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Chk2 a CAMK protein kinase of the Rad53 family. A cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. Phosphorylates and inhibits CDC25C, preventing entry into mitosis, p53, leading to cell cycle arrest in G1, and BRCA1, restoring survival after DNA damage. Twelve splice variant isoforms have been described for human Chk2. LOF mutants cause Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype also caused by p53 mutations. Familial mutations also associated with prostate and breast cancer, and mutations also seen in a variety of sporadic cancers and cell lines. Note: This description may include information from UniProtKB.
Protein type: CAMK group; EC; Kinase, protein; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); RAD53 family; Tumor suppressor
Chromosomal Location of Human Ortholog: 22q12.1
Cellular Component: chromosome, telomeric region; Golgi apparatus; nucleoplasm; PML body
Molecular Function: identical protein binding; protein binding; protein homodimerization activity; protein kinase binding; protein serine/threonine kinase activity; ubiquitin protein ligase binding
Biological Process: cellular protein catabolic process; DNA damage checkpoint; DNA damage induced protein phosphorylation; DNA damage response, signal transduction; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; DNA damage response, signal transduction resulting in induction of apoptosis; double-strand break repair; G2/M transition of mitotic cell cycle; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of transcription, DNA-dependent; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein stabilization; regulation of apoptosis; regulation of protein catabolic process; regulation of transcription, DNA-dependent; replicative cell aging; response to DNA damage stimulus
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
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