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Chk2
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. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily. High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues. 13 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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| Protein type: CAMK group; EC 2.7.11.1; Kinase, protein; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); RAD53 family; Tumor suppressor |
| Chromosomal Location of rat Ortholog: 12q16 |
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Cellular Component:
chromosome, telomeric region; cytoplasm; Golgi apparatus; nucleoplasm; nucleus; PML body
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Molecular Function:
ATP binding; identical protein binding; kinase activity; protein binding; protein homodimerization activity; protein kinase activity; protein kinase binding; protein serine/threonine kinase activity; ubiquitin protein ligase binding
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Biological Process:
cellular response to bisphenol A; cellular response to gamma radiation; cellular response to xenobiotic stimulus; DNA damage checkpoint signaling; DNA damage response; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; double-strand break repair; G2/M transition of mitotic cell cycle; intrinsic apoptotic signaling pathway in response to DNA damage; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; mitotic DNA damage checkpoint signaling; mitotic intra-S DNA damage checkpoint signaling; mitotic spindle assembly; negative regulation of DNA damage checkpoint; peptidyl-serine phosphorylation; positive regulation of anoikis; positive regulation of DNA-templated transcription; positive regulation of protein phosphorylation; protein autophosphorylation; protein catabolic process; protein phosphorylation; protein stabilization; regulation of DNA-templated transcription; regulation of protein catabolic process; response to gamma radiation; response to glycoside; signal transduction in response to DNA damage; thymocyte apoptotic process
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Reference #:
Q9R019
(UniProtKB)
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Alt. Names/Synonyms: Checkpoint kinase Chk2; Chek2; Chk2; CHK2 checkpoint homolog (S. pombe); CHK2 checkpoint homolog (S. pombe), isoform CRA_a; protein kinase Chk2; Rad53
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Gene Symbols: Chek2
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Molecular weight:
60,930 Da
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Basal Isoelectric point:
6.06
Predict pI for various phosphorylation states
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CST Pathways:
Apoptosis Regulation
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G1/S Checkpoint
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G2/M DNA Damage Checkpoint
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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