Chk2, GST-His Tag (CHEK2) Human Active Protein

In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is 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. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

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: EC 2.7.11.1; Protein kinase, CAMK; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Tumor suppressor; CAMK group; RAD53 family

Chromosomal Location of Human Ortholog: 22q12.1

Cellular Component: nucleoplasm; Golgi apparatus; PML body; chromosome, telomeric region

Molecular Function: protein serine/threonine kinase activity; identical protein binding; protein binding; protein homodimerization activity; ubiquitin protein ligase binding; metal ion binding; protein kinase binding; ATP binding

Biological Process: transcription, DNA-dependent; protein stabilization; DNA damage induced protein phosphorylation; protein amino acid autophosphorylation; positive regulation of transcription, DNA-dependent; DNA damage response, signal transduction; protein amino acid phosphorylation; DNA damage response, signal transduction resulting in induction of apoptosis; regulation of transcription, DNA-dependent; cell division; cellular protein catabolic process; double-strand break repair; DNA damage checkpoint; response to gamma radiation; regulation of protein catabolic process; G2/M transition of mitotic cell cycle; response to DNA damage stimulus

Disease: Li-fraumeni Syndrome 2; Prostate Cancer; Breast Cancer; Osteogenic Sarcoma