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.
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 Human Ortholog: 22q12.1
Cellular Component:  Golgi apparatus; nucleoplasm; PML body
Molecular Function:  ATP binding; identical protein binding; kinase activity; metal ion binding; protein binding; protein homodimerization activity; protein kinase binding; protein serine/threonine kinase activity; ubiquitin protein ligase binding
Biological Process:  cell division; cellular protein catabolic process; cellular response to bisphenol A; cellular response to DNA damage stimulus; cellular response to gamma radiation; DNA damage checkpoint; DNA damage induced protein phosphorylation; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; 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 spindle assembly; negative regulation of cell cycle arrest; negative regulation of DNA damage checkpoint; peptidyl-serine phosphorylation; positive regulation of anoikis; positive regulation of protein phosphorylation; positive regulation of transcription, DNA-templated; protein autophosphorylation; protein phosphorylation; protein stabilization; regulation of protein catabolic process; regulation of signal transduction by p53 class mediator; regulation of transcription, DNA-templated; replicative cell aging; replicative senescence; response to glycoside; signal transduction in response to DNA damage; signal transduction involved in intra-S DNA damage checkpoint
Disease: Breast Cancer; Li-fraumeni Syndrome 2; Osteogenic Sarcoma; Prostate Cancer
Reference #:  O96017 (UniProtKB)
Alt. Names/Synonyms: Cds1; checkpoint-like protein CHK2; CHEK2; CHK2; CHK2 checkpoint homolog (S. pombe); HuCds1; LFS2; PP1425; protein kinase CHK2; RAD53; Serine/threonine-protein kinase Chk2
Gene Symbols: CHEK2
Molecular weight: 60,915 Da
Basal Isoelectric point: 5.65  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  G1/S Checkpoint  |  G2/M DNA Damage Checkpoint
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Chk2

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