S Phase (Homo sapiens)

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311183, 11, 14, 22, 26...4, 29, 35, 411238132, 4022717, 389, 105, 25, 395, 275, 19, 25, 33723, 3427825, 395, 212412, 11, 16, 26, 37133025, 27, 28, 32nucleoplasmcytosolPDS5A CDK4 p-T160-CDK2 CCNA2 CyclinE/A:p-T160-CDK2:CDKN1A,CDKN1Bp-T305,S472-AKT3 CCNA2 CCNE1 CCNE1 CCNA2 PDS5B p-T187-CDKN1B PSME4 SisterChromosomalArms:Ac-Cohesin:PDS5:CDCA5:WAPALADPCCNA1 PSMC3 UBC(77-152) UBC(77-152) CCNE2 ATP26S proteasomeCCNA1 SKP2 PSMC2 UBC(153-228) CDKN1B PDS5A CDC25B PSMC1 PSME1 PDS5B Cohesin:PDS5:WAPAL:Chromosomal ArmSKP1 CDKN1BPSMD9 PDS5A PSMD4 p-T286-CCND1UbUBC(1-76) SKP2 CDKN1A PDS5B PSMB3 CDKN1B UBA52(1-76) CCNA2 RAD21 CCNA1 CCNA2 UBB(77-152) STAG1 hyperphosphorylated RB1 PSMA3 PSMB6 p-T286-CCND1 CDKN1B PSMD2 Cdc25 A/BCDK2 ATPPSMA6 UBB(77-152) CDCA5 UBC(457-532) PSMD14 STAG2 STAG2 CCNA:p-T160-CDK2,CCNE:p-T160-CDK2PSMD11 CKS1B CDC25A gene PSMB6 CUL1 CKS1B CCND1 Ac-Cohesin:PDS5:WAPAL:CentromerePSMD8 PSMB4 CDKN1A UBC(229-304) CCNE1 WAPAL PSMD6 CoA-SHp-T160-CDK2 UBB(1-76) ATPPDS5B PSMD1 Sister Centromere CDK2 CCNA2 PSMC2 PSMD4 CCND1:CDK4SMC3 MitoticTelophase/CytokinesisUBC(457-532) SHFM1 PSMD12 CyclinA:Cdk2:p21/p27complexWEE1CCNA1 CCNA1 UBC(77-152) CABLES1PSMF1 PSMA5 2xAcK-SMC3 PSMD13 p-T286-CCND1UBC(1-76) RPS27A(1-76) p-Y15-CDK2 UBC(229-304) PDS5A STAG2 CCNA1 WAPAL RPS27A(1-76) PSME3 CDK2 2xAcK-SMC3 E2F1 TFDP2 PSMD11 p-S130-CDKN1A PSMB8 CyclinA:Cdk2:phospho-p27/p21 complexUBA52(1-76) UBC(153-228) ATPCCNA2 PSMA1 PSMA4 CDK4 UBC(229-304) RBBP4 CCNA2 ESCO1 UBC(305-380) CDC25A gene UBC(457-532) ESCOCDC25A PSMD5 CCNACDC25A geneCCNA1 UBC(305-380) PSME2 CCNA:p-T160-CDK2CCNA:CDK2PSMC5 WAPAL CDKN1A,CDKN1Bp-T286-CCND1 ADPRPS27A(1-76) CCNE1 UBC(381-456) PSMA5 phospho(T286)-CyclinD1:Cdk4E2F4 CCNE1 UBC(153-228) CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1BATPCyclinE/A:p-T160-CDK2:p-S130-CDKN1A,p-T187-CDKN1Bp-Y88-CDKN1B PSMB1 MYC PDS5B CCNA2 CKS1BMAX CDKN1Bp-T308,S473-AKT1 Sister Chromosomal Arm CDKN1B UBB(153-228) RAD21 PSMC4 PSMD12 E2F5 CCNA:p-Y15-CDK2UBB(77-152) PSMC4 PSMB10 CAKp-T,p-S-AKTCCNH SKP1 CCNE2 Sister CentromereUBC(381-456) CDK2 Ac-CoAUBA52(1-76) SMC1A CDKN1B UBC(609-684) UBC(1-76) ADPCCNA1 PSME3 CCNA2 UBB(153-228) DREAM complex:CDC25AgeneCDKN1A PSMD14 SKP2 UBB(77-152) RAD21 ATPGSK3BPSMA2 PSME1 WAPAL UBC(305-380) p-Y342-PTK6PSMB11 SKP1 CCNE1 CCND1 p-T309,S474-AKT2 SMC1A LIN37 CDK4 E2F1:TFDP1,TFDP2:CDC25A genep-T160-CDK2 CDC25AMYC:MAX:CDC25A geneLIN9 CDK7 p-T187-CDKN1B SisterCentromeres:Ac-Cohesin:PDS5:CDCA5:WAPALSTAG1 CDCA5UBC(609-684) ADPSister Chromosomal Arm ADPp-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))PSMB2 UBC(609-684) CUL1 PSMC5 PSMF1 PSMD8 p-T160-CDK2 CCNA2 SHFM1 Ubp-T187-CDKN1B UBC(609-684) STAG2 Sister ChromosomalArmp-T286-CCND1 PSMB8 p-T-CDKN1A/BCDK4 WAPAL TFDP2 SKP1 RPS27A(1-76) p-S130-CDKN1A PSMA8 Synthesis of DNACCNA1 PSMB2 PSMD7 PSMD9 PSMB4 SMC1A PSMB9 ADPPSMA6 Sister Centromere 26S proteasomeCDK2 PSMA7 CCNE1 PSMB7 STAG2 UBB(1-76) PSMD2 PSME2 SKP2 CCNA2 WAPAL UBC(229-304) CDCA5 RAD21 CUL1:SKP1:SKP2CCNA1 PSMD3 Ubiquitin ligaseATPPSMD5 CKS1B UBC(153-228) RAD21 CCNE2 UBC(381-456) UBC(533-608) CCND1 UBC(305-380) p-T145-CDKN1A CyclinE/A:CDK2:p-S130-CDKN1A,p-T187-CDKN1B:CUL1:SKP1:SKP2:CKS1B:3xubiquitinp-T187-CDKN1B PSMD10 CDK4 PSMC6 PSMD3 TFDP1 CDKN1B SMC3 PiESCO2 CDKN1A,CDKN1BPSMD7 PSMB3 CUL1 PSMA2 SMC1A CCNE2 SMC1A STAG2 STAG1 phospho(T286)-CyclinD1:Cdk4p-S130-CDKN1A TFDP1 CDKN1AUBC(533-608) LIN54 CCNA:CDK2STAG1 PDS5A CDKN1AUBC(533-608) 2xAcK-SMC3 PSMD6 p-T160-CDK2 p-FZR1 PSMA1 CDK2 PSMA3 PSMB1 CCNA1 ATPPSMB5 p-FZR1,p-RB1CCND1 FZR1,p-S795-RB1UBC(533-608) CUL1 CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))Sister Centromere UBB(153-228) ADPUBC(77-152) RAD21 PSMC1 UBC(457-532) CUL1:SKP1:SKP2:CKS1BCCNA1 UBB(1-76) p-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))PSMB7 STAG1 p-S130-CDKN1A PSMD13 p-S28-LIN52 CDKN1A RBL2 CDK2 UBC(1-76) MNAT1 PSMC3 Cohesin:PDS5:WAPAL:CentromereH2OPSMB5 PDS5A PSMD10 Sister Chromosomal Arm p-T157-CDKN1B ADPUBC(381-456) 2xAcK-SMC3 UBB(1-76) CDK4 Ac-Cohesin:PDS5:WAPAL:Chromosomal Armp-S795-RB1 PSMA7 PSMC6 multi-ubiquitinatedphospho-(T286)Cyclin D1CCNE1 CDC25A gene Mitotic PrometaphaseUBA52(1-76) p-T160-CDK2 PSMB9 CDK2p-Y342-PTK6 STAG1 PDS5B SMC1A PSMB10 PSMD1 CCNE2 UBB(153-228) PSMA4 FZR1 29, 356, 156, 15364383820411515


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: 75

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Quality Tags

Ontology Terms

 

Bibliography

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  20. Bembenek J, Yu H.; ''Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a.''; PubMed Europe PMC Scholia
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  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
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  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: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)
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: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)
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)
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.
multi-ubiquitinated

phospho-(T286)

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)
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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