Checkpoint Kinase 2 (CHEK2)

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RAD53; CDS1; CHK2; HuCds1; Serine/threonine-protein kinase Chk2

Checkpoint Kinase 2 (CHEK2)
The longest human cDNA encoded a 543-amino acid protein with 83% identity to mouse Chk2 and 34% identity to Drosophila Dmnk, a protein highly expressed in ovaries for which a function in meiosis had been suggested. Human CHK2 protein is 26% identical to Rad53 and 26% identical to cds1+. Sequence analysis revealed a single forkhead-associated (FHA) domain, a 60-amino acid protein interaction domain essential for activation in response to DNA damage that is conserved in the Rad53/cds1+ family of kinases. CHK2 has a potential regulatory region rich in SQ and TQ amino acid pairs. Northern blot analysis revealed wide expression of small amounts of CHK2 mRNA with larger amounts in human testis, spleen, colon, and peripheral blood leukocytes. CHK2 complemented the lethality of a Rad53 deletion.

Organism species: Homo sapiens (Human)

CATALOG NO. PRODUCT NAME APPLICATIONS
Proteins RPP087Hu01 Recombinant Checkpoint Kinase 2 (CHEK2) Positive Control; Immunogen; SDS-PAGE; WB.
Antibodies PAP087Hu01 Polyclonal Antibody to Checkpoint Kinase 2 (CHEK2) WB; IHC; ICC; IP.
Assay Kits n/a CLIA Kit for Checkpoint Kinase 2 (CHEK2) CLIA Kit Customized Service Offer
n/a ELISA Kit for Checkpoint Kinase 2 (CHEK2) ELISA Kit Customized Service Offer

Organism species: Mus musculus (Mouse)

CATALOG NO. PRODUCT NAME APPLICATIONS
Proteins n/a Recombinant Checkpoint Kinase 2 (CHEK2) Recombinant Protein Customized Service Offer
Antibodies n/a Monoclonal Antibody to Checkpoint Kinase 2 (CHEK2) Monoclonal Antibody Customized Service Offer
n/a Polyclonal Antibody to Checkpoint Kinase 2 (CHEK2) Polyclonal Antibody Customized Service Offer
Assay Kits n/a CLIA Kit for Checkpoint Kinase 2 (CHEK2) CLIA Kit Customized Service Offer
n/a ELISA Kit for Checkpoint Kinase 2 (CHEK2) ELISA Kit Customized Service Offer

Organism species: Rattus norvegicus (Rat)

CATALOG NO. PRODUCT NAME APPLICATIONS
Proteins n/a Recombinant Checkpoint Kinase 2 (CHEK2) Recombinant Protein Customized Service Offer
Antibodies n/a Monoclonal Antibody to Checkpoint Kinase 2 (CHEK2) Monoclonal Antibody Customized Service Offer
n/a Polyclonal Antibody to Checkpoint Kinase 2 (CHEK2) Polyclonal Antibody Customized Service Offer
Assay Kits n/a CLIA Kit for Checkpoint Kinase 2 (CHEK2) CLIA Kit Customized Service Offer
n/a ELISA Kit for Checkpoint Kinase 2 (CHEK2) ELISA Kit Customized Service Offer
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  2. "A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase."Curr. Biol. 9:1-10(1999) [PubMed] [Europe PMC] [Abstract]
  3. "A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage."Proc. Natl. Acad. Sci. U.S.A. 96:3745-3750(1999) [PubMed] [Europe PMC] [Abstract]
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  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
  10. "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response."Nature 404:201-204(2000) [PubMed] [Europe PMC] [Abstract]
  11. "Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro."Proc. Natl. Acad. Sci. U.S.A. 97:10389-10394(2000) [PubMed] [Europe PMC] [Abstract]
  12. "The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation."J. Biol. Chem. 276:30537-30541(2001) [PubMed] [Europe PMC] [Abstract]
  13. "The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis."Nature 410:842-847(2001) [PubMed] [Europe PMC] [Abstract]
  14. "A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer."Am. J. Hum. Genet. 71:432-438(2002) [PubMed] [Europe PMC] [Abstract]
  15. "Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain."J. Biol. Chem. 277:19389-19395(2002) [PubMed] [Europe PMC] [Abstract]
  16. "PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2."Nat. Cell Biol. 4:865-870(2002) [PubMed] [Europe PMC] [Abstract]
  17. "53BP1, a mediator of the DNA damage checkpoint."Science 298:1435-1438(2002) [PubMed] [Europe PMC] [Abstract]
  18. "The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation."J. Biol. Chem. 278:33134-33141(2003) [PubMed] [Europe PMC] [Abstract]
  19. "Chk2 activates E2F-1 in response to DNA damage."Nat. Cell Biol. 5:401-409(2003) [PubMed] [Europe PMC] [Abstract]
  20. "MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways."Nature 421:957-961(2003) [PubMed] [Europe PMC] [Abstract]
  21. "The Chk2 protein kinase."DNA Repair 3:1039-1047(2004) [PubMed] [Europe PMC] [Abstract]
  22. "The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway."J. Biol. Chem. 279:47652-47660(2004) [PubMed] [Europe PMC] [Abstract]
  23. "ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage."EMBO J. 24:3411-3422(2005) [PubMed] [Europe PMC] [Abstract]
  24. "Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase."Cell Death Differ. 13:1170-1180(2006) [PubMed] [Europe PMC] [Abstract]
  25. "Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its full activation by ATM and a downstream checkpoint in response to DNA damage."Mutat. Res. 596:166-176(2006) [PubMed] [Europe PMC] [Abstract]
  26. "Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage."EMBO J. 26:2083-2093(2007) [PubMed] [Europe PMC] [Abstract]
  27. "Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456."J. Biol. Chem. 282:30311-30321(2007) [PubMed] [Europe PMC] [Abstract]
  28. "Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes."Mol. Cell. Biol. 27:1007-1016(2007) [PubMed] [Europe PMC] [Abstract]
  29. "Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation."Cell Cycle 7:2705-2709(2008) [PubMed] [Europe PMC] [Abstract]
  30. "Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379."Mol. Cell. Biol. 28:5874-5885(2008) [PubMed] [Europe PMC] [Abstract]
  31. "The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage."Oncogene 27:3977-3985(2008) [PubMed] [Europe PMC] [Abstract]
  32. "Polo-like kinase 4 phosphorylates Chk2."Cell Cycle 8:327-329(2009) [PubMed] [Europe PMC] [Abstract]
  33. "The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells."Nat. Cell Biol. 12:492-499(2010) [PubMed] [Europe PMC] [Abstract]
  34. "Initial characterization of the human central proteome."BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
  35. "A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women."Hum. Mutat. 32:1000-1003(2011) [PubMed] [Europe PMC] [Abstract]
  36. "The E3 ligase RNF8 regulates KU80 removal and NHEJ repair."Nat. Struct. Mol. Biol. 19:201-206(2012) [PubMed] [Europe PMC] [Abstract]
  37. "Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2."Mol. Cell 9:1045-1054(2002) [PubMed] [Europe PMC] [Abstract]
  38. "Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange."EMBO J. 25:3179-3190(2006) [PubMed] [Europe PMC] [Abstract]
  39. "Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase."Mol. Cell 35:818-829(2009) [PubMed] [Europe PMC] [Abstract]
  40. "Collaborator of ARF (CARF) regulates proliferative fate of human cells by dose-dependent regulation of DNA damage signaling."J. Biol. Chem. 289:18258-18269(2014) [PubMed] [Europe PMC] [Abstract]
  41. "Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome."Science 286:2528-2531(1999) [PubMed] [Europe PMC] [Abstract]
  42. "Mutation analysis of the CHK2 gene in families with hereditary breast cancer."Br. J. Cancer 85:209-212(2001) [PubMed] [Europe PMC] [Abstract]
  43. "Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome."Cancer Res. 61:8062-8067(2001) [PubMed] [Europe PMC] [Abstract]
  44. "Mutation analysis of the CHK2 gene in breast carcinoma and other cancers."Breast Cancer Res. 4:R4-R4(2002) [PubMed] [Europe PMC] [Abstract]
  45. "CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours."Br. J. Cancer 87:1445-1448(2002) [PubMed] [Europe PMC] [Abstract]
  46. "Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors."Genes Chromosomes Cancer 33:17-21(2002) [PubMed] [Europe PMC] [Abstract]
  47. "Mutations in CHEK2 associated with prostate cancer risk."Am. J. Hum. Genet. 72:270-280(2003) [PubMed] [Europe PMC] [Abstract]
  48. "Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility." Am. J. Hum. Genet. 72:1023-1028(2003) [PubMed] [Europe PMC] [Abstract]
  49. "CHEK2 variants associate with hereditary prostate cancer."Br. J. Cancer 89:1966-1970(2003) [PubMed] [Europe PMC] [Abstract]
  50. "CHEK2 is a multiorgan cancer susceptibility gene." Am. J. Hum. Genet. 75:1131-1135(2004) [PubMed] [Europe PMC] [Abstract]
  51. "Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women."Breast Cancer Res. 6:R629-R635(2004) [PubMed] [Europe PMC] [Abstract]
  52. "A novel founder CHEK2 mutation is associated with increased prostate cancer risk."Cancer Res. 64:2677-2679(2004) [PubMed] [Europe PMC] [Abstract]
  53. "Limited relevance of the CHEK2 gene in hereditary breast cancer."Int. J. Cancer 110:320-325(2004) [PubMed] [Europe PMC] [Abstract]
  54. "CHEK2 variant I157T may be associated with increased breast cancer risk."Int. J. Cancer 111:543-547(2004) [PubMed] [Europe PMC] [Abstract]
  55. "Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population."Hum. Mol. Genet. 14:555-563(2005) [PubMed] [Europe PMC] [Abstract]
  56. "Association of two mutations in the CHEK2 gene with breast cancer."Int. J. Cancer 116:263-266(2005) [PubMed] [Europe PMC] [Abstract]
  57. "Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype."J. Pathol. 206:198-204(2005) [PubMed] [Europe PMC] [Abstract]
  58. "A novel recurrent CHEK2 Y390C mutation identified in high-risk Chinese breast cancer patients impairs its activity and is associated with increased breast cancer risk."Oncogene 0:0-0(2015) [PubMed] [Europe PMC] [Abstract]