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Gene Review

DGUOK  -  deoxyguanosine kinase

Homo sapiens

Synonyms: DGK, Deoxyguanosine kinase, mitochondrial, MTDPS3, dGK
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Disease relevance of DGUOK


High impact information on DGUOK


Chemical compound and disease context of DGUOK


Biological context of DGUOK

  • In striking contrast to ATP, the phosphorylation reaction follows strict Michaelis-Menten kinetics, with K(m) values of 74 and 92 microM for dCK and dGK, respectively, and V(max) values 40-50% that for ATP [12].
  • In conclusion, we observed a high prevalence of DGUOK mutations (17%) in patients with hepatic involvement and combined respiratory chain deficiencies with hepatic involvement [13].
  • We evaluated the hypothesis that dFdC-mediated deoxyribonucleoside triphosphate perturbation enhances the phosphorylation of substrates that use deoxycytidine kinase or deoxyguanosine kinase, because these enzymes are inhibited by dCTP or dGTP, respectively [14].
  • These mutations were associated with variable phenotypes, and their low frequencies suggests that dGK is not the only gene responsible for mitochondrial DNA depletion in liver [15].
  • Here we describe the subcellular distribution of dGK during apoptosis in human epithelial kidney 293 cells and human lymphoblast Molt-4 cells [16].

Anatomical context of DGUOK

  • However, low expression of dGK is the most apparent alteration in both resistant cell lines [17].
  • Two of the four human deoxyribonucleoside kinases, deoxyguanosine kinase (dGK) and thymidine kinase-2 (TK2), are expressed in mitochondria [18].
  • These results from whole-cell experiments are consistent with those from the cell-free system and strongly suggest that ara-G is phosphorylated by both kinases, and at low substrate concentrations, dGK is preferred enzyme [19].
  • The redistribution of dGK from the mitochondria to the cytosol may be of importance for the activation of apoptotic purine nucleoside cofactors such as dATP and demonstrates that mitochondrial matrix proteins may selectively leak out during apoptosis [16].
  • For this purpose, dCK and dGK analyses were done in blood cells from 59 untreated symptomatic patients with CLL [4].

Associations of DGUOK with chemical compounds


Other interactions of DGUOK

  • The analogue 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril (EN2) showed poor relative-phosphorylation efficiencies (kcat/Km) with both TK1 and dGK, but not with TK2 [22].
  • We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria [23].
  • Each affected child was homozygous for the novel DGUOK p.D255Y mutation, but had no CTH mutation, indicating that the hepatocerebral form of MDS might be associated with secondary cystathioninuria [24].
  • One mutant that lacked deoxycytidine kinase activity, designated CEM/ara-C, retained about 10% of wild-type deoxyadenosine kinase and deoxyguanosine kinase activity each but maintained normal adenosine kinase or thymidine kinase activity [25].
  • The mRNA expression for dCK, dGK and 5'-NT (expressed as the ratio of the respective gene and the reference gene) in pediatric ALL and AML patients showed a large interindividual variability from 0.06 to 2.34, non-detectable to 0.06 and 0.04 to 0.30, respectively [26].

Analytical, diagnostic and therapeutic context of DGUOK


  1. Cloning and expression of human deoxyguanosine kinase cDNA. Johansson, M., Karlsson, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes. Wang, L., Limongelli, A., Vila, M.R., Carrara, F., Zeviani, M., Eriksson, S. Mol. Genet. Metab. (2005) [Pubmed]
  3. Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene. Ma, N., Ikeda, S., Guo, S., Fieno, A., Park, I., Grimme, S., Ikeda, T., Ives, D.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia. Lotfi, K., Karlsson, K., Fyrberg, A., Juliusson, G., Jonsson, V., Peterson, C., Eriksson, S., Albertioni, F. Biochem. Pharmacol. (2006) [Pubmed]
  5. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. Nat. Genet. (2001) [Pubmed]
  6. Deoxyribonucleoside kinases: two enzyme families catalyze the same reaction. Sandrini, M.P., Piskur, J. Trends Biochem. Sci. (2005) [Pubmed]
  7. Structural basis for substrate specificities of cellular deoxyribonucleoside kinases. Johansson, K., Ramaswamy, S., Ljungcrantz, C., Knecht, W., Piskur, J., Munch-Petersen, B., Eriksson, S., Eklund, H. Nat. Struct. Biol. (2001) [Pubmed]
  8. Human deoxycytidine kinase is located in the cell nucleus. Johansson, M., Brismar, S., Karlsson, A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Cloning and expression of human mitochondrial deoxyguanosine kinase cDNA. Wang, L., Hellman, U., Eriksson, S. FEBS Lett. (1996) [Pubmed]
  10. New mutations in TK2 gene associated with mitochondrial DNA depletion. Galbiati, S., Bordoni, A., Papadimitriou, D., Toscano, A., Rodolico, C., Katsarou, E., Sciacco, M., Garufi, A., Prelle, A., Aguennouz, M., Bonsignore, M., Crimi, M., Martinuzzi, A., Bresolin, N., Papadimitriou, A., Comi, G.P. Pediatric neurology. (2006) [Pubmed]
  11. Antiviral guanosine analogs as substrates for deoxyguanosine kinase: implications for chemotherapy. Herrström Sjöberg, A., Wang, L., Eriksson, S. Antimicrob. Agents Chemother. (2001) [Pubmed]
  12. Inorganic tripolyphosphate (PPP(i)) as a phosphate donor for human deoxyribonucleoside kinases. Krawiec, K., Kierdaszuk, B., Shugar, D. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  13. Deoxyguanosine kinase mutations and combined deficiencies of the mitochondrial respiratory chain in patients with hepatic involvement. Slama, A., Giurgea, I., Debrey, D., Bridoux, D., de Lonlay, P., Levy, P., Chretien, D., Brivet, M., Legrand, A., Rustin, P., Munnich, A., Rötig, A. Mol. Genet. Metab. (2005) [Pubmed]
  14. Modulatory activity of 2',2'-difluorodeoxycytidine on the phosphorylation and cytotoxicity of arabinosyl nucleosides. Gandhi, V., Plunkett, W. Cancer Res. (1990) [Pubmed]
  15. Mitochondrial DNA depletion and dGK gene mutations. Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camaño, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C.M., Feigenbaum, A., Naini, A.B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T.H. Ann. Neurol. (2002) [Pubmed]
  16. Apoptosis induces efflux of the mitochondrial matrix enzyme deoxyguanosine kinase. Jüllig, M., Eriksson, S. J. Biol. Chem. (2001) [Pubmed]
  17. Low level of mitochondrial deoxyguanosine kinase is the dominant factor in acquired resistance to 9-beta-D-arabinofuranosylguanine cytotoxicity. Lotfi, K., Månsson, E., Peterson, C., Eriksson, S., Albertioni, F. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Saada, A., Shaag, A., Mandel, H., Nevo, Y., Eriksson, S., Elpeleg, O. Nat. Genet. (2001) [Pubmed]
  19. Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. Rodriguez, C.O., Mitchell, B.S., Ayres, M., Eriksson, S., Gandhi, V. Cancer Res. (2002) [Pubmed]
  20. Life on the salvage path: the deoxynucleoside kinase of Lactobacillus acidophilus R-26. Ives, D.H., Ikeda, S. Prog. Nucleic Acid Res. Mol. Biol. (1998) [Pubmed]
  21. Role of salvage and phosphorylation in the immunostimulatory activity of C8-substituted guanine ribonucleosides. Goodman, M.G. J. Immunol. (1988) [Pubmed]
  22. Phosphorylation of isocarbostyril- and difluorophenyl-nucleoside thymidine mimics by the human deoxynucleoside kinases. Al-Madhoun, A.S., Eriksson, S., Wang, Z.X., Naimi, E., Knaus, E.E., Wiebe, L.I. Nucleosides Nucleotides Nucleic Acids (2004) [Pubmed]
  23. Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: implications in apoptosis. Keszler, G., Spasokoukotskaja, T., Csapo, Z., Virga, S., Staub, M., Sasvari-Szekely, M. Nucleosides Nucleotides Nucleic Acids (2004) [Pubmed]
  24. Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria. Tadiboyina, V.T., Rupar, A., Atkison, P., Feigenbaum, A., Kronick, J., Wang, J., Hegele, R.A. Am. J. Med. Genet. A (2005) [Pubmed]
  25. Identification of the mechanism of activation of 9-beta-D-arabinofuranosyladenine in human lymphoid cells using mutants deficient in nucleoside kinases. Verhoef, V., Sarup, J., Fridland, A. Cancer Res. (1981) [Pubmed]
  26. Real-time quantitative PCR assays for deoxycytidine kinase, deoxyguanosine kinase and 5'-nucleotidase mRNA measurement in cell lines and in patients with leukemia. Månsson, E., Liliemark, E., Söderhäll, S., Gustafsson, G., Eriksson, S., Albertioni, F. Leukemia (2002) [Pubmed]
  27. Deoxynucleoside anabolic enzyme levels in acute myelocytic leukemia and chronic lymphocytic leukemia cells. Jacobsson, B., Albertioni, F., Eriksson, S. Cancer Lett. (2001) [Pubmed]
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