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Showing Protein Serine/threonine-protein kinase Chk2 (HMDBP01248)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 3 metabolites
Identification
HMDB Protein ID HMDBP01248
Secondary Accession Numbers
  • 6544
Name Serine/threonine-protein kinase Chk2
Synonyms
  1. Cds1
Gene Name CHEK2
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific Function Regulates cell cycle checkpoints and 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' and 'Ser-20'
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Isoform 12:Nucleus
Gene Properties
Chromosome Location Chromosome:2
Locus 22q11|22q12.1
SNPs CHEK2
Gene Sequence 
>1632 bp
ATGTCTCGGGAGTCGGATGTTGAGGCTCAGCAGTCTCATGGCAGCAGTGCCTGTTCACAG
CCCCATGGCAGCGTTACCCAGTCCCAAGGCTCCTCCTCACAGTCCCAGGGCATATCCAGC
TCCTCTACCAGCACGATGCCAAACTCCAGCCAGTCCTCTCACTCCAGCTCTGGGACACTG
AGCTCCTTAGAGACAGTGTCCACTCAGGAACTCTATTCTATTCCTGAGGACCAAGAACCT
GAGGACCAAGAACCTGAGGAGCCTACCCCTGCCCCCTGGGCTCGATTATGGGCCCTTCAG
GATGGATTTGCCAATCTTGAATGTGTGAATGACAACTACTGGTTTGGGAGGGACAAAAGC
TGTGAATATTGCTTTGATGAACCACTGCTGAAAAGAACAGATAAATACCGAACATACAGC
AAGAAACACTTTCGGATTTTCAGGGAAGTGGGTCCTAAAAACTCTTACATTGCATACATA
GAAGATCACAGTGGCAATGGAACCTTTGTAAATACAGAGCTTGTAGGGAAAGGAAAACGC
CGTCCTTTGAATAACAATTCTGAAATTGCACTGTCACTAAGCAGAAATAAAGTTTTTGTC
TTTTTTGATCTGACTGTAGATGATCAGTCAGTTTATCCTAAGGCATTAAGAGATGAATAC
ATCATGTCAAAAACTCTTGGAAGTGGTGCCTGTGGAGAGGTAAAGCTGGCTTTCGAGAGG
AAAACATGTAAGAAAGTAGCCATAAAGATCATCAGCAAAAGGAAGTTTGCTATTGGTTCA
GCAAGAGAGGCAGACCCAGCTCTCAATGTTGAAACAGAAATAGAAATTTTGAAAAAGCTA
AATCATCCTTGCATCATCAAGATTAAAAACTTTTTTGATGCAGAAGATTATTATATTGTT
TTGGAATTGATGGAAGGGGGAGAGCTGTTTGACAAAGTGGTGGGGAATAAACGCCTGAAA
GAAGCTACCTGCAAGCTCTATTTTTACCAGATGCTCTTGGCTGTGCAGTACCTTCATGAA
AACGGTATTATACACCGTGACTTAAAGCCAGAGAATGTTTTACTGTCATCTCAAGAAGAG
GACTGTCTTATAAAGATTACTGATTTTGGGCACTCCAAGATTTTGGGAGAGACCTCTCTC
ATGAGAACCTTATGTGGAACCCCCACCTACTTGGCGCCTGAAGTTCTTGTTTCTGTTGGG
ACTGCTGGGTATAACCGTGCTGTGGACTGCTGGAGTTTAGGAGTTATTCTTTTTATCTGC
CTTAGTGGGTATCCACCTTTCTCTGAGCATAGGACTCAAGTGTCACTGAAGGATCAGATC
ACCAGTGGAAAATACAACTTCATTCCTGAAGTCTGGGCAGAAGTCTCAGAGAAAGCTCTG
GACCTTGTCAAGAAGTTGTTGGTAGTGGATCCAAAGGCACGTTTTACGACAGAAGAAGCC
TTAAGACACCCGTGGCTTCAGGATGAAGACATGAAGAGAAAGTTTCAAGATCTTCTGTCT
GAGGAAAATGAATCCACAGCTCTACCCCAGGTTCTAGCCCAGCCTTCTACTAGTCGAAAG
CGGCCCCGTGAAGGGGAAGCCGAGGGTGCCGAGACCACAAAGCGCCCAGCTGTGTGTGCT
GCTGTGTTGTGA
Protein Properties
Number of Residues 543
Molecular Weight 60914.3
Theoretical pI 5.72
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Serine/threonine-protein kinase Chk2
MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTL
SSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKS
CEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKR
RPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFER
KTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIV
LELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEE
DCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFIC
LSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEA
LRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCA
AVL
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O96017
UniProtKB/Swiss-Prot Entry Name CHK2_HUMAN
PDB IDs
GenBank Gene ID AF086904
GeneCard ID CHEK2
GenAtlas ID CHEK2
HGNC ID HGNC:16627
References
General References
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  5. Matsuoka S, Huang M, Elledge SJ: Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science. 1998 Dec 4;282(5395):1893-7. [PubMed:9836640 ]
  6. Blasina A, de Weyer IV, Laus MC, Luyten WH, Parker AE, McGowan CH: A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Curr Biol. 1999 Jan 14;9(1):1-10. [PubMed:9889122 ]
  7. Brown AL, Lee CH, Schwarz JK, Mitiku N, Piwnica-Worms H, Chung JH: 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. 1999 Mar 30;96(7):3745-50. [PubMed:10097108 ]
  8. Staalesen V, Falck J, Geisler S, Bartkova J, Borresen-Dale AL, Lukas J, Lillehaug JR, Bartek J, Lonning PE: Alternative splicing and mutation status of CHEK2 in stage III breast cancer. Oncogene. 2004 Nov 4;23(52):8535-44. [PubMed:15361853 ]
  9. Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R: The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway. J Biol Chem. 2004 Nov 12;279(46):47652-60. Epub 2004 Sep 1. [PubMed:15342622 ]
  10. Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW: Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009 Jan 15;8(2):327-9. [PubMed:19164942 ]
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  14. Lee SB, Kim SH, Bell DW, Wahrer DC, Schiripo TA, Jorczak MM, Sgroi DC, Garber JE, Li FP, Nichols KE, Varley JM, Godwin AK, Shannon KM, Harlow E, Haber DA: Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. Cancer Res. 2001 Nov 15;61(22):8062-7. [PubMed:11719428 ]
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  17. Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, Koeffler HP: Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Genes Chromosomes Cancer. 2002 Jan;33(1):17-21. [PubMed:11746983 ]
  18. Dong X, Wang L, Taniguchi K, Wang X, Cunningham JM, McDonnell SK, Qian C, Marks AF, Slager SL, Peterson BJ, Smith DI, Cheville JC, Blute ML, Jacobsen SJ, Schaid DJ, Tindall DJ, Thibodeau SN, Liu W: Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet. 2003 Feb;72(2):270-80. Epub 2003 Jan 17. [PubMed:12533788 ]
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  21. Cybulski C, Gorski B, Huzarski T, Masojc B, Mierzejewski M, Debniak T, Teodorczyk U, Byrski T, Gronwald J, Matyjasik J, Zlowocka E, Lenner M, Grabowska E, Nej K, Castaneda J, Medrek K, Szymanska A, Szymanska J, Kurzawski G, Suchy J, Oszurek O, Witek A, Narod SA, Lubinski J: CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet. 2004 Dec;75(6):1131-5. Epub 2004 Oct 18. [PubMed:15492928 ]
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  24. Dufault MR, Betz B, Wappenschmidt B, Hofmann W, Bandick K, Golla A, Pietschmann A, Nestle-Kramling C, Rhiem K, Huttner C, von Lindern C, Dall P, Kiechle M, Untch M, Jonat W, Meindl A, Scherneck S, Niederacher D, Schmutzler RK, Arnold N: Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer. 2004 Jun 20;110(3):320-5. [PubMed:15095295 ]
  25. Kilpivaara O, Vahteristo P, Falck J, Syrjakoski K, Eerola H, Easton D, Bartkova J, Lukas J, Heikkila P, Aittomaki K, Holli K, Blomqvist C, Kallioniemi OP, Bartek J, Nevanlinna H: CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer. 2004 Sep 10;111(4):543-7. [PubMed:15239132 ]
  26. Shaag A, Walsh T, Renbaum P, Kirchhoff T, Nafa K, Shiovitz S, Mandell JB, Welcsh P, Lee MK, Ellis N, Offit K, Levy-Lahad E, King MC: Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Hum Mol Genet. 2005 Feb 15;14(4):555-63. Epub 2005 Jan 13. [PubMed:15649950 ]
  27. Bogdanova N, Enssen-Dubrowinskaja N, Feshchenko S, Lazjuk GI, Rogov YI, Dammann O, Bremer M, Karstens JH, Sohn C, Dork T: Association of two mutations in the CHEK2 gene with breast cancer. Int J Cancer. 2005 Aug 20;116(2):263-6. [PubMed:15810020 ]
  28. van Puijenbroek M, van Asperen CJ, van Mil A, Devilee P, van Wezel T, Morreau H: Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype. J Pathol. 2005 Jun;206(2):198-204. [PubMed:15818573 ]