Two forms of this protein have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells.
Thymidine kinase has been making a growing impact in the cancer research community. It has been found that elevated blood serum levels of TK-1 correlates with metastatic capabilities of the cancer and thereby can be used to detect malignant types of cancer, furthermore TK-1 has been found to show up in blood serum even before clinical symptoms even start to show. This would allow quicker treatment before the cancer becomes too developed. TK-1 has also been found to correlate with the return of breast cancer along with many more types of cancer. TK-1 can be used to detect cancer earlier, determine what stage it is in, and if in remission it can be used to predict another cancer growth event. Attempts to make commercial ELISA tests to test blood serum levels have not been promising.
Kim YK, Lee AS (1992). "Identification of a protein-binding site in the promoter of the human thymidine kinase gene required for the G1-S-regulated transcription". J. Biol. Chem. 267 (4): 2723–7. PMID1370831.
Tamiya N, Yusa T, Yamaguchi Y, Tsukifuji R, Kuroiwa N, Moriyama Y, Fujimura S (1989). "Co-purification of thymidylate kinase and cytosolic thymidine kinase from human term placenta by affinity chromatography". Biochim. Biophys. Acta. 995 (1): 28–35. doi:10.1016/0167-4838(89)90229-X. PMID2538159.
Slagel V, Flemington E, Traina-Dorge V, Bradshaw H, Deininger P (1987). "Clustering and subfamily relationships of the Alu family in the human genome". Mol. Biol. Evol. 4 (1): 19–29. PMID3128713.
Flemington E, Bradshaw HD, Traina-Dorge V, Slagel V, Deininger PL (1987). "Sequence, structure and promoter characterization of the human thymidine kinase gene". Gene. 52 (2-3): 267–77. doi:10.1016/0378-1119(87)90053-9. PMID3301530.
Sherley JL, Kelly TJ (1988). "Human cytosolic thymidine kinase. Purification and physical characterization of the enzyme from HeLa cells". J. Biol. Chem. 263 (1): 375–82. PMID3335503.
Kuo WL, Hirschhorn R, Huie ML, Hirschhorn K (1996). "Localization and ordering of acid alpha-glucosidase (GAA) and thymidine kinase (TK1) by fluorescence in situ hybridization". Hum. Genet. 97 (3): 404–6. doi:10.1007/BF02185782. PMID8786092.
Chang ZF, Huang DY, Chi LM (1998). "Serine 13 is the site of mitotic phosphorylation of human thymidine kinase". J. Biol. Chem. 273 (20): 12095–100. doi:10.1074/jbc.273.20.12095. PMID9575153.
Berenstein D, Christensen JF, Kristensen T, Hofbauer R, Munch-Petersen B (2000). "Valine, not methionine, is amino acid 106 in human cytosolic thymidine kinase (TK1). Impact on oligomerization, stability, and kinetic properties". J. Biol. Chem. 275 (41): 32187–92. doi:10.1074/jbc.M005325200. PMID10924519.
Fujiwaki R, Hata K, Moriyama M, Iwanari O, Katabuchi H, Okamura H, Miyazaki K (2001). "Clinical value of thymidine kinase in patients with cervical carcinoma". Oncology. 61 (1): 47–54. doi:10.1159/000055352. PMID11474248.
Fujiwaki R, Hata K, Nakayama K, Moriyama M, Iwanari O, Katabuchi H, Okamura H, Sakai E, Miyazaki K (2002). "Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes". Int. J. Cancer. 99 (3): 328–35. doi:10.1002/ijc.10319. PMID11992400.
Mao Y, Wu J, Wang N, He L, Wu C, He Q, Skog S (2002). "A comparative study: immunohistochemical detection of cytosolic thymidine kinase and proliferating cell nuclear antigen in breast cancer". Cancer Invest. 20 (7-8): 922–31. doi:10.1081/CNV-120005905. PMID12449723.
Gilles SI, Romain S, Casellas P, Ouafik L, Fina F, Combes T, Vuaroquaux V, Seitz JF, Bonnier P, Galiègue S, Carayon P, Martin PM (2003). "Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer". Int. J. Biol. Markers. 18 (1): 1–6. PMID12699056.
Han T, Fernandez M, Sarkar M, Agarwal RP (2004). "2', 3'-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T-lymphoid cells". Life Sci. 74 (7): 835–42. doi:10.1016/j.lfs.2003.07.023. PMID14659972.
Li CL, Lu CY, Ke PY, Chang ZF (2004). "Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site". Biochem. Biophys. Res. Commun. 313 (3): 587–93. doi:10.1016/j.bbrc.2003.11.147. PMID14697231.