 (Uniprot-TrEMBL)
CDK4,CDK6:INK4AComplexR-HSA-182579 (Reactome)
CDK4,CDK6ComplexR-HSA-182699 (Reactome)
CDK4,CDK6ComplexR-HSA-69209 (Reactome)
CDK6 ProteinQ00534 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4		ComplexR-HSA-68568 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45		ComplexR-HSA-68564 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex		ComplexR-HSA-68561 (Reactome)
CDKN1A ProteinP38936 (Uniprot-TrEMBL)
CDKN1A,CDKN1BComplexR-HSA-182504 (Reactome)
CDKN1A,CDKN1BComplexR-HSA-182558 (Reactome)
CDKN1AProteinP38936 (Uniprot-TrEMBL)
CDKN1B ProteinP46527 (Uniprot-TrEMBL)
CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ComplexR-HSA-8848419 (Reactome)
CDKN1BProteinP46527 (Uniprot-TrEMBL)
CDKN2B ProteinP42772 (Uniprot-TrEMBL)
CDKN2C ProteinP42773 (Uniprot-TrEMBL)
CDKN2D ProteinP55273 (Uniprot-TrEMBL)
CDKComplexR-HSA-68380 (Reactome)
CDT1 ProteinQ9H211 (Uniprot-TrEMBL)
CDT1ProteinQ9H211 (Uniprot-TrEMBL)
CKS1B ProteinP61024 (Uniprot-TrEMBL)
CKS1BProteinP61024 (Uniprot-TrEMBL)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
CUL1:SKP1:SKP2:CKS1BComplexR-HSA-187547 (Reactome)
CUL1:SKP1:SKP2ComplexR-HSA-187541 (Reactome)
Cyclin

B:CDK1:ORC:origin

of replication		ComplexR-HSA-113637 (Reactome)
Cyclin D:CDK4,CDK6:CDKN1A,CDKN1BComplexR-HSA-141298 (Reactome)
Cyclin D:CDK4,CDK6:CDKN1A,CDKN1BComplexR-HSA-69210 (Reactome)
Cyclin D:p-CDK4,p-CDK6:CDKN1A,CDKN1BComplexR-HSA-69212 (Reactome)
Cyclin E/A:CDK2:CDKN1A,CDKN1BComplexR-HSA-187516 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinComplexR-HSA-187568 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BComplexR-HSA-187565 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1BComplexR-HSA-187522 (Reactome)
Cyclin E:CDK2:CDKN1A,CDKN1BComplexR-HSA-68376 (Reactome)
Cyclin E:p-T160-CDK2:RB1ComplexR-HSA-188373 (Reactome)
Cyclin E:p-T160-CDK2:p-RB1ComplexR-HSA-188391 (Reactome)
Cyclin B:CDK1ComplexR-HSA-75032 (Reactome)
Cyclin DComplexR-HSA-182700 (Reactome)
Cyclin E R-HSA-187493 (Reactome)
Cyclin E/A:CDK2ComplexR-HSA-187496 (Reactome)
Cyclin E:CDK2ComplexR-HSA-157594 (Reactome)
Cyclin E:p-CDK2ComplexR-HSA-68377 (Reactome)
Cyclin E:p-T160-CDK2ComplexR-HSA-188362 (Reactome)
Cyclin EComplexR-HSA-157462 (Reactome)
DBF4 ProteinQ9UBU7 (Uniprot-TrEMBL)
DDKComplexR-HSA-68388 (Reactome)
DHFR ProteinP00374 (Uniprot-TrEMBL)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex		ComplexR-HSA-68510 (Reactome)
DNA polymerase alpha:primaseComplexR-HSA-68507 (Reactome)
DNA polymerase

epsilon:origin

complex		ComplexR-HSA-68485 (Reactome)
DNA polymerase epsilonComplexR-HSA-68483 (Reactome)
DNA primer R-NUL-68424 (Reactome)
DREAM complexComplexR-HSA-1362264 (Reactome)
DYRK1AProteinQ13627 (Uniprot-TrEMBL)
E2F1 ProteinQ01094 (Uniprot-TrEMBL)
E2F1 targetsComplexR-HSA-539110 (Reactome)
E2F1:TFDP1ComplexR-HSA-68653 (Reactome)
E2F1ProteinQ01094 (Uniprot-TrEMBL)
E2F2 ProteinQ14209 (Uniprot-TrEMBL)
E2F3 ProteinO00716 (Uniprot-TrEMBL)
E2F4 ProteinQ16254 (Uniprot-TrEMBL)
E2F4,E2F5:TFDP1,TFDP2ComplexR-HSA-1226072 (Reactome)
E2F4:TFDP1,TFDP2ComplexR-HSA-1362228 (Reactome)
E2F5 ProteinQ15329 (Uniprot-TrEMBL)
FBXO5 ProteinQ9UKT4 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HDAC1 ProteinQ13547 (Uniprot-TrEMBL)
HDAC1:RBL1:E2F4:TFDP1,TFDP2ComplexR-HSA-1227668 (Reactome)
HDAC1:RBL2:E2F4/5:DP1/2ComplexR-HSA-1227666 (Reactome)
HDAC1ProteinQ13547 (Uniprot-TrEMBL)
INK4AComplexR-HSA-182588 (Reactome)
LIN37 ProteinQ96GY3 (Uniprot-TrEMBL)
LIN52 ProteinQ52LA3 (Uniprot-TrEMBL)
LIN54 ProteinQ6MZP7 (Uniprot-TrEMBL)
LIN9 ProteinQ5TKA1 (Uniprot-TrEMBL)
MAX ProteinP61244 (Uniprot-TrEMBL)
MCM10 ProteinQ7L590 (Uniprot-TrEMBL)
MCM10:active

pre-replicative

complex		ComplexR-HSA-156564 (Reactome)
MCM10:pre-replicative complexComplexR-HSA-68560 (Reactome)
MCM10ProteinQ7L590 (Uniprot-TrEMBL)
MCM2 ProteinP49736 (Uniprot-TrEMBL)
MCM2-7ComplexR-HSA-68558 (Reactome)
MCM3 ProteinP25205 (Uniprot-TrEMBL)
MCM4 ProteinP33991 (Uniprot-TrEMBL)
MCM5 ProteinP33992 (Uniprot-TrEMBL)
MCM6 ProteinQ14566 (Uniprot-TrEMBL)
MCM7 ProteinP33993 (Uniprot-TrEMBL)
MCM8 ProteinQ9UJA3 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
MYBL2ProteinP10244 (Uniprot-TrEMBL)
MYC ProteinP01106 (Uniprot-TrEMBL)
MYC:MAXComplexR-HSA-188378 (Reactome)
MuvB complexComplexR-HSA-1362248 (Reactome)
ORC1 ProteinQ13415 (Uniprot-TrEMBL)
ORC2 ProteinQ13416 (Uniprot-TrEMBL)
ORC3 ProteinQ9UBD5 (Uniprot-TrEMBL)
ORC4 ProteinO43929 (Uniprot-TrEMBL)
ORC5 ProteinO43913 (Uniprot-TrEMBL)
ORC6 ProteinQ9Y5N6 (Uniprot-TrEMBL)
ORC:origin of replicationComplexR-HSA-68540 (Reactome)
PCNA ProteinP12004 (Uniprot-TrEMBL)
PCNAProteinP12004 (Uniprot-TrEMBL)
PKMYT1ProteinQ99640 (Uniprot-TrEMBL)
POLA1 ProteinP09884 (Uniprot-TrEMBL)
POLA2 ProteinQ14181 (Uniprot-TrEMBL)
POLE ProteinQ07864 (Uniprot-TrEMBL)
POLE2 ProteinP56282 (Uniprot-TrEMBL)
PP2AComplexR-HSA-1362456 (Reactome)
PP2AComplexR-HSA-1363265 (Reactome)
PPP2CA ProteinP67775 (Uniprot-TrEMBL)
PPP2CB ProteinP62714 (Uniprot-TrEMBL)
PPP2R1A ProteinP30153 (Uniprot-TrEMBL)
PPP2R1B ProteinP30154 (Uniprot-TrEMBL)
PPP2R2A ProteinP63151 (Uniprot-TrEMBL)
PPP2R3B ProteinQ9Y5P8 (Uniprot-TrEMBL)
PRIM1 ProteinP49642 (Uniprot-TrEMBL)
PRIM2 ProteinP49643 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
Pi MetaboliteCHEBI:18367 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
RB1 ProteinP06400 (Uniprot-TrEMBL)
RB1:RNA primer-DNA

primer:origin duplex with DNA

damage		ComplexR-HSA-113646 (Reactome)
RB1:TFDP1:E2F1-3ComplexR-HSA-68644 (Reactome)
RB1ProteinP06400 (Uniprot-TrEMBL)
RBBP4 ProteinQ09028 (Uniprot-TrEMBL)
RBL1 ProteinP28749 (Uniprot-TrEMBL)
RBL1:Cyclin E/A:CDK2ComplexR-HSA-1363310 (Reactome)
RBL1:E2F4:DP1/2:Cyclin E/A:CDK2ComplexR-HSA-1363307 (Reactome)
RBL1:E2F4:TFDP1,TFDP2ComplexR-HSA-1226088 (Reactome)
RBL1ProteinP28749 (Uniprot-TrEMBL)
RBL2 ProteinQ08999 (Uniprot-TrEMBL)
RBL2:Cyclin E/A:CDK2ComplexR-HSA-1363301 (Reactome)
RBL2:E2F4,E2F5:TFDP1,TFDP2ComplexR-HSA-1226089 (Reactome)
RBL2:E2F4/5:DP1/2:Cyclin E/A:CDK2ComplexR-HSA-1363300 (Reactome)
RBL2ProteinQ08999 (Uniprot-TrEMBL)
RNA primer R-NUL-68422 (Reactome)
RNA primer-DNA

primer:origin duplex with DNA

damage		ComplexR-ALL-113656 (Reactome)
RNA primer-DNA

primer:origin

duplex		ComplexR-HSA-68425 (Reactome)
RNA primer:origin duplex with DNA damage R-NUL-113499 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA1-4ComplexR-HSA-68567 (Reactome)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPA4 ProteinQ13156 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
RRM2 ProteinP31350 (Uniprot-TrEMBL)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SKP2 ProteinQ13309 (Uniprot-TrEMBL)
TFDP1 ProteinQ14186 (Uniprot-TrEMBL)
TFDP1:E2F1-3ComplexR-HSA-1227905 (Reactome)
TFDP2 ProteinQ14188 (Uniprot-TrEMBL)
TK2 ProteinO00142 (Uniprot-TrEMBL)
TOP2AProteinP11388 (Uniprot-TrEMBL)
TYMS ProteinP04818 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-p-T401,S672,1035-RBL2ComplexR-HSA-1363324 (Reactome)
UbiquitinComplexR-HSA-68524 (Reactome)
WEE1ProteinP30291 (Uniprot-TrEMBL)
cyclin R-HSA-68379 (Reactome)
origin of replicationR-NUL-68419 (Reactome)
origin of replication R-NUL-68419 (Reactome)
p-CDK2 ProteinP24941 (Uniprot-TrEMBL)
p-MCM2-7ComplexR-HSA-68569 (Reactome)
p-MuvB complexComplexR-HSA-1362259 (Reactome)
p-RB1 ProteinP06400 (Uniprot-TrEMBL) The pRB C-terminus contains a cluster of seven candidate in vivo cdk phosphorylation sites (residues 795, 807, 811, 821, and 826) and is phosphorylated in vitro by cyclin A, cyclin E, and cyclin D-associated kinases.
p-S130-CDKN1A ProteinP38936 (Uniprot-TrEMBL)
p-S28-LIN52 ProteinQ52LA3 (Uniprot-TrEMBL)
p-S795-RB1ProteinP06400 (Uniprot-TrEMBL)
p-T160-CDK2 ProteinP24941 (Uniprot-TrEMBL)
p-T172-CDK4 ProteinP11802 (Uniprot-TrEMBL)
p-T177-CDK6 ProteinQ00534 (Uniprot-TrEMBL)
p-T187-CDKN1B ProteinP46527 (Uniprot-TrEMBL)
p-T369,S640,S964,S975-RBL1ProteinP28749 (Uniprot-TrEMBL)
p-T401,S672,1035-RBL2:SCF(Skp2):Cks1ComplexR-HSA-1363326 (Reactome)
p-T401,S672,S1035-RBL2 ProteinQ08999 (Uniprot-TrEMBL)
p-T401,S672,S1035-RBL2ProteinQ08999 (Uniprot-TrEMBL)
p-Y342-PTK6 ProteinQ13882 (Uniprot-TrEMBL)
p-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ComplexR-HSA-8848415 (Reactome)
p-Y342-PTK6ProteinQ13882 (Uniprot-TrEMBL)
p-Y88-CDKN1B ProteinP46527 (Uniprot-TrEMBL)
p-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ComplexR-HSA-8848441 (Reactome)
p16-INK4a ProteinP42771 (Uniprot-TrEMBL)
pre-replicative complexComplexR-HSA-68559 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-187574 (Reactome)
ADPArrowR-HSA-1226094 (Reactome)
ADPArrowR-HSA-1226095 (Reactome)
ADPArrowR-HSA-1362270 (Reactome)
ADPArrowR-HSA-187520 (Reactome)
ADPArrowR-HSA-188350 (Reactome)
ADPArrowR-HSA-188390 (Reactome)
ADPArrowR-HSA-68954 (Reactome)
ADPArrowR-HSA-69195 (Reactome)
ADPArrowR-HSA-69213 (Reactome)
ADPArrowR-HSA-69223 (Reactome)
ADPArrowR-HSA-69227 (Reactome)
ADPArrowR-HSA-69690 (Reactome)
ADPArrowR-HSA-69691 (Reactome)
ADPArrowR-HSA-8848436 (Reactome)
ATPR-HSA-1226094 (Reactome)
ATPR-HSA-1226095 (Reactome)
ATPR-HSA-1362270 (Reactome)
ATPR-HSA-187520 (Reactome)
ATPR-HSA-188350 (Reactome)
ATPR-HSA-188390 (Reactome)
ATPR-HSA-68954 (Reactome)
ATPR-HSA-69195 (Reactome)
ATPR-HSA-69213 (Reactome)
ATPR-HSA-69223 (Reactome)
ATPR-HSA-69227 (Reactome)
ATPR-HSA-69690 (Reactome)
ATPR-HSA-69691 (Reactome)
ATPR-HSA-8848436 (Reactome)
Aborted replication complexArrowR-HSA-113643 (Reactome)
CAKmim-catalysisR-HSA-188350 (Reactome)
CAKmim-catalysisR-HSA-69223 (Reactome)
CCNAArrowR-HSA-1362300 (Reactome)
CCNE1:CDK2R-HSA-69690 (Reactome)
CCNE1:p-CDK2ArrowR-HSA-69690 (Reactome)
CCNE2:CDK2R-HSA-69691 (Reactome)
CCNE2:p-CDK2ArrowR-HSA-69691 (Reactome)
CCNE:CDK2ArrowR-HSA-157906 (Reactome)
CCNE:CDK2ArrowR-HSA-69199 (Reactome)
CCNE:CDK2R-HSA-188350 (Reactome)
CCNE:CDK2R-HSA-69195 (Reactome)
CCNE:CDK2R-HSA-69562 (Reactome)
CDC25AArrowR-HSA-113505 (Reactome)
CDC25AArrowR-HSA-1362277 (Reactome)
CDC25AArrowR-HSA-188345 (Reactome)
CDC25Amim-catalysisR-HSA-69199 (Reactome)
CDC45R-HSA-68917 (Reactome)
CDC6ArrowR-HSA-1362277 (Reactome)
CDK1ArrowR-HSA-1362300 (Reactome)
CDK2R-HSA-69191 (Reactome)
CDK4,CDK6:INK4AArrowR-HSA-182594 (Reactome)
CDK4,CDK6:INK4ATBarR-HSA-69213 (Reactome)
CDK4,CDK6R-HSA-182594 (Reactome)
CDK4,CDK6R-HSA-69213 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4		ArrowR-HSA-68914 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4		ArrowR-HSA-68916 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45:RPA1-4		ArrowR-HSA-68960 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45		ArrowR-HSA-68917 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex:CDC45		R-HSA-68916 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex		ArrowR-HSA-68918 (Reactome)
CDK:DDK:MCM10:active

pre-replicative

complex		R-HSA-68917 (Reactome)
CDKN1A,CDKN1BR-HSA-69213 (Reactome)
CDKN1A,CDKN1BR-HSA-69562 (Reactome)
CDKN1A,CDKN1Bmim-catalysisR-HSA-69562 (Reactome)
CDKN1AArrowR-HSA-187828 (Reactome)
CDKN1AR-HSA-187828 (Reactome)
CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))R-HSA-8848414 (Reactome)
CDKN1BArrowR-HSA-187506 (Reactome)
CDKN1BR-HSA-187506 (Reactome)
CDKR-HSA-68918 (Reactome)
CDT1ArrowR-HSA-68940 (Reactome)
CKS1BR-HSA-187545 (Reactome)
CUL1:SKP1:SKP2:CKS1BArrowR-HSA-1363331 (Reactome)
CUL1:SKP1:SKP2:CKS1BArrowR-HSA-187545 (Reactome)
CUL1:SKP1:SKP2:CKS1BArrowR-HSA-187574 (Reactome)
CUL1:SKP1:SKP2:CKS1BR-HSA-1363328 (Reactome)
CUL1:SKP1:SKP2:CKS1BR-HSA-187552 (Reactome)
CUL1:SKP1:SKP2R-HSA-187545 (Reactome)
Cyclin

B:CDK1:ORC:origin

of replication		ArrowR-HSA-113638 (Reactome)
Cyclin D:CDK4,CDK6:CDKN1A,CDKN1BArrowR-HSA-141299 (Reactome)
Cyclin D:CDK4,CDK6:CDKN1A,CDKN1BArrowR-HSA-69213 (Reactome)
Cyclin D:CDK4,CDK6:CDKN1A,CDKN1BR-HSA-141299 (Reactome)
Cyclin D:CDK4,CDK6:CDKN1A,CDKN1BR-HSA-69223 (Reactome)
Cyclin D:p-CDK4,p-CDK6:CDKN1A,CDKN1BArrowR-HSA-69223 (Reactome)
Cyclin D:p-CDK4,p-CDK6:CDKN1A,CDKN1Bmim-catalysisR-HSA-1226094 (Reactome)
Cyclin D:p-CDK4,p-CDK6:CDKN1A,CDKN1Bmim-catalysisR-HSA-1226095 (Reactome)
Cyclin D:p-CDK4,p-CDK6:CDKN1A,CDKN1Bmim-catalysisR-HSA-69227 (Reactome)
Cyclin E/A:CDK2:CDKN1A,CDKN1BR-HSA-187520 (Reactome)
Cyclin E/A:CDK2:CDKN1A,CDKN1Bmim-catalysisR-HSA-187520 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinArrowR-HSA-187575 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinR-HSA-187574 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinmim-catalysisR-HSA-187575 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BArrowR-HSA-187552 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BR-HSA-187575 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1BArrowR-HSA-187520 (Reactome)
Cyclin E/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1BR-HSA-187552 (Reactome)
Cyclin E:CDK2:CDKN1A,CDKN1BArrowR-HSA-69562 (Reactome)
Cyclin E:p-T160-CDK2:RB1ArrowR-HSA-188386 (Reactome)
Cyclin E:p-T160-CDK2:RB1R-HSA-188390 (Reactome)
Cyclin E:p-T160-CDK2:RB1mim-catalysisR-HSA-188390 (Reactome)
Cyclin E:p-T160-CDK2:p-RB1ArrowR-HSA-188390 (Reactome)
Cyclin B:CDK1ArrowR-HSA-113505 (Reactome)
Cyclin B:CDK1R-HSA-113638 (Reactome)
Cyclin DR-HSA-69213 (Reactome)
Cyclin E/A:CDK2ArrowR-HSA-187574 (Reactome)
Cyclin E/A:CDK2R-HSA-1363303 (Reactome)
Cyclin E/A:CDK2R-HSA-1363306 (Reactome)
Cyclin E/A:CDK2R-HSA-1363311 (Reactome)
Cyclin E/A:CDK2R-HSA-1363314 (Reactome)
Cyclin E:CDK2ArrowR-HSA-69191 (Reactome)
Cyclin E:CDK2R-HSA-157906 (Reactome)
Cyclin E:p-CDK2ArrowR-HSA-69195 (Reactome)
Cyclin E:p-CDK2R-HSA-69199 (Reactome)
Cyclin E:p-T160-CDK2ArrowR-HSA-188350 (Reactome)
Cyclin E:p-T160-CDK2R-HSA-188386 (Reactome)
Cyclin ER-HSA-69191 (Reactome)
DDKR-HSA-68918 (Reactome)
DDKmim-catalysisR-HSA-68954 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase alpha:origin

complex		ArrowR-HSA-68914 (Reactome)
DNA polymerase alpha:primaseArrowR-HSA-113504 (Reactome)
DNA polymerase alpha:primaseR-HSA-68914 (Reactome)
DNA polymerase

epsilon:origin

complex		ArrowR-HSA-68960 (Reactome)
DNA polymerase

epsilon:origin

complex		R-HSA-68914 (Reactome)
DNA polymerase epsilonR-HSA-68960 (Reactome)
DREAM complexArrowR-HSA-1362261 (Reactome)
DREAM complexTBarR-HSA-1362277 (Reactome)
DYRK1Amim-catalysisR-HSA-1362270 (Reactome)
E2F1 targetsArrowR-HSA-539107 (Reactome)
E2F1:TFDP1ArrowR-HSA-539107 (Reactome)
E2F1:TFDP1R-HSA-113643 (Reactome)
E2F1ArrowR-HSA-1362277 (Reactome)
E2F1ArrowR-HSA-1362300 (Reactome)
E2F4,E2F5:TFDP1,TFDP2ArrowR-HSA-1226094 (Reactome)
E2F4:TFDP1,TFDP2ArrowR-HSA-1226095 (Reactome)
H2OR-HSA-1363274 (Reactome)
H2OR-HSA-1363276 (Reactome)
H2OR-HSA-69199 (Reactome)
HDAC1:RBL1:E2F4:TFDP1,TFDP2ArrowR-HSA-1227671 (Reactome)
HDAC1:RBL1:E2F4:TFDP1,TFDP2TBarR-HSA-1362300 (Reactome)
HDAC1:RBL2:E2F4/5:DP1/2ArrowR-HSA-1227670 (Reactome)
HDAC1:RBL2:E2F4/5:DP1/2TBarR-HSA-1362300 (Reactome)
HDAC1R-HSA-1227670 (Reactome)
HDAC1R-HSA-1227671 (Reactome)
INK4AR-HSA-182594 (Reactome)
MCM10:active

pre-replicative

complex		ArrowR-HSA-68940 (Reactome)
MCM10:active

pre-replicative

complex		R-HSA-68918 (Reactome)
MCM10:pre-replicative complexArrowR-HSA-68919 (Reactome)
MCM10:pre-replicative complexR-HSA-68940 (Reactome)
MCM10R-HSA-68919 (Reactome)
MCM2-7R-HSA-68954 (Reactome)
MYBL2ArrowR-HSA-1362300 (Reactome)
MYC:MAXArrowR-HSA-188345 (Reactome)
MuvB complexR-HSA-1362270 (Reactome)
ORC:origin of replicationR-HSA-113638 (Reactome)
PCNAArrowR-HSA-1362277 (Reactome)
PKMYT1mim-catalysisR-HSA-69690 (Reactome)
PKMYT1mim-catalysisR-HSA-69691 (Reactome)
PP2Amim-catalysisR-HSA-113503 (Reactome)
PP2Amim-catalysisR-HSA-1363274 (Reactome)
PP2Amim-catalysisR-HSA-1363276 (Reactome)
PiArrowR-HSA-1363274 (Reactome)
PiArrowR-HSA-1363276 (Reactome)
PiArrowR-HSA-69199 (Reactome)
R-HSA-113503 (Reactome) At the beginning of this reaction, 1 molecule of 'phospho-Retinoblastoma protein', and 1 molecule of 'RNA primer-DNA primer:origin duplex with DNA damage' are present. At the end of this reaction, 1 molecule of 'Rb1:RNA primer-DNA primer:origin duplex with DNA damage' is present.

This reaction takes place in the 'nucleus' and is mediated by the 'phosphoprotein phosphatase activity' of 'PP2A'.

R-HSA-113504 (Reactome) At the beginning of this reaction, 1 molecule of 'RNA primer-DNA primer:origin duplex' is present. At the end of this reaction, 1 molecule of 'DNA polymerase alpha:primase', and 1 molecule of 'RNA primer-DNA primer:origin duplex with DNA damage' are present.

This reaction takes place in the 'nucleus'.

R-HSA-113505 (Reactome) At the end of this reaction, 1 molecule of 'Cyclin B:Cdk1 complex', and 1 molecule of 'Cdc25A' are present.

This reaction takes place in the 'nucleus'.

R-HSA-113638 (Reactome) This event is inferred from the fission yeast. Cyclin B activity is thought to inhibit pre-RC formation by first associating with ORC during DNA replication.
R-HSA-113643 (Reactome) This set of events is inferred from annotated events in Drosophila.

Rb1 is normally hyperphosphorylated by CycD/CDK4/CDK6 and Cyclin E/CDK2 for transition into S-phase. PP2A can then reverse this reaction, in this case, in response to DNA damage induced checkpoint.
R-HSA-1226094 (Reactome) At G1 entry from G0, p130 (RBL2) is phosphorylated on three threonine and serine residues by cyclin D1 dependent kinases CDK4 and/or CDK6, leading to dissociation of p130 (RBL2) from complexes it formed with E2F4 or E2F5 and DP1 or DP2. This is thought to promote translocation of E2F4 and E2F5, which lack nuclear localization signals, to the cytosol, allowing activating E2Fs (E2F1, E2F2 and E2F3) to bind E2F promoters and activate transcription of genes needed for G1 progression.
R-HSA-1226095 (Reactome) In late G1, cyclin D dependent kinases CDK4 and CDK6 phosphorylate RBL1 (p107) on four serine and threonine residues (S964, S975, T369 and S640), leading to dissociation of phosphorylated RBL1 (p107) from E2F4 in complex with either DP-1 or DP-2. E2F4, which lacks nuclear localization signal, is then thought to translocate to the cytosol, allowing E2F promoter sites to become occupied by activating E2Fs (E2F1, E2F2, and E2F3), resulting in transcription of E2F targets needed for cell cycle progression.
R-HSA-1227670 (Reactome) p130 (RBL2) in complex with E2F4 or E2F5 and DP1 or DP2 recruits histone deacetylase HDAC1, probably in complex with other chromatin modification factors, and represses transcription of E2F target promoters during G0 in quiescent cells.
R-HSA-1227671 (Reactome) p107 (RBL1) in complex with E2F4 and DP1 or DP2 recruits histone deacetylase HDAC1 (possibly in complex with other chromatin modification proteins) through LXCXE-like motif, shared by pocket proteins, to repress transcription of E2F target genes in early G1.
R-HSA-1362261 (Reactome) In G0 and early G1, p130 (RBL2) bound to E2F4 or E2F5 and DP1 or DP2 associates with the MuvB complex, consisting of LIN9, LIN37, LIN52, LIN54 and RBBP4 to form evolutionarily conserved DREAM complex. Phosphorylation of LIN52 on serine residue S28 is critical for association of MuvB complex with p130 (RBL2).
R-HSA-1362270 (Reactome) LIN52 subunit of MuvB complex is phosphorylated by the protein kinase DYRK1A on the serine residue S28, promoting association of MuvB with p130 (RBL2). From model organism studies, DYRK proteins are known to function in cell cycle regulation, differentiation and stress response.
R-HSA-1362277 (Reactome) DREAM complex is evolutionarily conserved and is reponsible for transcriptional repressession of cell cycle-regulated genes in G0 and early G1.
R-HSA-1362300 (Reactome) In G0 and early G1, expression of E2F target genes such as Cyclin A, E2F1, CDC2 and MYBL2 is inhibited by complexes containing p130 (RBL2) and p107 (RBL1), respectively, and histone deacetylase HDAC1.
R-HSA-1363274 (Reactome) Dephosphorylation of p107 (RBL1) by PP2A complex containing either PPP2R3B (B" beta) or PPP2R2A (B alpha) regulatory subunit plays a role in maintaining the equilibrium of hyperphosphorylated and hypophosphorylated p107 (RBL1), through counteracting action of cyclin dependent kinases (CDKs) throughout the cell cycle. It is assumed that PP2A dephosphorylates p107 (RBL1) on all four phosphorylation sites, but further experiments are needed to confirm this.
R-HSA-1363276 (Reactome) Dephosphorylation of p130 (RBL2) by PP2A complex containing either PPP2R3B (B" beta) or PPP2R2A (B alpha) regulatory subunit plays a role in maintaining the equilibrium of hyperphosphorylated and hypophosphorylated p130 (RBL2), through counteracting action of cyclin dependent kinases (CDKs). It is assumed that PP2A dephosphorylates p130 (RBL2) on all three phosphorylation sites, but further experiments are needed to confirm this.
R-HSA-1363303 (Reactome) p130 (RBL2) in complex with E2F4/5 and DP1/2 binds to cyclin A or cyclin E in complex with CDK2 through its conserved LFG pocket domain motif and amino terminus, leading to inhibition of CDK2 kinase activity and suppression of cellular growth.
R-HSA-1363306 (Reactome) p130 (RBL2) is able to bind complexes of CDK2 with either cyclin A or cyclin E through the cyclin-binding LFG motif within the pocket domain, which is conserved in p107 (RBL1) and p21/WAF1/Cip1 family of cyclin-dependent kinases. In addition to LFG motif, amino terminal region of p130 (RBL2), conserved in p107 (RBL1), is necessary for inhibition of CDK2 kinase activity. Presence of E2F is not required for this interaction.
R-HSA-1363311 (Reactome) p107 (RBL1) in complex with E2F4 and DP1/2 binds to cyclin A or cyclin E in complex with CDK2 through its conserved LFG pocket domain motif and amino terminus, leading to inhibition of CDK2 kinase activity and suppression of cellular growth.
R-HSA-1363314 (Reactome) p107 (RBL1) is able to bind complexes of CDK2 with either cyclin A or cyclin E, through cyclin-binding LFG motif in the pocket domain, which is conserved in p130 (RBL2) and p21/WAF1/Cip1 family of cyclin-dependent kinase inhibitors. In addition to the LFG motif, the amino terminal sequence conserved in the p107 (RBL1) and p130 (RBL2) is needed for inhibition of CDK2 kinase activity. Presence of E2F is not required for this interaction.
R-HSA-1363328 (Reactome) Phosphorylated p130 (RBL2) binds SCF (Skp2) ubiquitin ligase in complex with Cks1. Phosphorylation of p130 (RBL2) serine residue S672 by CDK4/6 is critical for this interaction.
R-HSA-1363331 (Reactome) As quiescent G0 cells reenter the cell cycle, p130 (RBL2) is phosphorylated by CDK4/6. This phosphorylated p130 (RBL2) binds ubiquitin ligase SCF (Skp2) in complex with Cks1, and is subsequently ubiquitinated and degraded similarly to p27, which is another target of SCF (Skp2).
R-HSA-141299 (Reactome) Cyclin D:CDK4/6 complexes translocate to the nucleus from the cytoplasm, and this nuclear accumulation is directed by p21/p27 (LaBaer et al. 1997).
R-HSA-157906 (Reactome) Follow their formation, the Cyclin E:Cdk2 complexes are translocated to the nucleus.
R-HSA-182594 (Reactome) Prior to mitogen activation, the inhibitory proteins, INK4 (p15, p16, p18, and p19) associate with the catalytic domain of free CDK4/6, preventing its association with cyclins, and thus its activation.
R-HSA-187506 (Reactome) p27 translocates to the nucleoplasm where it associates with CyclinE:Cdk2 complexes. Localization of p27 to the nucleus is necessary to inhibit Cdk activation by Cdk-activating kinase.
R-HSA-187520 (Reactome) The interaction between the Skp2 subunit of the SCF(Skp2) complex and p27 is dependent upon Cdk2:Cyclin A/E mediated phosphorylation of p27 at Thr 187 (Carrano et al, 1999; Tsvetkov et al, 1999). There is evidence that Cyclin A/B:Cdk1 can also bind and phosphorylate p27 on Thr 187 (Nakayama et al., 2004). This phosphorylation is also essential for the subsequent ubiquitination of p27.
R-HSA-187545 (Reactome) The accessory protein, Cks1 promotes efficient interaction between phosphorylated p27 and the SCF (Skp2) complex (Ganoth et al., 2001; Spruck et al., 2001). Cks1 binds to Skp2 in the leucine-rich repeat (LRR) domain and C-terminal tail (Hao et al., 2005). The phosphorylated Thr187 side chain of p27 associates with a phosphate binding site on Cks1, and the side chain containing Glu185 is positioned in the interface between Skp2 and Cks1 where it interacts with both (Hao et al., 2005).
R-HSA-187552 (Reactome) The association of Cks1 with both Skp2 and phosphorylated p27 promotes a tight interaction between p27 and the SCF complex (Hao et al., 2005).
R-HSA-187574 (Reactome) Following ubiquitination by the SCF(Skp2):Cks1 complex, phospho-p27/p21 is degraded by the 26S proteasome.
R-HSA-187575 (Reactome) Once in tight contact with the SCF (Skp2):Cks1 complex, phosphorylated p27/p21 is ubiquitinated.
R-HSA-187828 (Reactome) p21 associates with and inhibits Cyclin:Cdk complexes in the nucleus.
R-HSA-188345 (Reactome) The Myc/Max heterodimer binds to elements in the cdc25A gene and activates transcription in mid to late G1.
R-HSA-188350 (Reactome) Phosphorylation of cyclin-dependent kinases (CDKs) by the CDK-activating kinase (CAK) is required for the activation of the CDK kinase activity. The association of p21/p27 with the Cyclin A/E:Cdk2 complex prevents CAK mediated phosphorylation of Cdk2 (Aprelikova et al., 1995).
R-HSA-188386 (Reactome) pRB contains, in its C terminus, a cyclin-cdk interaction motif like that found in E2F1 and p21 that enables it to be recognized and phosphorylated by cyclin-cdk complexes.
R-HSA-188390 (Reactome) Cyclin E forms a complex with cdk2 and collaborates with the cyclin D-dependent kinases in phosphorylating Rb.
R-HSA-539107 (Reactome) E2F1 binds to E2F binding sites on the genome activating the synthesis of the target proteins. For annotation purposes, the reactions regulated by E2F1 are grouped under this pathway and information about the target genes alone are displayed for annotation purposes.
Cellular targets for activation by E2F1 include thymidylate synthetase, Rir2, Dihydrofolate reductase, Cdc2, Cyclin A1, Cdc6 (DeGregori et al., 1995), Cdt1 (Yoshida and Inoue, 2004), CDC45 (Arata et al., 2000), CDC6 (Yan et al., 1998; Ohtani et al., 1998), Cyclin E (Ohtani et al., 1996), Emi1 (Hsu et al., 2002), and Orc1 (Ohtani et al., 1997). The activation of TK2 (Dnk1) and Cdc25A by E2F1 have been inferred from similar events in Drosophila (Duronio and O'Farrell, 1994;Reis and Edgar, 2004).
Rir2 protein is involved in dNTP level regulation and activation of this enzyme results in higher levels of dNTPs in anticipation of S-phase. E2F activation of Rir2 has been shown also in Drosophila by Duronio and O'Farrell (1994). E2F1 activation of CDC45 is shown in mouse cells by using human E2F1 construct (Arata et al., 2000). Cyclin E is also transcriptionally regulated by E2F1. Cyclin E protein plays important role in the transition of G1 in S-phase by associating with Cdk2 (Ohtani et al., 1996). E2F activation of PCNA has been demonstrated in Drosophila (DeGregori et al., 1995) and in some human cells by using recombinant adenovirus constructs. E2F activation of Polymerase A (Pol A) has been demonstrated in some human cells. It has also been demonstrated in Drosophila by Ohtani and Nevins (1994). It has been observed in Drosophila that E2F1 regulated expression of Orc1 stimulates ORC1-6 complex formation and binding to the origin of replication (Asano and Wharton, 1999). Orc1-6 recruit Cdc6 and Cdt1 that are required to recruit the MCM2-7 replication helicases. E2F1 regulation incorporates a feedback mechanism where in Geminin can inhibit MCM2-7 recruitment of ORC1-6 complex by interacting with Cdc6/Cdt1. The activation of Cdc25A and TK2 (Dnk1) by E2F1 has been inferred from similar events in Drosophila (Duronio RJ, O'Farrell 1994; Reis and Edgar, 2004). E2F1 activates string (Cdc25) that in turn activates Cyclin B/Cdk1. A similar phenomenon has been observed in mouse NIH 3T3 cells and in Rat1 cells.
R-HSA-68914 (Reactome) DNA polymerase alpha:primase is comprised of four subunits, p180, p70, p58, and p49. The two primase subunits, p58 and p49, form a tight complex. The p49 subunit contains the DNA primase activity and one role of p58 appears to be tethering p49 to p180, the DNA polymerase catalytic subunit. The fourth subunit, p70, binds p180 and may tether the DNA polymerase alpha:primase complex to Cdc45.
R-HSA-68916 (Reactome) After pre-RC assembly and Cdc45 association with the origin of replication, Replication Protein A (RPA) also associates with chromatin. RPA is a heterotrimeric complex containing p70, p34, and p11 subunits, and also is required for DNA recombination and DNA repair. The p70 subunit of RPA binds to the primase subunits of Pol alpha:primase. The p70 and p34 subunits of RPA are phosphorylated in a cell cycle-dependent manner. RPA is a single-strand DNA (ssDNA) binding protein and its association with chromatin at this stage suggests that DNA is partially unwound. This suggestion has been confirmed by detection of ssDNA in budding yeast origins of replication using chemical methods.
R-HSA-68917 (Reactome) Once the Mcm2-7 complex has been assembled onto the origin of replication, the next step is the assembly of Cdc45, an essential replication protein, in late G1. The assembly of Cdc45 onto origins of replication forms a complex distinct from the pre-replicative complex, sometimes called the pre-initiation complex. The assembly of Cdc45 onto origins correlates with the time of initiation. Like the Mcm2-7 proteins, Cdc45 binds specifically to origins in the G1 phase of the cell cycle and then to non-origin DNA during S phase and is therefore thought to travel with the replication fork. Indeed, S. cerevisiae Cdc45 is required for DNA replication elongation as well as replication initiation. Cdc45 is required for the association of alpha DNA polymerase:primase with chromatin. Based on this observation and the observation that in S. cerevisiae, cCdc45 has been found in large complexes with some components of Mcm2-7 complex, it has been suggested that Cdc45 plays a scaffolding role at the replication fork, coupling Pol-alpha:primase to the replication fork through the helicase. Association of Cdc45 with origin DNA is regulated in the cell cycle and its association is dependent on the activity of cyclin-dependent kinases but not the Cdc7/Dbf4 kinase. In Xenopus egg extracts, association of Cdc45 with chromatin is dependent on Xmus101. TopBP1, the human homolog of Xmus1, is essential for DNA replication and interacts with DNA polymerase epsilon, one of the polymerases involved in replicating the genome. TopBP1 homologs have been found in S. cerevisiae and S. pombe. Sld3, an additional protein required for Cdc45 association with chromatin in S. cerevisiae and S. pombe, has no known human homolog.
R-HSA-68918 (Reactome) At the beginning of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', 1 molecule of 'DDK', and 1 molecule of 'CDK' are present. At the end of this reaction, 1 molecule of 'CDK:DDK:Mcm10:pre-replicative complex' is present.

This reaction takes place in the 'nucleus'.

R-HSA-68919 (Reactome) MCM10 is required for human DNA replication. In S. cerevisiae, Mcm10, like Mcm2-7, is required for minichromosome maintenance, but Mcm10 has no sequence homology with these other proteins (Merchant et al., 1997). Genetic studies have demonstrated that Mcm10 is required for DNA replication in S. pombe (Aves et al., 1998) and S. cerevisiae cells (Homesley et al., 2000) and immunodepletion of XlMcm10 interferes with DNA replication in Xenopus egg extracts (Wohlschlegel et al., 2002). Human Mcm10 interacts with chromatin in G1 phase and then dissociates during G2 phase. In S. cerevisiae, Mcm10 has been shown to localize to origins during G1 (Ricke and Bielinsky, 2004), and it may stabilize the association of Mcm2-7 with the pre-replicative complex (Sawyer et al., 2004). This timing of association is consistent with studies that demonstrate that, in Xenopus egg extracts, Mcm10 is required for association of Cdc45, but not Mcm2-7 with chromatin. Biochemical evidence that Mcm10 plays a direct role in the activation of the pre-replicative complex includes the requirement for SpMcm10 in the phosphorylation of the Mcm2-7 complex by DDK (Lee et al., 2004) and the fact that SpMcm10 binds and stimulates DNA polymerase alpha activity (Fien et al., 2004).
R-HSA-68940 (Reactome) At the beginning of this reaction, 1 molecule of 'Mcm10:pre-replicative complex' is present. At the end of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', and 1 molecule of 'CDT1' are present.

This reaction takes place in the 'nucleus'.

R-HSA-68954 (Reactome) At the beginning of this reaction, 1 molecule of 'Mcm2-7 complex', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'phosphorylated Mcm2-7 complex', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'DDK'.

R-HSA-68960 (Reactome) At the beginning of this reaction, 1 molecule of 'origin of replication', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon:origin complex' is present.



R-HSA-69191 (Reactome) The E-type cyclins and Cyclin Dependent Kinase 2 control the transition from G1 to S phase. Cdk2 is competent to carry out the necessary reactions only when complexed with Cyclin E.
R-HSA-69195 (Reactome) Wee1 phosphorylates Cdk2, inhibiting entry into S-phase (Watanabe et al., 1995; Wu et al., 2001).
R-HSA-69199 (Reactome) Cdc25A dephosphorylates Cdk2 and activates cyclin E-Cdk2 and cyclin A-Cdk2 kinases (Blomberg and Hoffmann, 1999).
R-HSA-69213 (Reactome) The formation of CyclinD:CDK4/6 complexes is promoted by two proteins, p21Cip1/Waf1 and p27kip1. Activity of the cyclin-dependent kinases 4 and 6 can be inhibited by the binding of several small CDK-inhibitory proteins (CKIs).
R-HSA-69223 (Reactome) Phosphorylation of CDK4 on Thr172 depends on prior D-type cyclin binding (Bockstaele et al., 2006).
R-HSA-69227 (Reactome) Cyclin D:Cdk4 mediated phosphorylation of RB1 releases RB1 from the transcriptional regulator E2F and activates E2F function.
R-HSA-69562 (Reactome) During G1, the activity of cyclin-dependent kinases (CDKs) is controlled by the CDK inhibitors (CKIs) CDKN1A (p21) and CDKN1B (p27), thereby preventing premature entry into S phase (see Guardavaccaro and Pagano, 2006). The efficient recognition and ubiquitination of p27 by the SCF (Skp2) complex requires the formation of a trimeric complex containing p27 and cyclin E/A:Cdk2.
R-HSA-69690 (Reactome) At the beginning of this reaction, 1 molecule of 'ATP', and 1 molecule of 'Cyclin E1:Cdk2 complex' are present. At the end of this reaction, 1 molecule of 'Cyclin E1:phospho-Cdk2 complex', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleoplasm' and is mediated by the 'kinase activity' of 'Myt1 kinase'.

R-HSA-69691 (Reactome) At the beginning of this reaction, 1 molecule of 'Cyclin E2:Cdk2 complex', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'Cyclin E2:phospho-Cdk2 complex', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleoplasm' and is mediated by the 'kinase activity' of 'Myt1 kinase'.

R-HSA-8848414 (Reactome) Activated PTK6 (BRK) binds to CDKN1B (p27KIP1) that is in a complex with CDK4 and cyclin D1 (CCND1). Since PTK6 increases cyclin E1 (CCNE1) levels downstream of ERBB2 while decreasing CDKN1B levels, PTK6 probably also associates with CDKN1B bound to the complex of CCNE1 and CDK2 (Xiang et al. 2008).
R-HSA-8848436 (Reactome) PTK6 (BRK) phosphorylates CDKN1B (p27KIP1) bound to the complex of CDK4 and CCND1 (cyclin D1) on tyrosine residue Y88 and possibly other tyrosines (e.g. Y89) (Patel et al. 2015). Based on the finding that PTK6 promotes ERBB2-induced increase in cyclin E1 (CCNE1) levels and decrease in CDKN1B levels (Xiang et al. 2008), and supported by the analogy with other SRC family kinases that phosphorylate CDKN1B (Grimmler et al. 2007), PTK6 is likely to also phosphorylate CDKN1B bound to the complex of CCNE1 and CDK2. Phosphorylation of CDKN1B (p27KIP1) on tyrosine residue Y88 by SRC family kinases dislodges the 3-10 helix of CDKN1B from the active site of CDK2 or CDK4, thus converting CDKN1B from a bound inhibitor to a bound non-inhibitor (Grimmler et al. 2007, Ray et al. 2009).
RB1:RNA primer-DNA

primer:origin duplex with DNA

damage		ArrowR-HSA-113503 (Reactome)
RB1:RNA primer-DNA

primer:origin duplex with DNA

damage		R-HSA-113643 (Reactome)
RB1:TFDP1:E2F1-3R-HSA-69227 (Reactome)
RB1R-HSA-188386 (Reactome)
RBL1:Cyclin E/A:CDK2ArrowR-HSA-1363314 (Reactome)
RBL1:E2F4:DP1/2:Cyclin E/A:CDK2ArrowR-HSA-1363311 (Reactome)
RBL1:E2F4:TFDP1,TFDP2R-HSA-1226095 (Reactome)
RBL1:E2F4:TFDP1,TFDP2R-HSA-1227671 (Reactome)
RBL1:E2F4:TFDP1,TFDP2R-HSA-1363311 (Reactome)
RBL1ArrowR-HSA-1362277 (Reactome)
RBL1ArrowR-HSA-1363274 (Reactome)
RBL1R-HSA-1363314 (Reactome)
RBL2:Cyclin E/A:CDK2ArrowR-HSA-1363306 (Reactome)
RBL2:E2F4,E2F5:TFDP1,TFDP2R-HSA-1226094 (Reactome)
RBL2:E2F4,E2F5:TFDP1,TFDP2R-HSA-1227670 (Reactome)
RBL2:E2F4,E2F5:TFDP1,TFDP2R-HSA-1362261 (Reactome)
RBL2:E2F4,E2F5:TFDP1,TFDP2R-HSA-1363303 (Reactome)
RBL2:E2F4/5:DP1/2:Cyclin E/A:CDK2ArrowR-HSA-1363303 (Reactome)
RBL2ArrowR-HSA-1363276 (Reactome)
RBL2R-HSA-1363306 (Reactome)
RNA primer-DNA

primer:origin duplex with DNA

damage		ArrowR-HSA-113504 (Reactome)
RNA primer-DNA

primer:origin duplex with DNA

damage		R-HSA-113503 (Reactome)
RNA primer-DNA

primer:origin

duplex		R-HSA-113504 (Reactome)
RPA1-4R-HSA-68916 (Reactome)
TFDP1:E2F1-3ArrowR-HSA-69227 (Reactome)
TOP2AArrowR-HSA-1362277 (Reactome)
Ub-p-T401,S672,1035-RBL2ArrowR-HSA-1363331 (Reactome)
UbiquitinArrowR-HSA-187574 (Reactome)
UbiquitinR-HSA-1363331 (Reactome)
UbiquitinR-HSA-187575 (Reactome)
WEE1mim-catalysisR-HSA-69195 (Reactome)
origin of replicationR-HSA-68960 (Reactome)
p-MCM2-7ArrowR-HSA-68954 (Reactome)
p-MuvB complexArrowR-HSA-1362270 (Reactome)
p-MuvB complexR-HSA-1362261 (Reactome)
p-S795-RB1ArrowR-HSA-69227 (Reactome)
p-S795-RB1R-HSA-113503 (Reactome)
p-T369,S640,S964,S975-RBL1ArrowR-HSA-1226095 (Reactome)
p-T369,S640,S964,S975-RBL1R-HSA-1363274 (Reactome)
p-T401,S672,1035-RBL2:SCF(Skp2):Cks1ArrowR-HSA-1363328 (Reactome)
p-T401,S672,1035-RBL2:SCF(Skp2):Cks1R-HSA-1363331 (Reactome)
p-T401,S672,1035-RBL2:SCF(Skp2):Cks1mim-catalysisR-HSA-1363331 (Reactome)
p-T401,S672,S1035-RBL2ArrowR-HSA-1226094 (Reactome)
p-T401,S672,S1035-RBL2R-HSA-1363276 (Reactome)
p-T401,S672,S1035-RBL2R-HSA-1363328 (Reactome)
p-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ArrowR-HSA-8848414 (Reactome)
p-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))R-HSA-8848436 (Reactome)
p-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))mim-catalysisR-HSA-8848436 (Reactome)
p-Y342-PTK6ArrowR-HSA-8848436 (Reactome)
p-Y342-PTK6R-HSA-8848414 (Reactome)
p-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ArrowR-HSA-8848436 (Reactome)
pre-replicative complexR-HSA-68919 (Reactome)
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