CDK2 - Cyclin-dependent kinase 2 - human protein (Function)
 
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CDK2 »  Cyclin-dependent kinase 2   [ EC 2.7.11.22 ]
 
Protein also known as:  Cell division protein kinase 2.
Gene name:  CDK2
Entry whose protein(s) existence is based on evidence at protein level
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1 530 2
GENE REF ISO

Function

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Overview 
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.  
17
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Cyclin bindingdefinition[GO:0030332]  
1
  • IDAUniProtKB
Cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0004693]  
1
  • IDAUniProtKB
Contributes to histone kinase activitydefinition[GO:0035173]  
1
  • IDAUniProtKB
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
38
  • IPIIntAct
  • IPIUniProtKB
  • IPIHGNC
GO biological process 
Cellular response to nitric oxidedefinition[GO:0071732]  
1
  • TASUniProtKB
Centrosome duplicationdefinition[GO:0051298]  
1
  • TASUniProtKB
DNA repairdefinition[GO:0006281]  
  • IEAUniProtKB KW
DNA replicationdefinition[GO:0006260]  
1
  • TASUniProtKB
G2/M transition of mitotic cell cycledefinition[GO:0000086]  
1
  • NASUniProtKB
Histone phosphorylationdefinition[GO:0016572]  
1
  • IDAGOC
Meiotic nuclear divisiondefinition[GO:0007126]  
1
  • TASUniProtKB
Mitotic G1 DNA damage checkpointdefinition[GO:0031571]  
1
  • TASUniProtKB
Mitotic nuclear divisiondefinition[GO:0007067]  
  • IEAUniProtKB KW
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • IDAUniProtKB
Positive regulation of DNA-dependent DNA replication initiationdefinition[GO:0032298] silver  
  • IEAOrtholog Compara
Positive regulation of transcription, DNA-templateddefinition[GO:0045893] silver  
  • IEAOrtholog Compara
Potassium ion transportdefinition[GO:0006813] silver  
  • IEAOrtholog Compara
Ras protein signal transductiondefinition[GO:0007265]  
1
  • IEPBHF-UCL
Regulation of gene silencingdefinition[GO:0060968]  
1
  • IDAUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.22: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21).  
3
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+1017  
Herpes simplex infection  hsa05168+1017  
Measles  hsa05162+1017  
Oocyte meiosis  hsa04114+1017  
p53 signaling pathway  hsa04115+1017  
Pathways in cancer  hsa05200+1017  
Progesterone-mediated oocyte maturation  hsa04914+1017  
Prostate cancer  hsa05215+1017  
Small cell lung cancer  hsa05222+1017  
According to Reactome, this protein belongs to the following pathways:
Activation of ATR in response to replication stress  REACT_6769  
Activation of the pre-replicative complex  REACT_1095  
CDK-mediated phosphorylation and removal of Cdc6  REACT_1221  
Cyclin A/B1 associated events during G2/M transition  REACT_1857  
Cyclin A:Cdk2-associated events at S phase entry  REACT_9029  
DNA Damage/Telomere Stress Induced Senescence  REACT_169185  
Factors involved in megakaryocyte development and platelet production  REACT_24970  
G0 and Early G1  REACT_111214  
G2 Phase  REACT_1915  
Meiotic recombination  REACT_27271  
Orc1 removal from chromatin  REACT_1156  
p53-Dependent G1 DNA Damage Response  REACT_1625  
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes  REACT_308  
Regulation of APC/C activators between G1/S and early anaphase  REACT_6837  
SCF(Skp2)-mediated degradation of p27/p21  REACT_9003  
Senescence-Associated Secretory Phenotype (SASP)  REACT_169168  
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Meiosis  definition   [KW-0469]
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_2
GenomeRNAi: 1017
PRO: PR:P24941
Chemistry
GuidetoPHARMACOLOGY: 1973