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.
Protein type: Tumor suppressor; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; Protein kinase, CAMK; EC 2.7.11.1; CAMK group; RAD53 family
Chromosomal Location of Human Ortholog: 22q12.1
Cellular Component: chromosome, telomeric region; Golgi apparatus; nucleoplasm; PML body
Molecular Function: ATP binding; identical protein binding; 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; DNA damage checkpoint; DNA damage induced protein phosphorylation; DNA damage response, signal transduction; DNA damage response, signal transduction resulting in induction of apoptosis; DNA repair; double-strand break repair; G2/M transition of mitotic cell cycle; peptidyl-serine phosphorylation; positive regulation of protein amino acid phosphorylation; positive regulation of transcription, DNA-dependent; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein stabilization; regulation of protein catabolic process; regulation of transcription, DNA-dependent; replicative cell aging; response to DNA damage stimulus; response to gamma radiation; transcription, DNA-dependent
Disease: Breast Cancer; Li-fraumeni Syndrome 2; Osteogenic Sarcoma; Prostate Cancer
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