CDK1 - Cyclin-dependent kinase 1 - human protein (Function)
 
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CDK1 »  Cyclin-dependent kinase 1
 
Gene name:  CDK1
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Cyclin bindingdefinition[GO:0030332] silver  
  • IEAOrtholog Compara
Cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0004693]  
2
  • IDAUniProtKB
Histone kinase activitydefinition[GO:0035173] silver  
  • IEAOrtholog Compara
Hsp70 protein bindingdefinition[GO:0030544] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
18
  • IPIIntAct
  • IPIBHF-UCL
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • NASPINC
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDAWormBase
RNA polymerase II carboxy-terminal domain kinase activitydefinition[GO:0008353]  
1
  • IDAUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Cell agingdefinition[GO:0007569] silver  
  • IEAOrtholog Compara
Cell migrationdefinition[GO:0016477]  
1
  • TASUniProtKB
Cellular response to hydrogen peroxidedefinition[GO:0070301] silver  
  • IEAOrtholog Compara
Centrosome cycledefinition[GO:0007098]  
1
  • TASUniProtKB
Chromosome condensationdefinition[GO:0030261] silver  
  • IEAOrtholog Compara
DNA repairdefinition[GO:0006281]  
1
  • TASUniProtKB
DNA replicationdefinition[GO:0006260]  
1
  • TASUniProtKB
Epithelial cell differentiationdefinition[GO:0030855]  
1
  • IEPUniProtKB
Histone phosphorylationdefinition[GO:0016572] silver  
  • IEAOrtholog Compara
Microtubule cytoskeleton organizationdefinition[GO:0000226]  
1
  • TASUniProtKB
Mitotic G2 DNA damage checkpointdefinition[GO:0007095] silver  
  • IEAOrtholog Compara
Mitotic nuclear divisiondefinition[GO:0007067]  
  • IEAUniProtKB KW
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IDAUniProtKB
Organ regenerationdefinition[GO:0031100] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDAWormBase
Positive regulation of cardiac muscle cell proliferationdefinition[GO:0060045] silver  
  • IEAOrtholog Compara
Positive regulation of DNA replicationdefinition[GO:0045740] silver  
  • IEAOrtholog Compara
Positive regulation of gene expressiondefinition[GO:0010628] silver  
  • IEAOrtholog Compara
Positive regulation of mitotic cell cycledefinition[GO:0045931] silver  
  • IEAOrtholog Compara
Positive regulation of protein import into nucleus, translocationdefinition[GO:0033160] silver  
  • IEAOrtholog Compara
Pronuclear fusiondefinition[GO:0007344]  
1
  • TASUniProtKB
Protein complex assemblydefinition[GO:0006461] silver  
  • IEAOrtholog Compara
Protein localization to kinetochoredefinition[GO:0034501]  
1
  • IDABHF-UCL
Regulation of embryonic developmentdefinition[GO:0045995]  
1
  • TASUniProtKB
Regulation of Schwann cell differentiationdefinition[GO:0014038]  
1
  • TASUniProtKB
Response to activitydefinition[GO:0014823] silver  
  • IEAOrtholog Compara
Response to aminedefinition[GO:0014075] silver  
  • IEAOrtholog Compara
Response to axon injurydefinition[GO:0048678] silver  
  • IEAOrtholog Compara
Response to cadmium iondefinition[GO:0046686] silver  
  • IEAOrtholog Compara
Response to copper iondefinition[GO:0046688] silver  
  • IEAOrtholog Compara
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to ethanoldefinition[GO:0045471] silver  
  • IEAOrtholog Compara
Response to organic cyclic compounddefinition[GO:0014070] silver  
  • IEAOrtholog Compara
Response to toxic substancedefinition[GO:0009636] silver  
  • IEAOrtholog Compara
Ventricular cardiac muscle cell developmentdefinition[GO:0055015] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.22: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
EC 2.7.11.23: ATP + [DNA-directed RNA polymerase] ADP + [DNA-directed RNA polymerase] phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it. Activated through a multistep process; binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus, activated by CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15. Inhibited by flavopiridol and derivatives, pyrimidine derivatives, pyridine derivatives, purine derivatives, staurosporine, paullones, oxoindoles, indazole analogs, indolin-2-ones, pyrazolo[3,4-b]pyridines, imidazo[1,2-a]pyridine (AZ703), thiazolinone analogs(RO-3306), thiazol urea, macrocyclic quinoxalin-2-one, pyrrolo[2,3-a]carbazole, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine (Dinaciclib, SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00, R547/Ro-4584820 and SNS-032/BMS-387032. Repressed by the CDK inhibitors CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the G1-S checkpoint upon DNA damage. Transient activation by rapid and transient dephosphorylation at Tyr-15 triggered by TGFB1.  
2
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+983  
Gap junction  hsa04540+983  
Herpes simplex infection  hsa05168+983  
Oocyte meiosis  hsa04114+983  
p53 signaling pathway  hsa04115+983  
Progesterone-mediated oocyte maturation  hsa04914+983  
According to Reactome, this protein belongs to the following pathways:
Activation of NIMA Kinases NEK9, NEK6, NEK7  REACT_160122  
APC/C:Cdc20 mediated degradation of Cyclin B  REACT_6820  
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex  REACT_407  
Condensation of Prometaphase Chromosomes  REACT_150260  
Condensation of Prophase Chromosomes  REACT_172744  
Cyclin A/B1 associated events during G2/M transition  REACT_1857  
Cyclin B2 mediated events  REACT_2101  
Depolymerisation of the Nuclear Lamina  REACT_200828  
E2F mediated regulation of DNA replication  REACT_471  
E2F-enabled inhibition of pre-replication complex formation  REACT_1321  
ERK1 activation  REACT_1391  
G0 and Early G1  REACT_111214  
G1/S-Specific Transcription  REACT_683  
G2/M DNA replication checkpoint  REACT_1846  
Golgi Cisternae Pericentriolar Stack Reorganization  REACT_1100  
Loss of Nlp from mitotic centrosomes  REACT_15364  
Loss of proteins required for interphase microtubule organization from the centrosome  REACT_15451  
MASTL Facilitates Mitotic Progression  REACT_150182  
Nuclear Pore Complex (NPC) Disassembly  REACT_163931  
Phosphorylation of Emi1  REACT_6875  
Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes  REACT_6362  
Phosphorylation of the APC/C  REACT_6904  
Recruitment of mitotic centrosome proteins and complexes  REACT_15296  
Recruitment of NuMA to mitotic centrosomes  REACT_15510  
Regulation of APC/C activators between G1/S and early anaphase  REACT_6837  
Regulation of PLK1 Activity at G2/M Transition  REACT_160315  
Resolution of Sister Chromatid Cohesion  REACT_150425  
Note 
As a key regulator of the cell cycle, CDK1 is a potent therapeutic target for inhibitors in cancer treatment (PubMed21517772).  
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  • CuratedUniProtKB
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
Mitosis  definition   [KW-0498]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Cyclin-dependent_kinase_1
GeneWiki: Cdk1
GenomeRNAi: 983
PRO: PR:P06493
Chemistry
GuidetoPHARMACOLOGY: 1961