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

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9, 583, 1530315230619, 12, 25, 413710, 299, 42, 585223, 5511, 16, 18, 19, 28...2123815336013175, 57274513524786, 35, 396, 3514, 4941442, 54, 595639523927, 44, 6440, 4424, 34, 43, 624117cytosolnucleoplasmMCM7 TFDP2 PSMD14 MCM2 E2F1 TFDP1 PSMD11 SKP1 PSMB6 CDC7 E2F4 SKP1 TFDP1 ATPPSMB5 ORC5 E2F5 CyclinE2:phospho-Cdk2complexTFDP1 p-S130-CDKN1A MCM5 ORC4 SKP2 Aborted replicationcomplexMCM2 E2F4:TFDP1,TFDP2CDK2 SKP1 p-S28-LIN52 ADPPSMD9 CUL1 MCM4 CDC6MCM4 RB1PSMA2 RPA2 MCM5 SKP1 UBC(153-228) MCM7 MCM7 MCM2 ORC4 RNA primer-DNAprimer:originduplexMCM10 TFDP1 PSMC4 RPS27A(1-76) MCM5 ATPRBBP4 UBC(229-304) LIN54 PSME3 CDK6 MCM8 ubiquitinUBC(153-228) E2F4 CDC6 PRIM2 ORC1 ORC:originE2F5 CCNE1 CDKN1A ORC5 MCM4 CUL1 MCM3 E2F4 RB1 CDC45 CDKN2C CDKN1B CDK4 E2F1 Cyclin B:Cdk1complexPSMA3 ADPPRIM1 TFDP2 MNAT1 UBC(609-684) RBL2 ORC3 PSMC1 ORC5 CyclinD:Cdk4/6:p21/p27PPP2R3B p-T401,S672,S1035-RBL2 CDK2 MCM8 UBA52(1-76) CDKN2B CDKN1B MCM4 MCM10E2F4 p-T369,S640,S964,S975-RBL1E2F3 PSMA1 CCNB1 PRIM1 MCM10 CCNE2 RBL1POLE2 CDKN1BUBB(77-152) MCM6 CDC6 RBL2:Cyclin E/A:CDK2PP2ACKS1B UBB(77-152) E2F5 UBC(533-608) origin ofreplicationPSMD7 RPA3 ADPATPORC2 DBF4 RBL2 H2OPOLE ORC6 PiCCNAp-CDK2 CDKN1AMcm10:pre-replicative complexCCNE1 MCM2 ORC3 PCNAUBC(229-304) RBL1:E2F4:TFDP1,TFDP2SKP2 p16-INK4a p-T160-CDK2 RBBP4 E2F4 p-T187-CDKN1B ATPCDK2 phosphorylatedMcm2-7 complexCDK2 UBB(1-76) RNA primer-DNAprimer:originduplex with DNAdamagep21/p27Myc/Max heterodimerPSMD12 ATPUBC(305-380) MCM3 LIN37 CDC7 UBB(153-228) RBL2 E2F5 MCM3 MCM5 HDAC1 CDK2 TFDP2 RBL1:Cyclin E/A:CDK2DNA polymeraseepsilonPSME1 E2F4 p-MuvB complexTFDP2 ORC2 DBF4 CCNE2 CCNE1 PSMD10 CDKN1A Rb-E2F1/2/3:DP-1complexORC2 CyclinE1:phospho-Cdk2complexORC5 ORC6 ATPORC1 PSMA7 MAX MCM10 CCNE2 ORC2 CKS1B MCM8 RBL2ADPMcm10:activepre-replicativecomplexLIN52 CDKN2D ORC3 PKMYT1TFDP2 p-S130-CDKN1A MCM6 MCM2 RPA4 H2ORBL1 ATPCUL1 WEE1PSMD2 PSMC3 MCM3 CDK2 RPA1 PRIM2 MYC Cyclin E:Cdk2complexesp-T401,S672,S1035-RBL2E2F1TFDP2 CyclinE:phospho-Cdk2 (Thr160):phospho-RbORC5 ORC2 Cyclin E:Phosho-Cdk2(Thr 160)MCM5 ORC4 CDK2 TFDP2 ORC2 RBL1 ADPCUL1 RBL1:E2F4:TFDP1,TFDP2UBC(381-456) CDK2 RB1 CDK7 p21/p27CCNE1 LIN54 CyclinE/A:Cdk2:p27/p21complexCCNE1 SKP2 CCNE1 PSMB7 SKP2 CDT1p-CDK2 CDKN1BRBL2:E2F4/5:DP1/2:Cyclin E/A:CDK2LIN54 UBC(77-152) POLA1 MCM2 PSMD1 ORC2 PSMC5 LIN9 TFDP1 CDK2 MCM6 CDK1RBL1 LIN37 CDKN1B Cyclin E1:Cdk2complexCAKTFDP1 CDK2 ORC1 ORC3 POLE DBF4 DP-1:E2F1/2/3UBC(457-532) CDK2 ADPCDKN1A TOP2ACyclin EADPTFDP1 PRIM2 ADPSKP1 UBC(533-608) UBA52(1-76) Ub-p-T401,S672,1035-RBL2DDKCDC6 p-RB1 RBL2:E2F4/5:DP1/2CyclinE/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1 complexORC1 TFDP1 RBL1:E2F4:DP1/2:Cyclin E/A:CDK2ORC2 ATPORC6 RBL2 p-S795-RB1RB1 pre-replicativecomplexPSMC6 PSMB10 HDAC1:RBL2:E2F4/5:DP1/2PSMD4 MCM4 ORC5 POLA2 E2F4/5:DP1/2MCM8 RPA:Cdc45:CDK:DDK:Mcm10:pre-replicative complexCdc45:CDK:DDK:Mcm10:pre-replicative complexCKS1B RBL1 ORC6 Rb1:RNA primer-DNAprimer:originduplex with DNAdamageCCNE1 Cyclin DCyclinE/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1 complexMCM4 CCNE2 POLE2 ORC6 MCM6 MCM10 CyclinE:Cdk2:p21/p27complexMCM2 CDT1 MCM7 CDK1 Mcm2-7 complexMCM6 RPA1 PSMB3 RPA4 PSMB1 CyclinE:Phospho-Cdk2(Thr160):Rb complexCDC25AUBB(1-76) ORC3 p-T401,S672,1035-RBL2:SCF(Skp2):Cks1E2F5 CDK2 ORC4 ORC6 ubiquitinRBL2DNA polymerasealpha:primase:DNApolymerasealpha:origincomplexCDK2 TFDP1 SKP1 CDKN1B p-T187-CDKN1B PSMD5 RBL2 PiCKS1B E2F2 CDKN1A TFDP2 PSMF1 CUL1 POLE2 UBC(609-684) TFDP1 POLA2 RPS27A(1-76) RBL1CDK2 CDK2 UBC(305-380) HDAC1ATPE2F2 RBBP4 CDC7 MCM7 ORC3 Cyclin E/A:Cdk2ATPp-S130-CDKN1A MCM2 ATPp-T160-CDK2 ORC5 PP2ACDC6 CDC45DNA polymeraseepsilon:origincomplexATPTFDP2 MCM8 HDAC1:RBL1:E2F4:TFDP1,TFDP2CKS1BPOLE ATPCDT1 UBC(77-152) E2F1 E2F1:TFDP1E2F4 MCM6 RPA2 MCM7 MCM3 PSMC2 LIN37 PSME2 ORC1 ORC5 LIN9 PSMA5 SKP2 E2F3 RB1 E2F4 ADPCyclin E:Cdk2complexPiPSMB8 CDK2 POLA1 CyclinD:phospho-CDK4/6:p21/p27PSMA6 ORC4 ORC1 CUL1 MCM3 ORC4 UBC(1-76) Pi PSMD3 MCM5 UBC(457-532) p-CDK2 DNA polymerasealpha:primaseMCM8 MCM4 CDKN1B p-T401,S672,S1035-RBL2 ORC4 CDC6 SCF(Skp2) complexTFDP2 PSMD13 TFDP2 CDKMCM4 RBL1 UBB(153-228) DNA ReplicationFactor ACDC7 MCM8 E2F1 targetsRPA3 POLA1 MCM7 MCM5 ORC6 p-T160-CDK2 ORC:origin:cyclinB:cdk1 complexORC4 CDKN1A CyclinE/A:Cdk2:phospho-p27/p21MCM3 PSMB9 CDKN1AADPH2OADPCCNE2 SKP2 TFDP1 CCNH PRIM1 HDAC1 ORC3 26S proteasomeDBF4 CCNE2 UBC(1-76) CDK:DDK:Mcm10:pre-replicative complexSCF(Skp2):Cks1complexMCM3 ORC3 E2F1 CDK2 UBC(381-456) p-T187-CDKN1B PSMB4 RBL2:E2F4/5:DP1/2DREAM complexRBL1ORC1 MYBL2p-S28-LIN52 Cdk4/6:INK4A complexPSMD6 SCF(Skp2):Cks1complexE2F4 MCM8 ORC1 INK4AE2F4 PSMA4 E2F5 CDC25ACDC45 CKS1B MCM10 CDK2 TFDP1 ADPMuvB complexCyclin E2:Cdk2complexTFDP1 ADPTFDP1 PSMB2 Cdk4/6PSMD8 CyclinD:CDK4/6:p21/p27complexCDK1 E2F1POLA2 Cdk4/6CyclinE:phospho-Cdk2ComplexCDC6 MCM6 MCM7 CCNB1 ORC6 MCM5 DYRK1AE2F4 CCNE2 CDK2LIN9 MCM6 RBL2 TFDP1 12010, 295026, 385222


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  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)
CCNAProteinR-HSA-75202 (Reactome)
CCNB1 ProteinP14635 (Uniprot-TrEMBL)
CCNE1 ProteinP24864 (Uniprot-TrEMBL)
CCNE2 ProteinO96020 (Uniprot-TrEMBL)
CCNH ProteinP51946 (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)
CDK6 ProteinQ00534 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
CDK:DDK:Mcm10:pre-replicative complexComplexR-HSA-68561 (Reactome)
CDKN1A ProteinP38936 (Uniprot-TrEMBL)
CDKN1AProteinP38936 (Uniprot-TrEMBL)
CDKN1B ProteinP46527 (Uniprot-TrEMBL)
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)
Cdc45:CDK:DDK:Mcm10:pre-replicative complexComplexR-HSA-68564 (Reactome)
Cdk4/6:INK4A complexComplexR-HSA-182579 (Reactome)
Cdk4/6ProteinR-HSA-182699 (Reactome)
Cdk4/6R-HSA-69209 (Reactome)
Cyclin

D:CDK4/6:p21/p27

complex
ComplexR-HSA-69210 (Reactome)
Cyclin D:Cdk4/6:p21/p27ComplexR-HSA-141298 (Reactome)
Cyclin D:phospho-CDK4/6:p21/p27ComplexR-HSA-69212 (Reactome)
Cyclin E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1 complexComplexR-HSA-187568 (Reactome)
Cyclin

E/A:Cdk2:p27/p21

complex
ComplexR-HSA-187516 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1 complexComplexR-HSA-187565 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21ComplexR-HSA-187522 (Reactome)
Cyclin

E1:phospho-Cdk2

complex
ComplexR-HSA-68371 (Reactome)
Cyclin

E2:phospho-Cdk2

complex
ComplexR-HSA-68372 (Reactome)
Cyclin

E:Cdk2:p21/p27

complex
ComplexR-HSA-68376 (Reactome)
Cyclin E:Phospho-Cdk2(Thr160):Rb complexComplexR-HSA-188373 (Reactome)
Cyclin

E:phospho-Cdk2

Complex
ComplexR-HSA-68377 (Reactome)
Cyclin

E:phospho-Cdk2 (Thr

160):phospho-Rb
ComplexR-HSA-188391 (Reactome)
Cyclin B:Cdk1 complexComplexR-HSA-75032 (Reactome)
Cyclin DProteinR-HSA-182700 (Reactome)
Cyclin E/A:Cdk2ComplexR-HSA-187496 (Reactome)
Cyclin E1:Cdk2 complexComplexR-HSA-68378 (Reactome)
Cyclin E2:Cdk2 complexComplexR-HSA-68368 (Reactome)
Cyclin E:Cdk2 complexComplexR-HSA-157594 (Reactome)
Cyclin E:Cdk2 complexesComplexR-HSA-68374 (Reactome)
Cyclin E:Phosho-Cdk2 (Thr 160)ComplexR-HSA-188362 (Reactome)
Cyclin EProteinR-HSA-157462 (Reactome)
DBF4 ProteinQ9UBU7 (Uniprot-TrEMBL)
DDKComplexR-HSA-68388 (Reactome)
DNA Replication Factor AComplexR-HSA-68567 (Reactome)
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)
DP-1:E2F1/2/3ComplexR-HSA-1227905 (Reactome)
DREAM complexComplexR-HSA-1362264 (Reactome)
DYRK1AProteinQ13627 (Uniprot-TrEMBL)
E2F1 ProteinQ01094 (Uniprot-TrEMBL)
E2F1 targetsProteinR-HSA-539110 (Reactome)
E2F1:TFDP1ComplexR-HSA-68653 (Reactome)
E2F1ProteinQ01094 (Uniprot-TrEMBL)
E2F2 ProteinQ14209 (Uniprot-TrEMBL)
E2F3 ProteinO00716 (Uniprot-TrEMBL)
E2F4 ProteinQ16254 (Uniprot-TrEMBL)
E2F4/5:DP1/2ComplexR-HSA-1226072 (Reactome)
E2F4:TFDP1,TFDP2ComplexR-HSA-1362228 (Reactome)
E2F5 ProteinQ15329 (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)
INK4AR-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)
MCM10ProteinQ7L590 (Uniprot-TrEMBL)
MCM2 ProteinP49736 (Uniprot-TrEMBL)
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)
Mcm10:active

pre-replicative

complex
ComplexR-HSA-156564 (Reactome)
Mcm10:pre-replicative complexComplexR-HSA-68560 (Reactome)
Mcm2-7 complexComplexR-HSA-68558 (Reactome)
MuvB complexComplexR-HSA-1362248 (Reactome)
Myc/Max heterodimerComplexR-HSA-188378 (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:cyclin B:cdk1 complexComplexR-HSA-113637 (Reactome)
ORC:originComplexR-HSA-68540 (Reactome)
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)
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)
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:E2F4/5:DP1/2:Cyclin E/A:CDK2ComplexR-HSA-1363300 (Reactome)
RBL2:E2F4/5:DP1/2ComplexR-HSA-1226089 (Reactome)
RBL2ProteinQ08999 (Uniprot-TrEMBL)
RNA primer-DNA

primer:origin duplex with DNA

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

primer:origin

duplex
ComplexR-HSA-68425 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPA4 ProteinQ13156 (Uniprot-TrEMBL)
RPA:Cdc45:CDK:DDK:Mcm10:pre-replicative complexComplexR-HSA-68568 (Reactome)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
Rb-E2F1/2/3:DP-1 complexComplexR-HSA-68644 (Reactome)
Rb1:RNA primer-DNA

primer:origin duplex with DNA

damage
ComplexR-HSA-113646 (Reactome)
SCF(Skp2) complexComplexR-HSA-187541 (Reactome)
SCF(Skp2):Cks1 complexComplexR-HSA-187547 (Reactome)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SKP2 ProteinQ13309 (Uniprot-TrEMBL)
TFDP1 ProteinQ14186 (Uniprot-TrEMBL)
TFDP2 ProteinQ14188 (Uniprot-TrEMBL)
TOP2AProteinP11388 (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)
WEE1ProteinP30291 (Uniprot-TrEMBL)
origin of replicationR-NUL-68419 (Reactome)
p-CDK2 ProteinP24941 (Uniprot-TrEMBL)
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-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)
p16-INK4a ProteinP42771 (Uniprot-TrEMBL)
p21/p27ProteinR-HSA-182504 (Reactome)
p21/p27ProteinR-HSA-182558 (Reactome)
phosphorylated Mcm2-7 complexComplexR-HSA-68569 (Reactome)
pre-replicative complexComplexR-HSA-68559 (Reactome)
ubiquitinProteinR-HSA-68524 (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)
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)
Aborted replication complexArrowR-HSA-113643 (Reactome)
CAKmim-catalysisR-HSA-188350 (Reactome)
CAKmim-catalysisR-HSA-69223 (Reactome)
CCNAArrowR-HSA-1362300 (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)
CDK:DDK:Mcm10:pre-replicative complexArrowR-HSA-68918 (Reactome)
CDK:DDK:Mcm10:pre-replicative complexR-HSA-68917 (Reactome)
CDKN1AArrowR-HSA-187828 (Reactome)
CDKN1AR-HSA-187828 (Reactome)
CDKN1BArrowR-HSA-187506 (Reactome)
CDKN1BR-HSA-187506 (Reactome)
CDKR-HSA-68918 (Reactome)
CDT1ArrowR-HSA-68940 (Reactome)
CKS1BR-HSA-187545 (Reactome)
Cdc45:CDK:DDK:Mcm10:pre-replicative complexArrowR-HSA-68917 (Reactome)
Cdc45:CDK:DDK:Mcm10:pre-replicative complexR-HSA-68916 (Reactome)
Cdk4/6:INK4A complexArrowR-HSA-182594 (Reactome)
Cdk4/6:INK4A complexTBarR-HSA-69213 (Reactome)
Cdk4/6R-HSA-182594 (Reactome)
Cdk4/6R-HSA-69213 (Reactome)
Cyclin

D:CDK4/6:p21/p27

complex
ArrowR-HSA-69213 (Reactome)
Cyclin

D:CDK4/6:p21/p27

complex
R-HSA-141299 (Reactome)
Cyclin D:Cdk4/6:p21/p27ArrowR-HSA-141299 (Reactome)
Cyclin D:Cdk4/6:p21/p27R-HSA-69223 (Reactome)
Cyclin D:phospho-CDK4/6:p21/p27ArrowR-HSA-69223 (Reactome)
Cyclin D:phospho-CDK4/6:p21/p27mim-catalysisR-HSA-1226094 (Reactome)
Cyclin D:phospho-CDK4/6:p21/p27mim-catalysisR-HSA-1226095 (Reactome)
Cyclin D:phospho-CDK4/6:p21/p27mim-catalysisR-HSA-69227 (Reactome)
Cyclin E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1 complexArrowR-HSA-187575 (Reactome)
Cyclin E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1 complexR-HSA-187574 (Reactome)
Cyclin E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1 complexmim-catalysisR-HSA-187575 (Reactome)
Cyclin

E/A:Cdk2:p27/p21

complex
R-HSA-187520 (Reactome)
Cyclin

E/A:Cdk2:p27/p21

complex
mim-catalysisR-HSA-187520 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1 complexArrowR-HSA-187552 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1 complexR-HSA-187575 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21ArrowR-HSA-187520 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21R-HSA-187552 (Reactome)
Cyclin

E1:phospho-Cdk2

complex
ArrowR-HSA-69690 (Reactome)
Cyclin

E2:phospho-Cdk2

complex
ArrowR-HSA-69691 (Reactome)
Cyclin

E:Cdk2:p21/p27

complex
ArrowR-HSA-69562 (Reactome)
Cyclin E:Phospho-Cdk2(Thr160):Rb complexArrowR-HSA-188386 (Reactome)
Cyclin E:Phospho-Cdk2(Thr160):Rb complexR-HSA-188390 (Reactome)
Cyclin E:Phospho-Cdk2(Thr160):Rb complexmim-catalysisR-HSA-188390 (Reactome)
Cyclin

E:phospho-Cdk2

Complex
ArrowR-HSA-69195 (Reactome)
Cyclin

E:phospho-Cdk2

Complex
R-HSA-69199 (Reactome)
Cyclin

E:phospho-Cdk2 (Thr

160):phospho-Rb
ArrowR-HSA-188390 (Reactome)
Cyclin B:Cdk1 complexArrowR-HSA-113505 (Reactome)
Cyclin B:Cdk1 complexR-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 E1:Cdk2 complexR-HSA-69690 (Reactome)
Cyclin E2:Cdk2 complexR-HSA-69691 (Reactome)
Cyclin E:Cdk2 complexArrowR-HSA-69191 (Reactome)
Cyclin E:Cdk2 complexR-HSA-157906 (Reactome)
Cyclin E:Cdk2 complexesArrowR-HSA-157906 (Reactome)
Cyclin E:Cdk2 complexesArrowR-HSA-69199 (Reactome)
Cyclin E:Cdk2 complexesR-HSA-188350 (Reactome)
Cyclin E:Cdk2 complexesR-HSA-69195 (Reactome)
Cyclin E:Cdk2 complexesR-HSA-69562 (Reactome)
Cyclin E:Phosho-Cdk2 (Thr 160)ArrowR-HSA-188350 (Reactome)
Cyclin E:Phosho-Cdk2 (Thr 160)R-HSA-188386 (Reactome)
Cyclin ER-HSA-69191 (Reactome)
DDKR-HSA-68918 (Reactome)
DDKmim-catalysisR-HSA-68954 (Reactome)
DNA Replication Factor AR-HSA-68916 (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)
DP-1:E2F1/2/3ArrowR-HSA-69227 (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)
E2F4/5:DP1/2ArrowR-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)
MCM10R-HSA-68919 (Reactome)
MYBL2ArrowR-HSA-1362300 (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)
Mcm2-7 complexR-HSA-68954 (Reactome)
MuvB complexR-HSA-1362270 (Reactome)
Myc/Max heterodimerArrowR-HSA-188345 (Reactome)
ORC:origin:cyclin B:cdk1 complexArrowR-HSA-113638 (Reactome)
ORC:originR-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 kept in check by the CDK inhibitors (CKIs) p27 and p21, 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'.

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:E2F4/5:DP1/2:Cyclin E/A:CDK2ArrowR-HSA-1363303 (Reactome)
RBL2:E2F4/5:DP1/2R-HSA-1226094 (Reactome)
RBL2:E2F4/5:DP1/2R-HSA-1227670 (Reactome)
RBL2:E2F4/5:DP1/2R-HSA-1362261 (Reactome)
RBL2:E2F4/5:DP1/2R-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)
RPA:Cdc45:CDK:DDK:Mcm10:pre-replicative complexArrowR-HSA-68914 (Reactome)
RPA:Cdc45:CDK:DDK:Mcm10:pre-replicative complexArrowR-HSA-68916 (Reactome)
RPA:Cdc45:CDK:DDK:Mcm10:pre-replicative complexArrowR-HSA-68960 (Reactome)
Rb-E2F1/2/3:DP-1 complexR-HSA-69227 (Reactome)
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)
SCF(Skp2) complexR-HSA-187545 (Reactome)
SCF(Skp2):Cks1 complexArrowR-HSA-1363331 (Reactome)
SCF(Skp2):Cks1 complexArrowR-HSA-187545 (Reactome)
SCF(Skp2):Cks1 complexArrowR-HSA-187574 (Reactome)
SCF(Skp2):Cks1 complexR-HSA-1363328 (Reactome)
SCF(Skp2):Cks1 complexR-HSA-187552 (Reactome)
TOP2AArrowR-HSA-1362277 (Reactome)
Ub-p-T401,S672,1035-RBL2ArrowR-HSA-1363331 (Reactome)
WEE1mim-catalysisR-HSA-69195 (Reactome)
origin of replicationR-HSA-68960 (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)
p21/p27R-HSA-69213 (Reactome)
p21/p27R-HSA-69562 (Reactome)
p21/p27mim-catalysisR-HSA-69562 (Reactome)
phosphorylated Mcm2-7 complexArrowR-HSA-68954 (Reactome)
pre-replicative complexR-HSA-68919 (Reactome)
ubiquitinArrowR-HSA-187574 (Reactome)
ubiquitinR-HSA-1363331 (Reactome)
ubiquitinR-HSA-187575 (Reactome)
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