S Phase (Homo sapiens)

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3813, 35111, 17, 20, 373, 3518, 23, 32, 352, 8-10, 22...30164019403931, 32363331, 32, 3513, 25, 26, 3228, 3641, 6131, 2, 8, 10, 211213165, 277nucleoplasmcytosolPSMD6 UBB(1-76) PSMA4 CDKN1A,CDKN1BADPPSMB6 PSMC2 RAD21 LIN9 CCNA1 STAG2 Sister Centromere CCNA2 LIN54 CDK4 CDKN1Ap-RB1 WAPAL CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinCCNE1 PSME3 PDS5A PSMB3 PDS5B PSMD4 CCNA1 p-T160-CDK2 RAD21 ATPCDKN1BUBA52(1-76) PSME2 multi-ubiquitinatedphospho-(T286)Cyclin D1CKS1B UBC(381-456) UBC(609-684) CUL1:SKP1:SKP2:CKS1BSKP1 WAPAL STAG2 SKP2 WAPAL UBC(609-684) UBC(229-304) CCNE1 CDC25APSMD9 PSMB10 CCNA:p-T160-CDK2p-T187-CDKN1B LIN37 CUL1 PSMD3 Sister Centromere CCNA2 Sister ChromosomalArmPSMB7 Cohesin:PDS5:WAPAL:CentromereCCNE2 2xAcK-SMC3 UBA52(1-76) PSMD9 CKS1B UBC(533-608) UBC(533-608) CDKN1A MNAT1 Cohesin:PDS5:WAPAL:Chromosomal ArmPSMD7 STAG1 CDK2 Ac-Cohesin:PDS5:WAPAL:CentromereSKP1 PSMD5 CDK4 PSMD10 STAG2 WAPAL CCNE2 PSMB9 p-T309,S474-AKT2 CCNA2 Pi2xAcK-SMC3 STAG1 PSMC2 p-T160-CDK2 CDC25A geneWAPAL PSMD10 p-T187-CDKN1B STAG1 ATPUBC(609-684) PDS5B CCND1:CDK4STAG1 CDKN1B PSMD13 PSMC5 PSMB11 CCNA:CDK2p-T308,S473-AKT1 CCNA:CDK2UBC(77-152) CDK2 SHFM1 CCNE2 p-S130-CDKN1A CCNA1 UBB(77-152) UBC(609-684) RPS27A(1-76) RPS27A(1-76) CKS1BCCNA1 RBBP4 STAG1 p-Y88-CDKN1B CUL1 CDC25A gene PDS5B p-FZR1,p-RB1UBC(1-76) p-S795-RB1 PSMA5 p-T286-CCND1 CDCA5PSMA1 2xAcK-SMC3 UBC(1-76) PSMB6 p-Y342-PTK6CCNAMYC:MAX:CDC25A geneRAD21 CCNE1 UBC(77-152) SKP2 Synthesis of DNAPSMB8 CUL1 UBC(1-76) CCNA1 CCND1 UBA52(1-76) CDK7 CDKN1BMYC CyclinE/A:p-T160-CDK2:p-S130-CDKN1A,p-T187-CDKN1BCyclinA:Cdk2:p21/p27complexp-Y342-PTK6 CDC25A gene CCNA1 Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmCCND1 UBC(457-532) UBB(77-152) p-FZR1 Cdc25 A/BPSMC3 STAG2 ATPUBC(77-152) UBA52(1-76) UBB(1-76) UBC(457-532) SMC3 CCND1 PSME1 ATPUBC(153-228) PSMA3 ADPATPSHFM1 PSMD14 UbUBB(153-228) p-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))SMC1A CDK2 CDK4 CDKN1Ap-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))PSMB8 STAG1 PSMB2 PSMA6 CCNH CDK4 PDS5A p-T187-CDKN1B CUL1 p-S28-LIN52 CCNA2 CAKSister Chromosomal Arm CCNE1 PSMC6 PSMC6 PSMA5 ADPCCNA1 UBC(229-304) CCNA1 phospho(T286)-CyclinD1:Cdk4PSME1 STAG2 PSMD13 PDS5A CDCA5 PSMD11 p-T305,S472-AKT3 p-T286-CCND1ESCOUBB(153-228) PSMA3 PSMD1 PSMD6 CCNA2 WEE1DREAM complex:CDC25AgeneCDKN1B:(CDK4:CCND1,(CDK2:CCNE1))CUL1:SKP1:SKP2CCNA2 PSMA2 UBC(381-456) PSMB4 Ac-CoAPSMC1 CDKN1A,CDKN1BCCNA2 p-T-CDKN1A/BSister Centromerep-S130-CDKN1A CCNA2 PSMA7 WAPAL PSMD14 CDKN1B ATPUBB(153-228) PSMD5 TFDP2 PSMA8 CCNE2 UBC(229-304) E2F1 SKP2 PDS5A CDC25B UBC(1-76) ADPPSMC1 PSMC4 PSMD12 Sister Chromosomal Arm UBC(229-304) PSME2 CCNE1 UBC(305-380) 26S proteasomeCDC25A CCNA1 UBB(153-228) UBC(381-456) CDKN1B CDK2 PSMD2 PSMD1 SMC1A E2F5 E2F4 PDS5B p-T160-CDK2 UBC(153-228) FZR1,p-S795-RB1PSMD4 RBL2 SisterCentromeres:Ac-Cohesin:PDS5:CDCA5:WAPALUBC(153-228) p-T187-CDKN1B ATPPSMD2 PSMC4 CDK4 CCNA2 p-T286-CCND1FZR1 SMC1A E2F1:TFDP1,TFDP2:CDC25A geneSister Chromosomal Arm PSME3 CyclinE/A:p-T160-CDK2:CDKN1A,CDKN1BCCNA2 CDKN1B PSMD12 CCNE1 SKP1 PSMB2 RPS27A(1-76) UBB(1-76) CKS1B RAD21 MitoticTelophase/CytokinesisPSMC5 CCNE1 PSMA4 PSMA7 CDK2 UBC(457-532) CCNA:p-T160-CDK2,CCNE:p-T160-CDK2ESCO2 SisterChromosomalArms:Ac-Cohesin:PDS5:CDCA5:WAPALUBC(533-608) CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BUbiquitin ligasePSMD7 UBC(77-152) UBC(305-380) PSMD8 CDCA5 CDKN1B UBC(457-532) PSMF1 UBC(305-380) PSMB3 MAX p-S130-CDKN1A CDKN1A PDS5A PSMB7 p-T286-CCND1 UBC(533-608) SKP2 GSK3BSMC1A CCNA2 PSMB4 TFDP1 UbPSMD3 PSMB5 p-T,p-S-AKTADPPSMF1 CCNA1 ATPPSME4 UBB(1-76) p-T145-CDKN1A UBB(77-152) 26S proteasomep-T160-CDK2 CDKN1A CCNA1 ESCO1 CCNA:p-Y15-CDK2ADPPDS5B RAD21 SMC1A CDK2p-S130-CDKN1A PSMB1 p-T160-CDK2 CDKN1B STAG2 PSMD11 CCNA1 p-T286-CCND1 PSMB5 PSMA1 phospho(T286)-CyclinD1:Cdk4CCNE2 Mitotic PrometaphaseCDC25A gene CyclinA:Cdk2:phospho-p27/p21 complexSMC3 UBC(153-228) UBB(77-152) PSMB1 ADPp-Y15-CDK2 TFDP2 CoA-SHCCND1 CDKN1A CCNA2 ADPCDK2 UBC(381-456) PSMB10 p-T157-CDKN1B p-T160-CDK2 TFDP1 PSMD8 RPS27A(1-76) SMC1A UBC(305-380) CDK4 RAD21 PSMB9 PDS5B PSMA6 SKP1 H2OPSMC3 CABLES1PSMA2 CCNE1 2xAcK-SMC3 CDK2 Sister Centromere PDS5A 14, 343611, 173615142914, 34143720


Description

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.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 69242
Reactome-version 
Reactome version: 65

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Quality Tags

Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  7. 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
  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. Gu Y, Rosenblatt J, Morgan DO.; ''Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.''; PubMed Europe PMC Scholia
  10. 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
  11. 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
  12. 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
  13. Orend G, Hunter T, Ruoslahti E.; ''Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells.''; PubMed Europe PMC Scholia
  14. Van Den Berg DJ, Francke U.; ''Roberts syndrome: a review of 100 cases and a new rating system for severity.''; PubMed Europe PMC Scholia
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Bembenek J, Yu H.; ''Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a.''; PubMed Europe PMC Scholia
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  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. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. Hou F, Zou H.; ''Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion.''; PubMed Europe PMC Scholia
  38. 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
  39. Carrano AC, Eytan E, Hershko A, Pagano M.; ''SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.''; PubMed Europe PMC Scholia
  40. 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
  41. Galaktionov K, Chen X, Beach D.; ''Cdc25 cell-cycle phosphatase as a target of c-myc.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
118522view10:10, 28 May 2021EweitzOntology Term : 'S phase pathway' added !
115059view17:00, 25 January 2021ReactomeTeamReactome version 75
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

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-177750 (Reactome)
26S proteasomeComplexR-HSA-68819 (Reactome)
2xAcK-SMC3 ProteinQ9UQE7 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (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)
Cyclin

A:Cdk2:p21/p27

complex
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:18367 (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)
Sister

Chromosomal

Arms:Ac-Cohesin:PDS5:CDCA5:WAPAL
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)
multi-ubiquitinated

phospho-(T286)

Cyclin D1
ComplexR-HSA-177997 (Reactome)
p-FZR1 ProteinQ9UM11 (Uniprot-TrEMBL)
p-FZR1,p-RB1ComplexR-HSA-187920 (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-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)
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)
CUL1:SKP1:SKP2R-HSA-187545 (Reactome)
Cdc25 A/Bmim-catalysisR-HSA-174110 (Reactome)
CoA-SHArrowR-HSA-2468039 (Reactome)
CoA-SHArrowR-HSA-2473152 (Reactome)
Cohesin:PDS5:WAPAL:CentromereR-HSA-2473152 (Reactome)
Cohesin:PDS5:WAPAL:Chromosomal ArmR-HSA-2468039 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
ArrowR-HSA-187934 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
R-HSA-187916 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
mim-catalysisR-HSA-187916 (Reactome)
Cyclin A:Cdk2:phospho-p27/p21 complexArrowR-HSA-187916 (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: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-CDKN1B:CUL1:SKP1:SKP2:CKS1Bmim-catalysisR-HSA-187575 (Reactome)
Cyclin E/A:p-T160-CDK2:CDKN1A,CDKN1BR-HSA-187520 (Reactome)
Cyclin E/A:p-T160-CDK2:CDKN1A,CDKN1Bmim-catalysisR-HSA-187520 (Reactome)
Cyclin E/A:p-T160-CDK2:p-S130-CDKN1A,p-T187-CDKN1BArrowR-HSA-187520 (Reactome)
Cyclin E/A:p-T160-CDK2:p-S130-CDKN1A,p-T187-CDKN1BR-HSA-187552 (Reactome)
DREAM complex:CDC25A geneTBarR-HSA-188345 (Reactome)
E2F1:TFDP1,TFDP2:CDC25A geneArrowR-HSA-188345 (Reactome)
ESCOmim-catalysisR-HSA-2468039 (Reactome)
ESCOmim-catalysisR-HSA-2473152 (Reactome)
FZR1,p-S795-RB1R-HSA-187948 (Reactome)
GSK3Bmim-catalysisR-HSA-75820 (Reactome)
H2OR-HSA-174110 (Reactome)
MYC:MAX:CDC25A geneArrowR-HSA-188345 (Reactome)
PiArrowR-HSA-174110 (Reactome)
R-HSA-174054 (Reactome) During G1 phase of the cell cycle, cyclin A is synthesized and associates with Cdk2.
R-HSA-174110 (Reactome) Cdc25A, and probably Cdc25B, regulate the entry into S phase cell cycle by removing inhibitory phosphates from the Cdk2 subunit of Cyclin A:Cdk2.
R-HSA-174164 (Reactome) The CDK activity of the Cyclin A:Cdk2 complex is inhibited by phosphorylation at Tyr-15 by the WEE1 kinase (Gu et al. 1992, Wu et al. 2001). WEE1-mediated phosphorylation of cyclin A-bound CDK2 is positively regulated by CABLES1 (Wu et al. 2001).
R-HSA-174273 (Reactome) After forming in the cytoplasm, the Cyclin A:Cdk2 complexes are translocated to the nucleus.
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-187916 (Reactome) Recognition of p27 by SCF(Skp2) and the subsequent ubiquitination of p27 is dependent upon Cyclin E/A:Cdk2-mediated phosphorylation of p27 at Thr 187 (Montagnoli et al., 1999). p21 is also phosphorylated at a specific site (Ser130) by Cyclin E/A:Cdk2, stimulating its ubiquitination. Unlike p27, however, p21 ubiquitination can take place in the absence of phosphorylation, although with less efficiency (Bornstein et al.,2003).
R-HSA-187934 (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 (Guardavaccaro and Pagano, 2006).
R-HSA-187948 (Reactome) Active Cyclin A:Cdk2 complexes phosphorylate and inactivate proteins required for maintaining the G1/S phase including. In addition to CDKN1A and CDKN1B, the active CCNA:p-T160-CDK2 complex also phosphorylates FZR1 (Cdh1) and RB1. All this creates auto-amplification loops that render Cdk2 increasingly more active. In G2, Cdk2, in association with cyclin A, phosphorylates E2F1 and E2F3 resulting in the inactivation and possibly degradation of these two transcription factors (Dynlacht et al., 1994; Krek et al., 1994).
R-HSA-187949 (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-188345 (Reactome) Binding of the MYC:MAX heterodimer to MYC response elements in the first and second intron of the CDC25A gene activates CDC25A transcription in mid to late G1 (Galaktionov et al. 1996).
Transcription of the CDC25A gene can be directly activated by E2F1 (DeGregori et al. 1995, Vigo et al. 1999).
Transcription of the CDC25A gene is directly inhibited by the DREAM complex (Litovchick et al. 2007).
R-HSA-198613 (Reactome) Phosphorylation of p27Kip1 at T157 and of p21Cip1 at T145 by AKT leads to their retention in the cytoplasm, segregating these cyclin-dependent kinase (CDK) inhibitors from cyclin-CDK complexes.
R-HSA-2468039 (Reactome) Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. These dual acetylations on SMC3 are deacetylated by HDAC8 after the cohesin removal from chromatin for the dissociation and recycling of cohesin subunits (Deardorff et al. 2012). ESCO1 and ESCO2 differ in their N-termini, which are necessary for chromatin binding, and may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005), as suggested by the study of Esco2 knockout mice (Whelan et al. 2012).
R-HSA-2468041 (Reactome) CDCA5 (Sororin) is essential for the establishment of sister chromatid cohesion in mammalian cells (Rankin et al. 2005) in the S-phase of the cell cycle (Nishiyama et al. 2010). Several factors contribute to the recruitment of CDCA5 to chromatin-associated cohesin: DNA replication (i.e. presence of two sister chromatids), association of cohesin complex with PDS5, and acetylation of the SMC3 cohesin subunit by ESCO1/ESCO2 acetyltransferases. Experiments in which a recombinant tagged mouse CDCA5 was expressed in human HeLa cell line showed that CDCA5 starts to accumulate on chromatin in S-phase and dissociates from chromosomal arms in prophase (Nishiyama et al. 2010).

CDCA5 is essential for the establishment of chromosomal cohesion only in the presence of WAPAL, suggesting that the key role of CDCA5 (Sororin) is to antagonize WAPAL. Both CDCA5 and WAPAL contain an FGF (phenylalanine-glycine-phenylalanine) motif that is essential for PDS5 binding and is also essential for CDCA5 function in cohesion establishment. Indeed, CDCA5 is able to displace WAPAL from PDS5:WAPAL heterodimers in vitro. In vivo experiments in Xenopus egg extracts suggest that CDCA5 rearranges the topology of cohesin associated proteins so that WAPAL is no longer able to inhibit sister chromatid cohesion but remains associated with cohesin (Nishiyama et al. 2010).
R-HSA-2473151 (Reactome) CDCA5 (Sororin) is essential for the establishment of sister chromatid cohesion at centromeres. Experiments in which a recombinant tagged mouse CDCA5 was expressed in human HeLa cell line showed that CDCA5 starts to accumulate on chromatin in S-phase and dissociates from centromeres in anaphase (Nishiyama et al. 2010).
R-HSA-2473152 (Reactome) Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. Divergent N-termini of ESCO1 and ESCO2, necessary for chromatin binding, suggest that ESCO1 and ESCO2 may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005). Several studies suggest that ESCO2 may be predominantly involved in acetylation of the SMC3 subunit of centromeric cohesin. A conditional targeting of Esco2 locus in mice leads to pre-implantational loss of homozygous Esco2 -/- embryos at the eight-cell stage. Prometaphase chromosomes isolated from two-cell stage Esco2 knockout embryos show marked cohesion defect at centromeres (Whelan et al. 2012). ESCO2 protein appears in the S-phase (Hou and Zou 2005, Whelan et al. 2012) and in mouse embryonic fibroblasts Esco2 predominantly localizes to pericentric heterochromatin (Whelan et al. 2012). Mutations in the ESCO2 gene (Vega et al. 2005) that impair ESCO2 acetyltransferase activity (Gordillo et al. 2008) are the cause of the Roberts syndrome, an autosomal recessive disorder characterized by craniofacial and limb abnormalities, and intellectual disability. Metaphase chromosomes of Roberts syndrome patients exhibit loss of cohesion at heterochromatic regions of centromeres and the Y chromosome, with a characteristic 'railroad track appearance' (Van den Berg and Francke 1993, Vega et al. 2005).
R-HSA-75820 (Reactome) At the beginning of this reaction, 1 molecule of 'Cyclin D1:Cdk4', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'phospho(T286)-Cyclin D1:Cdk4', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'glycogen synthase kinase-3 beta'.

R-HSA-75822 (Reactome) In this reaction, 1 molecule of 'phospho(T286)-Cyclin D1:Cdk4' is translocated from nucleoplasm to cytosol.

This reaction takes place in the 'nuclear envelope' (Dhiel et al.1994).

R-HSA-75823 (Reactome) In this reaction, 1 molecule of 'phospho(T286)-Cyclin D1' is translocated from nucleoplasm to cytosol.

This reaction takes place in the 'nuclear envelope' (Diehl et al. 1997).

R-HSA-75824 (Reactome) Cyclin D is targeted for degradation by multi-ubiquitination.
R-HSA-75825 (Reactome) Phosphorylated Cyclin D1 is degraded during S phase by the 26S proteasome allowing for efficient DNA synthesis.
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).
Sister Centromeres:Ac-Cohesin:PDS5:CDCA5:WAPALArrowR-HSA-2473151 (Reactome)
Sister

Chromosomal

Arms:Ac-Cohesin:PDS5:CDCA5:WAPAL
ArrowR-HSA-2468041 (Reactome)
Sister CentromereR-HSA-2473151 (Reactome)
Sister Chromosomal ArmR-HSA-2468041 (Reactome)
UbArrowR-HSA-187574 (Reactome)
UbArrowR-HSA-75825 (Reactome)
UbR-HSA-187575 (Reactome)
UbR-HSA-75824 (Reactome)
Ubiquitin ligasemim-catalysisR-HSA-75824 (Reactome)
WEE1mim-catalysisR-HSA-174164 (Reactome)
multi-ubiquitinated

phospho-(T286)

Cyclin D1
ArrowR-HSA-75824 (Reactome)
multi-ubiquitinated

phospho-(T286)

Cyclin D1
R-HSA-75825 (Reactome)
p-FZR1,p-RB1ArrowR-HSA-187948 (Reactome)
p-T,p-S-AKTmim-catalysisR-HSA-198613 (Reactome)
p-T-CDKN1A/BArrowR-HSA-198613 (Reactome)
p-T286-CCND1ArrowR-HSA-75823 (Reactome)
p-T286-CCND1R-HSA-75823 (Reactome)
p-T286-CCND1R-HSA-75824 (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)
phospho(T286)-Cyclin D1:Cdk4ArrowR-HSA-75820 (Reactome)
phospho(T286)-Cyclin D1:Cdk4ArrowR-HSA-75822 (Reactome)
phospho(T286)-Cyclin D1:Cdk4R-HSA-75822 (Reactome)
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