Description
Product Characteristics:
Chk2 is a serine/threonine kinase involved in the control of cell cycle checkpoints, and may also participate in transduction of the DNA damage and replicational stress signals. Chk2 is the mammalian ortholog of the budding yeast Rad53 and fission yeast Cds1 checkpoint kinases. The amino-terminal domain of Chk2 contains a series of seven serine and threonine residues (Ser19, Thr26, Ser28, Ser33, Ser35, Ser50 and Thr68) followed by glutamine (SQ or TQ motif). These are known to be preferred sites for phosphorylation by ATM/ATR kinases. Indeed, after DNA damage by ionizing radiation (IR), UV irradiation or hydroxyurea treatment, Thr68 and other sites in this region become phosphorylated by ATM/ATR. The SQ/TQ cluster domain, therefore, seems to have a regulatory function. Phosphorylation at Thr68 is a prerequisite for the subsequent activation step, which is attributable to autophosphorylation of Chk2 on residues Thr383 and Thr387 in the activation loop of the kinase domain. Chk2 inhibits CDC25C phosphatase by phosphorylating it on Ser-216, preventing the entry into mitosis. This kinase may have a role in meiosis as well. Kinase activity is up regulated by autophosphorylation and the protein is rapidly phosphorylated in response to DNA damage and to replication block.
Synonyms: Chk2 Ser516, bA444G7, CHK2 checkpoint homolog, CHK2_HUMAN, Serine/threonine-protein kinase Chk2, CDS 1, CDS1, Checkpoint kinase 2, Checkpoint like protein CHK2, Chek 2, Chek2, Chk 2, CHK2 checkpoint homolog S. pombe, CHK2 checkpoint homolog, HuCds 1, HuCds1, LFS 2, LFS2, PP1425, RAD 53, RAD53, Rad53 homolog, Serine/threonine protein kinase Chk2.
Target Information: 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]