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Gene Review

DTYMK  -  deoxythymidylate kinase (thymidylate kinase)

Homo sapiens

Synonyms: CDC8, PP3731, TMPK, TYMK, Thymidylate kinase, ...
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Disease relevance of DTYMK

  • In contrast, active human dTMP kinase can be expressed from the gene cloned into the baculovirus expression system, as evidenced by increased enzymatic activity by four- to five-fold [1].
  • We have also examined four neuroblastoma cell lines for dTMP kinase mRNA levels and its kinase activities, which appear to vary according to cell growth rate [1].
  • The nucleotide sequence of the cloned human cDNA is predicted to encode a 24 KD protein that shows considerable homology with the yeast and vaccinia virus dTMP kinase enzymes [2].
  • Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography [3].
  • Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway [4].

High impact information on DTYMK


Chemical compound and disease context of DTYMK


Biological context of DTYMK

  • Our results show the drastic effects that slight modifications of the substrates exert on the enzyme's conformation and, hence, activity and suggest the type of substitutions that are compatible with efficient phosphorylation by TMPK [13].
  • The levels of dTMP kinase mRNA and its enzymatic activity fluctuate during the cell cycle, peaking at the S phase [1].
  • Our results suggest that the expression of the dTMP kinase gene and its activity coincide with various stages of cell growth [1].
  • Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth [1].
  • Thymidylate kinase could utilize either ATP or dATP as an efficient phosphate donor, and showed substrate specificity for dTMP [14].

Anatomical context of DTYMK

  • It was demonstrated that in this species, in contrast to a number of Acetabulariae, thymidylate kinase is translated on 70 S ribosomes [15].
  • Therefore, it appears that low levels of thymidine phosphorylation suffice to fulfill the role of the viral enzyme in ganglia and that this role can be partially fulfilled by thymidylate kinase activity alone [16].
  • We examined the effect of ethanol and a combination of ethanol and AZT on TK and TMPK activities in human Jurkat T cells [17].
  • Inhibition of tumour growth is accompanied by a reduction of dThd, dGuo and dTMP kinase activities in tumour cytosol (by 91% and 74% and 55%, respectively) and decrease in contents of dTTP, dGTP and dATP (by 92%, 77% and 67%, respectively) in dNTP pool [18].

Associations of DTYMK with chemical compounds


Other interactions of DTYMK


Analytical, diagnostic and therapeutic context of DTYMK


  1. Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth. Huang, S.H., Tang, A., Drisco, B., Zhang, S.Q., Seeger, R., Li, C., Jong, A. DNA Cell Biol. (1994) [Pubmed]
  2. Molecular cloning and expression of the human deoxythymidylate kinase gene in yeast. Su, J.Y., Sclafani, R.A. Nucleic Acids Res. (1991) [Pubmed]
  3. Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. Lee, L.S., Cheng, Y. J. Biol. Chem. (1977) [Pubmed]
  4. Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway. Fioravanti, E., Haouz, A., Ursby, T., Munier-Lehmann, H., Delarue, M., Bourgeois, D. J. Mol. Biol. (2003) [Pubmed]
  5. AZT monophosphate knocks thymidylate kinase for a loop. Kenyon, G.L. Nat. Struct. Biol. (1997) [Pubmed]
  6. Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Furman, P.A., Fyfe, J.A., St Clair, M.H., Weinhold, K., Rideout, J.L., Freeman, G.A., Lehrman, S.N., Bolognesi, D.P., Broder, S., Mitsuya, H. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  7. Elevation of dihydrofolate reductase, thymidylate synthetase, and thymidine kinase in cultured mammalian cells after exposure to folate antagonists. Chello, P.L., McQueen, C.A., DeAngelis, L.M., Bertino, J.R. Cancer Res. (1976) [Pubmed]
  8. Spectrum of antiviral activity and mechanism of action of zidovudine. An overview. Furman, P.A., Barry, D.W. Am. J. Med. (1988) [Pubmed]
  9. X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution. Li de la Sierra, I., Munier-Lehmann, H., Gilles, A.M., Bârzu, O., Delarue, M. J. Mol. Biol. (2001) [Pubmed]
  10. Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir. Gustafson, E.A., Schinazi, R.F., Fingeroth, J.D. J. Virol. (2000) [Pubmed]
  11. Kinetics of the interaction of monophosphates of the antiviral nucleosides 2'-fluoro-1-beta-D-arabinofuranosylpyrimidine and (E)-5-(2-bromovinyl)-2'-deoxyuridine with thymidylate kinases from Vero cells and herpes simplex virus types 1 and 2. Chen, M.S., Amico, L.A., Speelman, D.J. Antimicrob. Agents Chemother. (1984) [Pubmed]
  12. Metabolic fate of (E)-5-(2-bromovinyl)-2'-deoxyuridine in herpes simplex virus- and mock-infected cells. Ayisi, N.K., De Clercq, E., Wall, R.A., Hughes, H., Sacks, S.L. Antimicrob. Agents Chemother. (1984) [Pubmed]
  13. Structures of human thymidylate kinase in complex with prodrugs: implications for the structure-based design of novel compounds. Ostermann, N., Segura-Peña, D., Meier, C., Veit, T., Monnerjahn, C., Konrad, M., Lavie, A. Biochemistry (2003) [Pubmed]
  14. Co-purification of thymidylate kinase and cytosolic thymidine kinase from human term placenta by affinity chromatography. Tamiya, N., Yusa, T., Yamaguchi, Y., Tsukifuji, R., Kuroiwa, N., Moriyama, Y., Fujimura, S. Biochim. Biophys. Acta (1989) [Pubmed]
  15. Possible translocation of a gene for thymidylate kinase from the chloroplast to the nuclear genome during evolution. de Groot, E.J., Schweiger, H.G. J. Cell. Sci. (1984) [Pubmed]
  16. Human thymidine kinase can functionally replace herpes simplex virus type 1 thymidine kinase for viral replication in mouse sensory ganglia and reactivation from latency upon explant. Chen, S.H., Cook, W.J., Grove, K.L., Coen, D.M. J. Virol. (1998) [Pubmed]
  17. Ethanol decreases the efficiency of phosphorylation of thymidine kinase in a human T-lymphocytic cell line. Prakash, O., Tang, Z.Y., Zhou, P., Peng, X., Kolls, J., Shellito, J.E., Nelson, S. Alcohol. Clin. Exp. Res. (2002) [Pubmed]
  18. Growth inhibition of Kirkman-Robbins hepatoma by 1-(1,3-dihydroxy-2-propoxymethyl)-5,6-tetramethyleneuracil and possible mechanism of its biological activity. Greger, J., Dramiński, M. Z. Naturforsch., C, J. Biosci. (1989) [Pubmed]
  19. Metabolism of 4'-azidothymidine. A compound with potent and selective activity against the human immunodeficiency virus. Chen, M.S., Suttmann, R.T., Wu, J.C., Prisbe, E.J. J. Biol. Chem. (1992) [Pubmed]
  20. Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases. Van Rompay, A.R., Johansson, M., Karlsson, A. Pharmacol. Ther. (2000) [Pubmed]
  21. Decrease in thymidylate kinase activity in peripheral blood mononuclear cells from HIV-infected individuals. Jacobsson, B., Britton, S., Törnevik, Y., Eriksson, S. Biochem. Pharmacol. (1998) [Pubmed]
  22. Thymidylate kinase from Acetabularia. I. Properties of the enzyme. de Groot, E.J., Schweiger, H.G. J. Cell. Sci. (1983) [Pubmed]
  23. DNA-synthesizing enzymes in breast cancer (thymidine kinase, thymidylate synthase and thymidylate kinase): association with flow cytometric S-phase fraction and relative prognostic importance in node-negative premenopausal patients. Romain, S., Bendahl, P.O., Guirou, O., Malmström, P., Martin, P.M., Fernö, M. Int. J. Cancer (2001) [Pubmed]
  24. Bacterial evolution and silicon. Trevors, J.T. Antonie Van Leeuwenhoek (1997) [Pubmed]
  25. Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. Reyes, P., Rathod, P.K., Sanchez, D.J., Mrema, J.E., Rieckmann, K.H., Heidrich, H.G. Mol. Biochem. Parasitol. (1982) [Pubmed]
  26. Increased uptake of thymidine in the activation of sea urchin eggs. II. Cooperativity with phosphorylation, involvement of the cortex, and partial localization of the kinases. McGwin, N.F., Morton, R.W., Nishioka, D. Exp. Cell Res. (1983) [Pubmed]
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