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CHEK2 (CHK2)

Protein FULL name:

serine/threonine-protein kinase Chk2 isoform a [Homo sapiens].


Protein SHORT name:

CHK2, RAD53


CHEK2 (CHK2) (Homo sapiens) is product of expression of CHEK2 gene.

Human diseases related to this protein:

CHEK2 (CHK2) is involved in:

DDS in Homo sapiens
     


Keywords:



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'.

CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.

COFACTOR: Magnesium.

ENZYME REGULATION: Rapidly phosphorylated on Thr-68 by MLTK in response to DNA damage and to replication block. Kinase activity is also up-regulated by autophosphorylation.

INTERACTION: Q9NY61:AATF; NbExp=3; IntAct=EBI-1180783, EBI-372428; Q9Y248:GINS2; NbExp=1; IntAct=EBI-1180783, EBI-747491; P53350:PLK1; NbExp=3; IntAct=EBI-1180783, EBI-476768; Q15172:PPP2R5A; NbExp=1; IntAct=EBI-1180783, EBI-641666; Q15173:PPP2R5B; NbExp=1; IntAct=EBI-1180783, EBI-1369497; Q13362-1:PPP2R5C; NbExp=3; IntAct=EBI-1180783, EBI-1266170; Q13362-2:PPP2R5C; NbExp=1; IntAct=EBI-1180783, EBI-1266173; Q13362-3:PPP2R5C; NbExp=3; IntAct=EBI-1180783, EBI-1266176; Q16537:PPP2R5E; NbExp=3; IntAct=EBI-1180783, EBI-968374; P02340:Tp53 (xeno); NbExp=1; IntAct=EBI-1180783, EBI-474016; P55072:VCP; NbExp=2; IntAct=EBI-1180783, EBI-355164;

SUBCELLULAR LOCATION: Isoform 2: Nucleus. Note=Isoform 10 is present throughout the cell.

SUBCELLULAR LOCATION: Isoform 4: Nucleus.

SUBCELLULAR LOCATION: Isoform 7: Nucleus.

SUBCELLULAR LOCATION: Isoform 9: Nucleus.

SUBCELLULAR LOCATION: Isoform 12: Nucleus.

TISSUE SPECIFICITY: High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.

PTM: Phosphorylated by PLK4.

DISEASE: Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.

DISEASE: Defects in CHEK2 are found in some patients with prostate cancer (CaP) [MIM:176807].

DISEASE: Defects in CHEK2 are found in some patients with osteosarcoma (OSRC) [MIM:259500].

SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily.

SIMILARITY: Contains 1 FHA domain.

SIMILARITY: Contains 1 protein kinase domain.

WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]

WEB RESOURCE: Name=GeneReviews; [LINK]

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 6005850
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot O96017 O96017
PFAM: - O96017 (Link - using uniprot id)
InterPro: - O96017 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSS
QSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQ
DGFANLECVNDNYWFGRDKSCEYCFDEPLLKRTDKYRTYSKKHFRIFREV
GPKNSYIAYIEDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFV
FFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKI
ISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIV
LELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKP
ENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVG
TAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPE
VWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLS
EENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL

CHEK2 (CHK2) (Homo sapiens) is able to recognize following damages:
CHEK2 (CHK2) (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Matsuoka S, Huang M, Elledge SJ Science Dec. 4, 1998
A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Blasina A, de Weyer IV, Laus MC, Luyten WH, Parker AE, McGowan CH Curr Biol Feb. 14, 1999
A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. Brown AL, Lee CH, Schwarz JK, Mitiku N, Piwnica-Worms H, Chung JH Proc Natl Acad Sci U S A March 1, 1999
The DNA sequence of human chromosome 22. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al. Nature Dec. 2, 1999
Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA Science Dec. 24, 1999
Mutation analysis of the CHK2 gene in families with hereditary breast cancer. Allinen M, Huusko P, Mantyniemi S, Launonen V, Winqvist R Br J Cancer July 20, 2001
Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. 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 Cancer Res Nov. 15, 2001
Mutation analysis of the CHK2 gene in breast carcinoma and other cancers. Ingvarsson S, Sigbjornsdottir BI, Huiping C, Hafsteinsdottir SH, Ragnarsson G, Barkardottir RB, Arason A, Egilsson V, Bergthorsson JT Breast Cancer Res Jan. 1, 2002
Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, Koeffler HP Genes Chromosomes Cancer Feb. 1, 2002
Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2. Li J, Williams BL, Haire LF, Goldberg M, Wilker E, Durocher D, Yaffe MB, Jackson SP, Smerdon SJ Mol Cell May 1, 2002
CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours. Sodha N, Bullock S, Taylor R, Mitchell G, Guertl-Lackner B, Williams RD, Bevan S, Bishop K, McGuire S, Houlston RS, Eeles RA Br J Cancer Dec. 2, 2002
Mutations in CHEK2 associated with prostate cancer risk. 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 Am J Hum Genet Jan. 1, 2003
Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG, Eccles D, Meijers C, Lohman F, Klijn J, van den Ouweland A, Futreal PA, Nathanson KL, Weber BL, Easton DF, Stratton MR, Rahman N Am J Hum Genet April 1, 2003
CHEK2 variants associate with hereditary prostate cancer. Seppala EH, Ikonen T, Mononen N, Autio V, Rokman A, Matikainen MP, Tammela TL, Schleutker J Br J Cancer Nov. 17, 2003
A genome annotation-driven approach to cloning the human ORFeome. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I Genome Biol Jan. 1, 2004
Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women. Friedrichsen DM, Malone KE, Doody DR, Daling JR, Ostrander EA Breast Cancer Res Jan. 1, 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S Nat Genet Feb. 1, 2004
A novel founder CHEK2 mutation is associated with increased prostate cancer risk. Cybulski C, Huzarski T, Gorski B, Masojc B, Mierzejewski M, Debniak T, Gliniewicz B, Matyjasik J, Zlowocka E, Kurzawski G, Sikorski A, Posmyk M, Szwiec M, Czajka R, Narod SA, Lubinski J Cancer Res April 15, 2004
Limited relevance of the CHEK2 gene in hereditary breast cancer. 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 Int J Cancer June 20, 2004
CHEK2 variant I157T may be associated with increased breast cancer risk. 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 Int J Cancer Sept. 10, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Alternative splicing and mutation status of CHEK2 in stage III breast cancer. Staalesen V, Falck J, Geisler S, Bartkova J, Borresen-Dale AL, Lukas J, Lillehaug JR, Bartek J, Lonning PE Oncogene Nov. 4, 2004
The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway. Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R J Biol Chem Nov. 12, 2004
CHEK2 is a multiorgan cancer susceptibility gene. 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 Am J Hum Genet Dec. 1, 2004
Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. 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 Hum Mol Genet Jan. 15, 2005
Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype. van Puijenbroek M, van Asperen CJ, van Mil A, Devilee P, van Wezel T, Morreau H J Pathol June 1, 2005
Association of two mutations in the CHEK2 gene with breast cancer. Bogdanova N, Enssen-Dubrowinskaja N, Feshchenko S, Lazjuk GI, Rogov YI, Dammann O, Bremer M, Karstens JH, Sohn C, Dork T Int J Cancer Aug. 20, 2005
Polo-like kinase 4 phosphorylates Chk2. Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW Cell Cycle Feb. 15, 2009


Last modification of this entry: June 19, 2013.

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