checkpoint kinase 2; serine/threonine protein kinase Chk2; homolog of S. cerevisiae Rad53; Cds1 (CHEK2, CHK2, RAD53)
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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
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
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:
Laboratory
Notes
some isoforms may be catalytically inactive
More general terms
References
- ↑ OMIM https://mirror.omim.org/entry/604373
- ↑ Matsuoka S et al Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893-7, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9836640
- ↑ Hirao A et al DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287:1824-7, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10710310
- ↑ Bell DW et al Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286:2528-31, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10617473
- ↑ UniProt http://www.uniprot.org/uniprot/O96017.html
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/CHEK2ID312.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CHEK2
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/chek2/
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=11200
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:11200
- OMIM: https://mirror.omim.org/entry/176807
- OMIM: https://mirror.omim.org/entry/259500
- OMIM: https://mirror.omim.org/entry/604373
- OMIM: https://mirror.omim.org/entry/609265
- UniProt: http://www.uniprot.org/uniprot/O96017.html