S Phase (Homo sapiens)

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561213339, 38314, 7, 23-25, 309, 10, 17, 291, 3934, 4086183, 7, 24, 25, 41209, 3310, 14, 28, 339-1110, 11352, 19, 32, 3711833322, 363, 21cytosolnucleoplasmAc-Cohesin:PDS5:WAPAL:Centromerep-T160-CDK2 UBC(533-608) PSMF1 CDC25B UBA52(1-76) UBC(1-76) Mitotic PrometaphaseCUL1 WAPAL CCNA1 CDK2 CDK7 CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BCCNE1 ESCO2 PSMB2 UBC(153-228) PSMB7 PSMB7 PDS5B PSMD7 p-T160-CDK2 PSMA6 UBC(609-684) CDKN1B PSMB11 CCNE2 PSMB6 CCNA2 UBB(153-228) PSMA1 PSMA7 UBC(381-456) ATPUBA52(1-76) CCNH CDKN1B PSMD10 UBB(153-228) p-T286-CCND1 UBA52(1-76) CCNA2 CDK2 p-S130-CDKN1A CUL1 p-T286-CCND1 RPS27A(1-76) PSMB8 PDS5A E2F5 SMC1A SKP2 p-T286-CCND1 STAG2 PSMD14 CoA-SHCCNA1 UBB(153-228) CCNA:CDK2STAG2 CABLES1PDS5B SKP2 CCNE1 PSMA5 PSMB6 CKS1B PSMA1 WEE1Sister Centromere p-T145-CDKN1A CDK4 CCNA2 WAPAL CDK2 p-T160-CDK2 RPS27A(1-76) UBC(229-304) CKS1B WAPAL CDCA5 PSMC5 LIN37 STAG1 CCND1:CDK4CCNA1 ESCO1 PSMD5 ATPPSMA4 CCND1 p-T286-CCND1CCND1 E2F4 PSMD12 CCNE1 UBC(305-380) SKP1 PSMA8 PSMB4 p-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))2xAcK-SMC3 SisterCentromeres:Ac-Cohesin:PDS5:CDCA5:WAPALp-S130-CDKN1A PSMD1 SKP2 CyclinA:Cdk2:p21/p27complexPSMD9 UBC(153-228) ADPRPS27A(1-76) UBB(1-76) PDS5B PSMD7 SMC1A PSMD11 TFDP2 PSMC5 PDS5A PSMB3 SKP1 CDK2STAG1 H2OCDKN1AWAPAL Sister Chromosomal Arm PSMA5 p-S28-LIN52 TFDP1 CDCA5 TFDP2 STAG2 CCNA1 CCNA1 STAG2 CCNE1 PSMD14 PSMD2 UBC(381-456) CAKCCNA2 p-Y342-PTK6MYC PSMD4 PSMC1 CDKN1AUBC(1-76) PSMD8 p-T309,S474-AKT2 PSMB5 TFDP1 UBC(533-608) ADPp-T,p-S-AKTCCNE2 CDKN1BCCNA1 CDKN1A CCNE2 RAD21 UBB(77-152) CDKN1B ATPp-FZR1 UBC(1-76) PSMB2 PDS5B PSMC3 p-T305,S472-AKT3 PSME3 p-Y15-CDK2 PSMC6 CDC25A gene PSMD6 PDS5B UbMNAT1 CKS1BCCNA1 UBB(153-228) SMC3 UBA52(1-76) UBC(153-228) SMC3 UBB(1-76) UBC(305-380) PSMD13 UBC(609-684) CCND1 CUL1 SKP1 PSMD3 CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))CCNA2 CCNA2 UBC(229-304) UBC(77-152) PSME1 CDK4 RBBP4 SKP1 CDC25AUBC(305-380) CDC25A WAPAL PSMB9 p-T160-CDK2 UBC(77-152) PSMC3 PSME2 PSMD10 Ac-CoAp-T160-CDK2 PSMC4 UBB(77-152) RAD21 PSMA2 CDK4 PSME1 RBL2 CDKN1A,CDKN1BPSMA3 Sister ChromosomalArmAc-Cohesin:PDS5:WAPAL:Chromosomal ArmCDK2 PSMB1 Sister CentromereCCNA:CDK2Pip-S795-RB1 FZR1 p-S130-CDKN1A PSMD9 UBC(533-608) phospho(T286)-CyclinD1:Cdk4WAPAL RAD21 p-T157-CDKN1B CCNA2 Sister Chromosomal Arm CDK4 MitoticTelophase/CytokinesisUBB(77-152) SMC1A PSMC2 multi-ubiquitinatedphospho-(T286)Cyclin D1PSMA4 STAG1 SisterChromosomalArms:Ac-Cohesin:PDS5:CDCA5:WAPALMAX CDKN1A STAG2 UBC(457-532) ADPCCNE1 CDKN1A PSMD2 PSMA7 PSMB1 SMC1A PDS5A SHFM1 CUL1:SKP1:SKP2:CKS1BCyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinCCNA1 CDK2 ESCOFZR1,p-S795-RB1CDKN1B p-T308,S473-AKT1 Cdc25 A/BPSMC1 Cohesin:PDS5:WAPAL:Chromosomal ArmCDKN1A PSMD13 ADPPSMB10 2xAcK-SMC3 UBC(457-532) p-Y88-CDKN1B 26S proteasomeCCNA1 PSMA3 p-T-CDKN1A/BPSMD12 p-T187-CDKN1B ADPCDK4 p-T187-CDKN1B RAD21 CKS1B PSMB4 p-T187-CDKN1B DREAM complex:CDC25AgenePSMC2 PSMD4 PSMB3 UBC(609-684) PSMD3 UBC(1-76) CDK4 Synthesis of DNACCNE1 CCNA:p-T160-CDK2STAG1 p-T187-CDKN1B CyclinE/A:p-T160-CDK2:CDKN1A,CDKN1BPSME4 UBB(77-152) CDKN1B p-FZR1,p-RB1PSMF1 LIN54 ATPSKP2 ATP2xAcK-SMC3 CCNAPSME2 CCNE2 UBC(457-532) CDCA5p-T160-CDK2 Sister Centromere ATPUBB(1-76) PSMB8 PDS5A CCNA:p-Y15-CDK2PSMD1 E2F1:TFDP1,TFDP2:CDC25A genePSMC6 CyclinE/A:p-T160-CDK2:p-S130-CDKN1A,p-T187-CDKN1BPDS5A LIN9 CyclinA:Cdk2:phospho-p27/p21 complexPSMD6 PDS5A CCNA1 CDKN1B UBC(229-304) p-Y342-PTK6 2xAcK-SMC3 CDC25A gene 26S proteasomeATPE2F1 UBC(609-684) MYC:MAX:CDC25A geneCCNA1 PSMD11 p-T286-CCND1PSME3 PSMB10 STAG1 RAD21 ADPCCNA1 ADPCCNA2 Cohesin:PDS5:WAPAL:CentromereCCNE2 CCNA2 UBC(153-228) UBB(1-76) PSMA6 CUL1:SKP1:SKP2STAG1 CCNA2 SHFM1 UBC(457-532) phospho(T286)-CyclinD1:Cdk4CDKN1BUbhyperphosphorylated RB1 UBC(381-456) UBC(77-152) GSK3BCCNA2 RAD21 UBC(533-608) UBC(229-304) SMC1A PSMD8 STAG2 PSMB5 p-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))PSMD5 PSMA2 CDC25A gene RPS27A(1-76) CCND1 UBC(305-380) CDKN1A,CDKN1BPDS5B Sister Chromosomal Arm CCNA:p-T160-CDK2,CCNE:p-T160-CDK2PSMC4 ADPSMC1A UBC(77-152) PSMB9 CCNE1 Sister Centromere ATPp-S130-CDKN1A CUL1 Ubiquitin ligaseUBC(381-456) CCNE1 CDK2 CDC25A geneCDK2 CCNA2 15, 261272615, 2619, 3726322161


DNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues, the E type cyclins shared by the G1 and S phases, are destroyed and the levels of the mitotic cyclins rise. View original pathway at Reactome.


Pathway is converted from Reactome ID: 69242
Reactome version: 74

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  1. Patel P, Asbach B, Shteyn E, Gomez C, Coltoff A, Bhuyan S, Tyner AL, Wagner R, Blain SW.; ''Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.''; PubMed Europe PMC Scholia
  2. Galaktionov K, Chen X, Beach D.; ''Cdc25 cell-cycle phosphatase as a target of c-myc.''; PubMed Europe PMC Scholia
  3. Nishiyama T, Ladurner R, Schmitz J, Kreidl E, Kreidl E, Schleiffer A, Bhaskara V, Bando M, Shirahige K, Hyman AA, Mechtler K, Peters JM.; ''Sororin mediates sister chromatid cohesion by antagonizing Wapl.''; PubMed Europe PMC Scholia
  4. Gordillo M, Vega H, Trainer AH, Hou F, Sakai N, Luque R, Kayserili H, Basaran S, Skovby F, Hennekam RC, Uzielli ML, Schnur RE, Manouvrier S, Chang S, Blair E, Hurst JA, Forzano F, Meins M, Simola KO, Raas-Rothschild A, Schultz RA, McDaniel LD, Ozono K, Inui K, Zou H, Jabs EW.; ''The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity.''; PubMed Europe PMC Scholia
  5. Guo Y, Yang K, Harwalkar J, Nye JM, Mason DR, Garrett MD, Hitomi M, Stacey DW.; ''Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal degradation and allows efficient DNA synthesis.''; PubMed Europe PMC Scholia
  6. Diehl JA, Sherr CJ.; ''A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase.''; PubMed Europe PMC Scholia
  7. Hou F, Zou H.; ''Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion.''; PubMed Europe PMC Scholia
  8. 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
  9. 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
  10. Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H.; ''p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.''; PubMed Europe PMC Scholia
  11. Carrano AC, Eytan E, Hershko A, Pagano M.; ''SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.''; PubMed Europe PMC Scholia
  12. Diehl JA, Zindy F, Sherr CJ.; ''Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway.''; PubMed Europe PMC Scholia
  13. Blomberg I, Hoffmann I.; ''Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases.''; PubMed Europe PMC Scholia
  14. Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP.; ''Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.''; PubMed Europe PMC Scholia
  15. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  16. Bembenek J, Yu H.; ''Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a.''; PubMed Europe PMC Scholia
  17. Bornstein G, Bloom J, Sitry-Shevah D, Nakayama K, Pagano M, Hershko A.; ''Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase.''; PubMed Europe PMC Scholia
  18. Orend G, Hunter T, Ruoslahti E.; ''Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells.''; PubMed Europe PMC Scholia
  19. 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
  20. Benzeno S, Lu F, Guo M, Barbash O, Zhang F, Herman JG, Klein PS, Rustgi A, Diehl JA.; ''Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.''; PubMed Europe PMC Scholia
  21. Rankin S, Ayad NG, Kirschner MW.; ''Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates.''; PubMed Europe PMC Scholia
  22. Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A, Santoro M.; ''Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.''; PubMed Europe PMC Scholia
  23. Vega H, Waisfisz Q, Gordillo M, Sakai N, Yanagihara I, Yamada M, van Gosliga D, Kayserili H, Xu C, Ozono K, Jabs EW, Inui K, Joenje H.; ''Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion.''; PubMed Europe PMC Scholia
  24. Whelan G, Kreidl E, Kreidl E, Wutz G, Egner A, Peters JM, Eichele G.; ''Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin.''; PubMed Europe PMC Scholia
  25. Zhang J, Shi X, Li Y, Kim BJ, Jia J, Huang Z, Yang T, Fu X, Jung SY, Wang Y, Zhang P, Kim ST, Pan X, Qin J.; ''Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast.''; PubMed Europe PMC Scholia
  26. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
  27. Sarshad AA, Corcoran M, Al-Muzzaini B, Borgonovo-Brandter L, Von Euler A, Lamont D, Visa N, Percipalle P.; ''Glycogen synthase kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells.''; PubMed Europe PMC Scholia
  28. Zhu XH, Nguyen H, Halicka HD, Traganos F, Koff A.; ''Noncatalytic requirement for cyclin A-cdk2 in p27 turnover.''; PubMed Europe PMC Scholia
  29. Mitra J, Enders GH, Azizkhan-Clifford J, Lengel KL.; ''Dual regulation of the anaphase promoting complex in human cells by cyclin A-Cdk2 and cyclin A-Cdk1 complexes.''; PubMed Europe PMC Scholia
  30. Van Den Berg DJ, Francke U.; ''Roberts syndrome: a review of 100 cases and a new rating system for severity.''; PubMed Europe PMC Scholia
  31. Jackman M, Kubota Y, den Elzen N, Hagting A, Pines J.; ''Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm.''; PubMed Europe PMC Scholia
  32. Litovchick L, Sadasivam S, Florens L, Zhu X, Swanson SK, Velmurugan S, Chen R, Washburn MP, Liu XS, DeCaprio JA.; ''Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.''; PubMed Europe PMC Scholia
  33. 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
  34. Wu CL, Kirley SD, Xiao H, Chuang Y, Chung DC, Zukerberg LR.; ''Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.''; PubMed Europe PMC Scholia
  35. Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G.; ''Cyclin A is required at two points in the human cell cycle.''; PubMed Europe PMC Scholia
  36. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC.; ''Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells.''; PubMed Europe PMC Scholia
  37. 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
  38. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ.; ''The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.''; PubMed Europe PMC Scholia
  39. Xiang B, Chatti K, Qiu H, Lakshmi B, Krasnitz A, Hicks J, Yu M, Miller WT, Muthuswamy SK.; ''Brk is coamplified with ErbB2 to promote proliferation in breast cancer.''; PubMed Europe PMC Scholia
  40. Gu Y, Rosenblatt J, Morgan DO.; ''Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.''; PubMed Europe PMC Scholia
  41. Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole KE, De Baere E, Decroos C, Di Donato N, Ernst S, Francey LJ, Gyftodimou Y, Hirashima K, Hullings M, Ishikawa Y, Jaulin C, Kaur M, Kiyono T, Lombardi PM, Magnaghi-Jaulin L, Mortier GR, Nozaki N, Petersen MB, Seimiya H, Siu VM, Suzuki Y, Takagaki K, Wilde JJ, Willems PJ, Prigent C, Gillessen-Kaesbach G, Christianson DW, Kaiser FJ, Jackson LG, Hirota T, Krantz ID, Shirahige K.; ''HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.''; PubMed Europe PMC Scholia


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113503view11:58, 2 November 2020ReactomeTeamReactome version 74
112703view16:10, 9 October 2020ReactomeTeamReactome version 73
101618view11:48, 1 November 2018ReactomeTeamreactome version 66
101154view21:34, 31 October 2018ReactomeTeamreactome version 65
100681view20:07, 31 October 2018ReactomeTeamreactome version 64
100231view16:52, 31 October 2018ReactomeTeamreactome version 63
99783view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99337view12:47, 31 October 2018ReactomeTeamreactome version 62
93537view11:26, 9 August 2017ReactomeTeamreactome version 61
86636view09:22, 11 July 2016ReactomeTeamreactome version 56
83395view11:07, 18 November 2015ReactomeTeamVersion54
81589view13:07, 21 August 2015ReactomeTeamVersion53
77049view08:35, 17 July 2014ReactomeTeamFixed remaining interactions
76754view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76079view10:14, 11 June 2014ReactomeTeamRe-fixing comment source
75789view11:32, 10 June 2014ReactomeTeamReactome 48 Update
75139view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74786view08:52, 30 April 2014ReactomeTeamNew pathway

External references


View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-177750 (Reactome)
26S proteasomeComplexR-HSA-68819 (Reactome)
2xAcK-SMC3 ProteinQ9UQE7 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
Ac-Cohesin:PDS5:WAPAL:CentromereComplexR-HSA-2473149 (Reactome)
Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmComplexR-HSA-2473153 (Reactome)
CABLES1ProteinQ8TDN4 (Uniprot-TrEMBL)
CAKComplexR-HSA-69221 (Reactome)
CCNA1 ProteinP78396 (Uniprot-TrEMBL)
CCNA2 ProteinP20248 (Uniprot-TrEMBL)
CCNA:CDK2ComplexR-HSA-141608 (Reactome)
CCNA:CDK2ComplexR-HSA-187501 (Reactome)
CCNA:p-T160-CDK2,CCNE:p-T160-CDK2ComplexR-HSA-8848491 (Reactome)
CCNA:p-T160-CDK2ComplexR-HSA-187952 (Reactome)
CCNA:p-Y15-CDK2ComplexR-HSA-187907 (Reactome)
CCNAComplexR-HSA-170089 (Reactome)
CCND1 ProteinP24385 (Uniprot-TrEMBL)
CCND1:CDK4ComplexR-HSA-113844 (Reactome)
CCNE1 ProteinP24864 (Uniprot-TrEMBL)
CCNE2 ProteinO96020 (Uniprot-TrEMBL)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CDC25A ProteinP30304 (Uniprot-TrEMBL)
CDC25A gene ProteinENSG00000164045 (Ensembl)
CDC25A geneGeneProductENSG00000164045 (Ensembl)
CDC25AProteinP30304 (Uniprot-TrEMBL)
CDC25B ProteinP30305 (Uniprot-TrEMBL)
CDCA5 ProteinQ96FF9 (Uniprot-TrEMBL)
CDCA5ProteinQ96FF9 (Uniprot-TrEMBL)
CDK2 ProteinP24941 (Uniprot-TrEMBL)
CDK2ProteinP24941 (Uniprot-TrEMBL)
CDK4 ProteinP11802 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
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)
CKS1B ProteinP61024 (Uniprot-TrEMBL)
CKS1BProteinP61024 (Uniprot-TrEMBL)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
CUL1:SKP1:SKP2:CKS1BComplexR-HSA-187547 (Reactome)
CUL1:SKP1:SKP2ComplexR-HSA-187541 (Reactome)
Cdc25 A/BComplexR-HSA-187904 (Reactome)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
Cohesin:PDS5:WAPAL:CentromereComplexR-HSA-2545177 (Reactome)
Cohesin:PDS5:WAPAL:Chromosomal ArmComplexR-HSA-2545179 (Reactome)


ComplexR-HSA-187926 (Reactome)
Cyclin A:Cdk2:phospho-p27/p21 complexComplexR-HSA-187912 (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:p-T160-CDK2:CDKN1A,CDKN1BComplexR-HSA-187516 (Reactome)
Cyclin E/A:p-T160-CDK2:p-S130-CDKN1A,p-T187-CDKN1BComplexR-HSA-187522 (Reactome)
DREAM complex:CDC25A geneComplexR-HSA-8964470 (Reactome)
E2F1 ProteinQ01094 (Uniprot-TrEMBL)
E2F1:TFDP1,TFDP2:CDC25A geneComplexR-HSA-8961960 (Reactome)
E2F4 ProteinQ16254 (Uniprot-TrEMBL)
E2F5 ProteinQ15329 (Uniprot-TrEMBL)
ESCO1 ProteinQ5FWF5 (Uniprot-TrEMBL)
ESCO2 ProteinQ56NI9 (Uniprot-TrEMBL)
ESCOComplexR-HSA-2468046 (Reactome)
FZR1 ProteinQ9UM11 (Uniprot-TrEMBL)
FZR1,p-S795-RB1ComplexR-HSA-187963 (Reactome)
GSK3BProteinP49841 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
LIN37 ProteinQ96GY3 (Uniprot-TrEMBL)
LIN54 ProteinQ6MZP7 (Uniprot-TrEMBL)
LIN9 ProteinQ5TKA1 (Uniprot-TrEMBL)
MAX ProteinP61244 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
MYC ProteinP01106 (Uniprot-TrEMBL)
MYC:MAX:CDC25A geneComplexR-HSA-8932399 (Reactome)
Mitotic Telophase/CytokinesisPathwayR-HSA-68884 (Reactome) In this final phase of mitosis, new membranes are formed around two sets of chromatids and two daughter cells are formed. The chromosomes and the spindle fibers disperse, and the fiber ring around the center of the cell, composed of actin, contracts, pinching the cell into two daughter cells.
Mitotic PrometaphasePathwayR-HSA-68877 (Reactome) The dissolution of the nuclear membrane marks the beginning of the prometaphase. Kinetochores are created when proteins attach to the centromeres. Microtubules then attach at the kinetochores, and the chromosomes begin to move to the metaphase plate.
PDS5A ProteinQ29RF7 (Uniprot-TrEMBL)
PDS5B ProteinQ9NTI5 (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)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (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)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:43474 (ChEBI)
RAD21 ProteinO60216 (Uniprot-TrEMBL)
RBBP4 ProteinQ09028 (Uniprot-TrEMBL)
RBL2 ProteinQ08999 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SKP2 ProteinQ13309 (Uniprot-TrEMBL)
SMC1A ProteinQ14683 (Uniprot-TrEMBL)
SMC3 ProteinQ9UQE7 (Uniprot-TrEMBL)
STAG1 ProteinQ8WVM7 (Uniprot-TrEMBL)
STAG2 ProteinQ8N3U4 (Uniprot-TrEMBL)
Sister Centromeres:Ac-Cohesin:PDS5:CDCA5:WAPALComplexR-HSA-1638799 (Reactome)


ComplexR-HSA-1638802 (Reactome)
Sister Centromere R-ALL-1638792 (Reactome)
Sister CentromereR-ALL-1638792 (Reactome)
Sister Chromosomal ArmR-ALL-1638790 (Reactome)
Sister Chromosomal Arm R-ALL-1638790 (Reactome)
Synthesis of DNAPathwayR-HSA-69239 (Reactome) The actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of the primer. The DNA replication preinitiation events begin in late M or early G1 phase.
TFDP1 ProteinQ14186 (Uniprot-TrEMBL)
TFDP2 ProteinQ14188 (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)
UbComplexR-HSA-113595 (Reactome)
UbComplexR-HSA-68524 (Reactome)
Ubiquitin ligaseR-HSA-69593 (Reactome)
WAPAL ProteinQ7Z5K2 (Uniprot-TrEMBL)
WEE1ProteinP30291 (Uniprot-TrEMBL)
hyperphosphorylated 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.


Cyclin D1
ComplexR-HSA-177997 (Reactome)
p-FZR1 ProteinQ9UM11 (Uniprot-TrEMBL)
p-FZR1,p-RB1ComplexR-HSA-187920 (Reactome)
p-S130-CDKN1A ProteinP38936 (Uniprot-TrEMBL)
p-S28-LIN52 ProteinQ52LA3 (Uniprot-TrEMBL)
p-S795-RB1 ProteinP06400 (Uniprot-TrEMBL)
p-T,p-S-AKTComplexR-HSA-202074 (Reactome)
p-T-CDKN1A/BComplexR-HSA-198605 (Reactome)
p-T145-CDKN1A ProteinP38936 (Uniprot-TrEMBL)
p-T157-CDKN1B ProteinP46527 (Uniprot-TrEMBL)
p-T160-CDK2 ProteinP24941 (Uniprot-TrEMBL)
p-T187-CDKN1B ProteinP46527 (Uniprot-TrEMBL)
p-T286-CCND1 ProteinP24385 (Uniprot-TrEMBL)
p-T286-CCND1ProteinP24385 (Uniprot-TrEMBL)
p-T305,S472-AKT3 ProteinQ9Y243 (Uniprot-TrEMBL)
p-T308,S473-AKT1 ProteinP31749 (Uniprot-TrEMBL)
p-T309,S474-AKT2 ProteinP31751 (Uniprot-TrEMBL)
p-Y15-CDK2 ProteinP24941 (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)
phospho(T286)-Cyclin D1:Cdk4ComplexR-HSA-75812 (Reactome)
phospho(T286)-Cyclin D1:Cdk4ComplexR-HSA-75814 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-187574 (Reactome)
26S proteasomemim-catalysisR-HSA-75825 (Reactome)
ADPArrowR-HSA-174164 (Reactome)
ADPArrowR-HSA-187520 (Reactome)
ADPArrowR-HSA-187916 (Reactome)
ADPArrowR-HSA-187948 (Reactome)
ADPArrowR-HSA-187949 (Reactome)
ADPArrowR-HSA-198613 (Reactome)
ADPArrowR-HSA-75820 (Reactome)
ADPArrowR-HSA-8848436 (Reactome)
ATPR-HSA-174164 (Reactome)
ATPR-HSA-187520 (Reactome)
ATPR-HSA-187916 (Reactome)
ATPR-HSA-187948 (Reactome)
ATPR-HSA-187949 (Reactome)
ATPR-HSA-198613 (Reactome)
ATPR-HSA-75820 (Reactome)
ATPR-HSA-8848436 (Reactome)
Ac-CoAR-HSA-2468039 (Reactome)
Ac-CoAR-HSA-2473152 (Reactome)
Ac-Cohesin:PDS5:WAPAL:CentromereArrowR-HSA-2473152 (Reactome)
Ac-Cohesin:PDS5:WAPAL:CentromereR-HSA-2473151 (Reactome)
Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmArrowR-HSA-2468039 (Reactome)
Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmR-HSA-2468041 (Reactome)
CABLES1ArrowR-HSA-174164 (Reactome)
CAKmim-catalysisR-HSA-187949 (Reactome)
CCNA:CDK2ArrowR-HSA-174054 (Reactome)
CCNA:CDK2ArrowR-HSA-174110 (Reactome)
CCNA:CDK2ArrowR-HSA-174273 (Reactome)
CCNA:CDK2R-HSA-174164 (Reactome)
CCNA:CDK2R-HSA-174273 (Reactome)
CCNA:CDK2R-HSA-187934 (Reactome)
CCNA:CDK2R-HSA-187949 (Reactome)
CCNA:p-T160-CDK2,CCNE:p-T160-CDK2ArrowR-HSA-187574 (Reactome)
CCNA:p-T160-CDK2ArrowR-HSA-187949 (Reactome)
CCNA:p-T160-CDK2mim-catalysisR-HSA-187948 (Reactome)
CCNA:p-Y15-CDK2ArrowR-HSA-174164 (Reactome)
CCNA:p-Y15-CDK2R-HSA-174110 (Reactome)
CCNAR-HSA-174054 (Reactome)
CCND1:CDK4R-HSA-75820 (Reactome)
CDC25A geneR-HSA-188345 (Reactome)
CDC25AArrowR-HSA-188345 (Reactome)
CDCA5R-HSA-2468041 (Reactome)
CDCA5R-HSA-2473151 (Reactome)
CDK2R-HSA-174054 (Reactome)
CDKN1A,CDKN1BR-HSA-187934 (Reactome)
CDKN1A,CDKN1BR-HSA-198613 (Reactome)
CDKN1A,CDKN1Bmim-catalysisR-HSA-187934 (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)
CKS1BR-HSA-187545 (Reactome)
CUL1:SKP1:SKP2:CKS1BArrowR-HSA-187545 (Reactome)
CUL1:SKP1:SKP2:CKS1BArrowR-HSA-187574 (Reactome)
CUL1:SKP1:SKP2:CKS1BR-HSA-187552 (Reactome)