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checkpoint kinase 2; serine/threonine protein kinase Chk2; homolog of S. cerevisiae Rad53; Cds1 (CHEK2, CHK2, RAD53)

Function: - regulates cell cycle checkpoints & 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 & Ser-20 - phosphorylates BRCA1 on Ser-988 - rapidly phosphorylated on Thr-68 by MLTK in response to DNA damage & to replication block (ATM-dependent) - kinase activity is also up-regulated by autophosphorylation Cofactor: Mg+2 Structure: - belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, CHK2 subfamily - contains 1 FHA domain - contains 1 protein kinase domain Compartment: - isoforms 2,4,7,9,12: nucleus - isoform 10 is present throughout cell Alternative splicing: named isoforms=12 Expression: - high expression is found in testis, spleen, colon & peripheral blood leukocytes - low expression is found in other tissues Pathology: - defects in CHEK2 are associated with Li-Fraumeni syndrome 2 - defects in CHEK2 are found in some patients with: a) prostate cancer b) osteosarcoma Laboratory: - CHEK2 gene mutation Notes: some isoforms may be catalytically inactive

Interactions

molecular events

General

checkpoint kinase

Properties

SIZE: entity length = 543 aa MW = 61 kD COMPARTMENT: cell nucleus STATE: active state MOTIF: Thr phosphorylation site {T68} forkhead-associated (FHA) domain {113-175} kinase domain SITE: 220-486 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 226-234 ATP-binding site NAME: ATP-binding site SITE: 249-249 aspartate residue {D347}

References

  1. OMIM :accession 604373
  2. Matsuoka S et al Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893-7, 1998 PMID: 9836640
  3. Hirao A et al DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287:1824-7, 2000 PMID: 10710310
  4. Bell DW et al Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286:2528-31, 1999 PMID: 10617473
  5. UniProt :accession O96017
  6. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/CHEK2ID312.html
  7. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CHEK2
  8. NIEHS-SNPs http://egp.gs.washington.edu/data/chek2/

Databases & Figures

OMIM correlations MORBIDMAP 604373 UniProt O96017 PFAM correlations Entrez Gene 11200 Kegg hsa:11200 ENZYME 2.7.11.1 Figures/diagrams/slides/tables related to checkpoint kinase 2 (CHK2)