CHEK1 - Serine/threonine-protein kinase Chk1 - human protein (Function)
 
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CHEK1 »  Serine/threonine-protein kinase Chk1   [ EC 2.7.11.1 ]
 
Protein also known as:  Cell cycle checkpoint kinase.
Gene name:  CHEK1
Entry whose protein(s) existence is based on evidence at protein level
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1 438 3
GENE REF ISO

Function

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Overview 
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.  
1
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Histone kinase activity (H3-T11 specific)definition[GO:0035402]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
15
  • IntAct
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • UniProtKB
GO biological process 
Cellular response to caffeinedefinition[GO:0071313] silver  
1
  • Ortholog Compara
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • UniProtKB
Cellular response to mechanical stimulusdefinition[GO:0071260]  
1
  • UniProtKB
Chromatin-mediated maintenance of transcriptiondefinition[GO:0048096]  
1
  • Ortholog Curator
DNA damage checkpointdefinition[GO:0000077]  
2
  • UniProtKB
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
1
  • UniProtKB
DNA repairdefinition[GO:0006281]  
1
  • UniProtKB
G2 DNA damage checkpointdefinition[GO:0031572]  
1
  • UniProtKB
G2/M transition of mitotic cell cycledefinition[GO:0000086] silver  
1
  • Ortholog Compara
Histone H3-T11 phosphorylationdefinition[GO:0035407] silver  
1
  • Ortholog Compara
Negative regulation of DNA biosynthetic processdefinition[GO:2000279] silver  
1
  • Ortholog Compara
Negative regulation of G2/M transition of mitotic cell cycledefinition[GO:0010972] silver  
1
  • Ortholog Compara
Negative regulation of mitosisdefinition[GO:0045839]  
1
  • UniProtKB
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127] silver  
1
  • Ortholog Compara
Regulation of double-strand break repair via homologous recombinationdefinition[GO:0010569]  
1
  • UniProtKB
Regulation of histone H3-K9 acetylationdefinition[GO:2000615]  
1
  • Ortholog Curator
Regulation of mitotic centrosome separationdefinition[GO:0046602]  
1
  • UniProtKB
Regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damagedefinition[GO:0010767]  
1
  • Ortholog Curator
Replicative senescencedefinition[GO:0090399]  
1
  • BHF-UCL
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 is regulated in the following manner
Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication. Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B.  
1
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+1111  
HTLV-I infection  hsa05166+1111  
p53 signaling pathway  hsa04115+1111  
According to Reactome, this protein belongs to the following pathways:
Activation of ATR in response to replication stress  REACT_6769  
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex  REACT_407  
G2/M DNA damage checkpoint  REACT_897  
Signaling by SCF-KIT  REACT_111040  
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A  REACT_1614  
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
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: CHEK1
GenomeRNAi: 1111
PRO: PR:O14757
Chemistry
GuidetoPHARMACOLOGY: 1987