Catalytic activity:ATP + a protein = ADP + a phosphoprotein. ,cofactor:Magnesium. ,Disease:Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53. ,Disease:Defects in CHEK2 are found in some patients with osteosarcoma (OSRC) [MIM:259500]. ,Disease:Defects in CHEK2 are found in some patients with prostate cancer (CaP) [MIM:176807]. ,enzyme regulation:Rapidly phosphorylated on Thr-68 by MLTK in response to DNA damage and to replication block. Kinase activity is also up-regulated by autophosphorylation. ,Function:Regulates cell cycle checkpoints and apoptosis in response to DNA damage , particularly to DNA double-strand breaks. Inhibits CDC25C phosphatase by phosphorylation on 'Ser-216' , preventing the entry into mitosis. May also play a role in meiosis. Regulates the TP53 tumor suppressor through phosphorylation at 'Thr-18' and 'Ser-20'. ,similarity:Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily. ,similarity:Contains 1 FHA domain. ,similarity:Contains 1 protein kinase domain. ,subcellular location:Isoform 10 is present throughout the cell. ,tissue specificity:High expression is found in testis , spleen , colon and peripheral blood leukocytes. Low expression is found in other tissues. ,
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