CHEK2 - Serine/threonine-protein kinase Chk2 - human protein (Function)
 
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CHEK2 »  Serine/threonine-protein kinase Chk2   [ EC 2.7.11.1 ]
 
Protein also known as:  CHK2 checkpoint homolog.
Gene name:  CHEK2
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 417 13
GENE REF ISO

Function

 show evidences
Overview 
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.  
18
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
2
  • IntAct
Metal ion bindingdefinition[GO:0046872]  
1
  • UniProtKB KW
Protein bindingdefinition[GO:0005515]  
12
  • UniProtKB
  • IntAct
Protein homodimerization activitydefinition[GO:0042803]  
1
  • UniProtKB
Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
3
  • UniProtKB
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
GO biological process 
Cell divisiondefinition[GO:0051301]  
1
  • UniProtKB KW
Cellular protein catabolic processdefinition[GO:0044257]  
1
  • UniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
3
  • UniProtKB
DNA damage checkpointdefinition[GO:0000077]  
2
  • UniProtKB
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
1
  • UniProtKB
Double-strand break repairdefinition[GO:0006302]  
1
  • UniProtKB
G2/M transition of mitotic cell cycledefinition[GO:0000086]  
1
  • UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
3
  • UniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
2
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Protein stabilizationdefinition[GO:0050821]  
1
  • UniProtKB
Regulation of protein catabolic processdefinition[GO:0042176]  
1
  • UniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • UniProtKB
Replicative senescencedefinition[GO:0090399]  
1
  • BHF-UCL
Response to gamma radiationdefinition[GO:0010332] silver  
1
  • Ortholog Compara
Signal transduction in response to DNA damagedefinition[GO:0042770]  
1
  • MGI
Signal transduction involved in intra-S DNA damage checkpointdefinition[GO:0072428]  
1
  • UniProtKB
Spindle assembly involved in mitosisdefinition[GO:0090307]  
1
  • UniProtKB
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
1
  • UniProtKB
It is regulated in the following manner
Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68.  
2
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+11200  
HTLV-I infection  hsa05166+11200  
p53 signaling pathway  hsa04115+11200  
According to Reactome, this protein belongs to the following pathways:
G2/M DNA damage checkpoint  REACT_897  
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A  REACT_1614  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Mitosis  definition   [KW-0498]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
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: CHEK2
GenomeRNAi: 11200
PRO: PR:O96017
Chemistry
GuidetoPHARMACOLOGY: 1988
GuidetoPHARMACOLOGY: 2787