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Gene Review

TK2  -  thymidine kinase 2, mitochondrial

Homo sapiens

Synonyms: MTDPS2, MTTK, Mt-TK, SCA31, Thymidine kinase 2, mitochondrial
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Disease relevance of TK2


High impact information on TK2


Chemical compound and disease context of TK2


Biological context of TK2

  • Patient A was a compound heterozygote carrying the previously reported T77M mutation and a novel mutation (R161K) in the TK2 gene [10].
  • We identified a sequence-tagged site designed from the 3' region of the TK2 cDNA [4].
  • The consequences of the two point mutations of TK2 and the role of TK2 in mt disorders are discussed [11].
  • The pathogenicity of these mutations was confirmed by reduced TK2 activity in muscle (28% to 37% of controls) [12].
  • This report extends the phenotypic expression of primary TK2 deficiency and suggests that factors other than TK2 may modify expression of the clinical phenotype in patients with MDS syndrome [13].

Anatomical context of TK2


Associations of TK2 with chemical compounds

  • Sequencing of the TK2 gene showed a homozygous C-->T transition at nucleotide 228 in exon 5, which changes a threonine to a methionine at position 77 (T77M) [2].
  • The H121N mutant enzyme had normal K(m) values for thymidine (dThd) and deoxycytidine (dCyd), 6 and 11 microm, respectively, but 2- and 3-fold lower V(max) values as compared with wild type TK2 and markedly increased K(m) values for ATP, leading to decreased enzyme efficiency [11].
  • Thymidine kinase 2 (TK2) is a mitochondrial (mt) pyrimidine deoxynucleoside salvage enzyme involved in mtDNA precursor synthesis [11].
  • The recombinant TK2 was shown to phosphorylate the anti-cancer nucleoside analog 2',2'-difluorodeoxycytidine [4].
  • Cleavage of labeled TK2 with cyanogen bromide showed that dTTP was incorporated into a single 3-kDa peptide [14].

Regulatory relationships of TK2


Other interactions of TK2


Analytical, diagnostic and therapeutic context of TK2


  1. 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]
  2. Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene. Mancuso, M., Filosto, M., Bonilla, E., Hirano, M., Shanske, S., Vu, T.H., DiMauro, S. Arch. Neurol. (2003) [Pubmed]
  3. Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene. Oskoui, M., Davidzon, G., Pascual, J., Erazo, R., Gurgel-Giannetti, J., Krishna, S., Bonilla, E., De Vivo, D.C., Shanske, S., DiMauro, S. Arch. Neurol. (2006) [Pubmed]
  4. Cloning of the cDNA and chromosome localization of the gene for human thymidine kinase 2. Johansson, M., Karlsson, A. J. Biol. Chem. (1997) [Pubmed]
  5. Thymidine kinase isoenzymes in human malignant lymphoma. Ellims, P.H., Van der Weyden, M.B., Medley, G. Cancer Res. (1981) [Pubmed]
  6. 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]
  7. Can thymidine kinase levels in breast tumors predict disease recurrence? O'Neill, K.L., Hoper, M., Odling-Smee, G.W. J. Natl. Cancer Inst. (1992) [Pubmed]
  8. Mitochondrial myopathies. Dimauro, S. Current opinion in rheumatology. (2006) [Pubmed]
  9. Tight binding of deoxyribonucleotide triphosphates to human thymidine kinase 2 expressed in Escherichia coli. Purification and partial characterization of its dimeric and tetrameric forms. Barroso, J.F., Elholm, M., Flatmark, T. Biochemistry (2003) [Pubmed]
  10. 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]
  11. Kinetic properties of mutant human thymidine kinase 2 suggest a mechanism for mitochondrial DNA depletion myopathy. Wang, L., Saada, A., Eriksson, S. J. Biol. Chem. (2003) [Pubmed]
  12. Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. Mancuso, M., Salviati, L., Sacconi, S., Otaegui, D., Camaño, P., Marina, A., Bacman, S., Moraes, C.T., Carlo, J.R., Garcia, M., Garcia-Alvarez, M., Monzon, L., Naini, A.B., Hirano, M., Bonilla, E., Taratuto, A.L., DiMauro, S., Vu, T.H. Neurology (2002) [Pubmed]
  13. Reversion of mtDNA depletion in a patient with TK2 deficiency. Vilà, M.R., Segovia-Silvestre, T., Gámez, J., Marina, A., Naini, A.B., Meseguer, A., Lombès, A., Bonilla, E., DiMauro, S., Hirano, M., Andreu, A.L. Neurology (2003) [Pubmed]
  14. Mammalian thymidine kinase 2. Direct photoaffinity labeling with [32P]dTTP of the enzyme from spleen, liver, heart and brain. Jansson, O., Bohman, C., Munch-Petersen, B., Eriksson, S. Eur. J. Biochem. (1992) [Pubmed]
  15. Novel selective human mitochondrial kinase inhibitors: Design, synthesis and enzymatic activity. Ciliberti, N., Manfredini, S., Angusti, A., Durini, E., Solaroli, N., Vertuani, S., Buzzoni, L., Bonache, M.C., Ben-Shalom, E., Karlsson, A., Saada, A., Balzarini, J. Bioorg. Med. Chem. (2007) [Pubmed]
  16. Thymidine and 3'-azido-3'-deoxythymidine metabolism in human peripheral blood lymphocytes and monocyte-derived macrophages. A study of both anabolic and catabolic pathways. Arnér, E.S., Valentin, A., Eriksson, S. J. Biol. Chem. (1992) [Pubmed]
  17. Prognostic relevance of thymidine kinase isozymes in adult non-Hodgkin's lymphoma. Ellims, P.H., Eng Gan, T., Medley, G., Van Der Weyden, M.B. Blood (1981) [Pubmed]
  18. Human thymidine kinase 1. Regulation in normal and malignant cells. Munch-Petersen, B., Cloos, L., Jensen, H.K., Tyrsted, G. Adv. Enzyme Regul. (1995) [Pubmed]
  19. Time course of enhanced activity of deoxycytidine kinase and thymidine kinase 1 and 2 in cultured human squamous lung carcinoma cells, SW-1573, induced by gamma-irradiation. Haveman, J., Sigmond, J., van Bree, C., Franken, N.A., Koedooder, C., Peters, G.J. Oncol. Rep. (2006) [Pubmed]
  20. Integration of transcript and genetic maps of chromosome 16 at near-1-Mb resolution: demonstration of a "hot spot" for recombination at 16p12. Callen, D.F., Lane, S.A., Kozman, H., Kremmidiotis, G., Whitmore, S.A., Lowenstein, M., Doggett, N.A., Kenmochi, N., Page, D.C., Maglott, D.R. Genomics (1995) [Pubmed]
  21. Diverging substrate specificity of pure human thymidine kinases 1 and 2 against antiviral dideoxynucleosides. Munch-Petersen, B., Cloos, L., Tyrsted, G., Eriksson, S. J. Biol. Chem. (1991) [Pubmed]
  22. 2', 3'-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T-lymphoid cells. Han, T., Fernandez, M., Sarkar, M., Agarwal, R.P. Life Sci. (2004) [Pubmed]
  23. Enzyme kinetics of thymidine kinase isoenzymes of Ehrlich ascites tumour. He, Q.M., Skog, S., Welander, I., Tribukait, B. Anticancer Res. (1990) [Pubmed]
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