HGNC Approved Gene Symbol: TK1
Cytogenetic location: 17q25.3 Genomic coordinates (GRCh38): 17:78,174,079-78,187,204 (from NCBI)
Thymidine kinase (EC 2.7.1.21) catalyzes the phosphorylation of thymidine to deoxythymidine monophosphate.
Lin et al. (1983) cloned the TK1 gene.
Sherley and Kelly (1988) purified and characterized the enzyme from HeLa cells.
Lin et al. (1983) estimated that the maximal size of the TK1 gene is 14 kb and its minimal size between 4 and 5 kb. The gene contains many noncoding inserts and numerous Alu sequences. Nucleotide sequencing indicated considerable evolutionary conservation of the TK gene; Bradshaw and Deininger (1984) found about 70% homology between the human and chicken genes.
Flemington et al. (1987) sequenced the entire 12.9-kb human TK gene, along with flanking regions. TK is composed of 7 exons. Within the introns, 13 Alu family repeated sequences and a polypyrimidine stretch were found.
In the 5-prime flanking region of the TK gene, Sauve et al. (1990) located the position of nucleotide sequences that can act as binding sites for transacting factors as well as potential cis-acting sequences. The latter were compared with those of the promoter of the human PCNA gene (176740). Both TK and PCNA are maximally expressed at the G1/S boundary of the cell cycle.
Weiss and Green (1967) found that fusion of mouse cells lacking this enzyme with normal human cells could be achieved, that progressive loss of human chromosomes from the hybrid occurred with passage of time, and that at a stage when only one human chromosome remained the cell still had the capacity to synthesize thymidine kinase. The assumption was that the remaining chromosome, now identified as chromosome 17 (Migeon and Miller, 1968; Miller et al., 1971), carries the TK locus. Boone et al. (1972) presented evidence that TK is on the long arm of chromosome 17. McDougall et al. (1973) showed that adeno-12 virus causes a gap in the long arm of chromosome 17. Since the adeno-12 virus causes a 2- or 3-fold increase in TK, the gap may represent the TK locus and may be comparable to a puff.
By study of an 11-17 translocation in mouse-man hybrid cells, Francke and Busby (1974) located the TK locus to the region distal to q21.
In the African green monkey, the thymidine kinase and galactokinase (604313) loci are both on a chromosome similar to human E-17 in size, shape and Giemsa banding pattern (Croce et al., 1974). This is another striking example of chromosomal homology.
Kucherlapati et al. (1974) assigned the TK1 locus to 17q21-q22. By chromosome-mediated gene transfer (CMGT), Klobutcher and Ruddle (1979) transferred the genes for thymidine kinase, galactokinase, and type I procollagen (120150). The data indicated the following gene order: cen--GALK--(TK1--COL1A1). Studies by vanTuinen and Ledbetter (1987) led to the conclusion that TK is located in the segment 17q23-qter, which is consistent with the conclusion of Sparkes et al. (1986). Xu et al. (1988) mapped the TK locus to 17q23-q25 by in situ hybridization. Xu et al. (1988) also used CMGT in the generation of a physical map of chromosome 17. This is an established method of constructing hybrid cells containing subchromosomal fragments of a selected donor chromosome. The generation of transfectants for chromosome 17 is helped by the presence of the selectable marker TK. Xu et al. (1988) generated a panel of more than 50 transfectants containing different transgenomic fragments of chromosome 17. By analyzing cotransfection frequencies, Xu et al. (1988) found groups of loci that are closely situated on chromosome 17. Their results confirmed, however, that although substantial lengths of DNA may be transferred intact, interstitial deletions occur frequently. Furthermore, multiple fragments of transfected chromatin can be found in the same clone, and there is selection for centromeric sequences. Their overall results indicated the following order: pter--(TP53--POLR2--D17S1)--(MYHSA2--MYHSA1)--D17Z1--CRYB1-- (ERBA1--GCSF--NGL)--acute promyelocytic leukemia breakpoint--RNU2--HOX2-- (NGFR--COL1A1--MPO)--GAA--UMPH--GHC--TK1--GALK--qter. By fluorescence in situ hybridization, Kuo et al. (1996) mapped both GAA (232300) and the thymidine kinase gene to 17q25.2-q25.3 and showed that GAA is distal to TK1.
Boone, C., Chen, T.-R., Ruddle, F. H. Assignment of three human genes to chromosomes (LHD-A to 11, TK to 17, and IDH to 20) and evidence for translocation between human and mouse chromosomes in somatic cell hybrids. Proc. Nat. Acad. Sci. 69: 510-514, 1972. [PubMed: 4110482] [Full Text: https://doi.org/10.1073/pnas.69.2.510]
Bradshaw, H. D., Jr., Deininger, P. L. Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells. Molec. Cell. Biol. 4: 2316-2320, 1984. [PubMed: 6549046] [Full Text: https://doi.org/10.1128/mcb.4.11.2316-2320.1984]
Chen, S.-H., McDougall, J. K., Creagan, R. P., Lewis, V., Ruddle, F. H. Genetic homology between man and the chimpanzee: syntenic relationships of genes for galactokinase and thymidine kinase and adenovirus-12-induced gaps using chimpanzee-mouse somatic cell hybrids. Somat. Cell Genet. 2: 205-214, 1976. [PubMed: 195354] [Full Text: https://doi.org/10.1007/BF01538959]
Creau-Goldberg, N., Turleau, C., Cochet, C., Huerre, C., Junien, C., de Grouchy, J. Conservation of the human COL1A1-TK-GAA synteny and homoeologous assignment in the African green monkey and the baboon (Cercopithecoidae). Hum. Genet. 68: 333-336, 1984. [PubMed: 6096258] [Full Text: https://doi.org/10.1007/BF00292595]
Croce, C. M., Huebner, K., Koprowski, H. Chromosome assignment of the T-antigen gene of simian virus 40 in African green monkey cells transformed by adeno 7-SV40 hybrid. Proc. Nat. Acad. Sci. 71: 4116-4119, 1974. [PubMed: 4372607] [Full Text: https://doi.org/10.1073/pnas.71.10.4116]
Flemington, E., Bradshaw, H. D., Jr., Traina-Dorge, V., Slagel, V., Deininger, P. L. Sequence, structure and promoter characterization of the human thymidine kinase gene. Gene 52: 267-277, 1987. [PubMed: 3301530] [Full Text: https://doi.org/10.1016/0378-1119(87)90053-9]
Francke, U., Busby, N. Intrachromosomal mapping of human thymidine kinase locus. (Abstract) Clin. Res. 22: 217A, 1974.
Ishizaki, K., Omoto, K., Sekiguchi, T. Confirmation of the assignment of the chimpanzee thymidine kinase and galactokinase genes to chromosome 19. Hum. Genet. 37: 231-234, 1977. [PubMed: 195892] [Full Text: https://doi.org/10.1007/BF00393586]
Klobutcher, L. A., Ruddle, F. H. Phenotype stabilisation and integration of transferred material in chromosome-mediated gene transfer. Nature 280: 657-660, 1979. [PubMed: 471042] [Full Text: https://doi.org/10.1038/280657a0]
Kozak, C. A., Ruddle, F. H. Assignment of genes for thymidine kinase and galactokinase to Mus-Musculus chromosome-11 and preferential segregation of this chromosome in Chinese hamster-mouse somatic cell hybrids. Somat. Cell Genet. 3: 121-134, 1977. [PubMed: 204065] [Full Text: https://doi.org/10.1007/BF01551809]
Kucherlapati, R., McDougall, J. K., Ruddle, F. H. Regional localization of the human genes for thymidine kinase, lactate dehydrogenase-A and esterase-A4. Cytogenet. Cell Genet. 13: 108-110, 1974. [PubMed: 4827473] [Full Text: https://doi.org/10.1159/000130249]
Kuo, W.-L., Hirschhorn, R., Huie, M. L., Hirschhorn, K. Localization and ordering of acid alpha-glucosidase (GAA) and thymidine kinase (TK1) by fluorescence in situ hybridization. Hum. Genet. 97: 404-406, 1996. [PubMed: 8786092] [Full Text: https://doi.org/10.1007/BF02185782]
Lin, P.-F., Zhao, S.-Y., Ruddle, F. H. Genomic cloning and preliminary characterization of the human thymidine kinase gene. Proc. Nat. Acad. Sci. 80: 6528-6532, 1983. [PubMed: 6314329] [Full Text: https://doi.org/10.1073/pnas.80.21.6528]
McBreen, P., Orkwiszewski, K. G., Chern, C. J., Mellman, W. J., Croce, C. M. Synteny of the genes for thymidine kinase and galactokinase in the mouse and their assignment to mouse chromosome 11. Cytogenet. Cell Genet. 19: 7-13, 1977. [PubMed: 196814] [Full Text: https://doi.org/10.1159/000130789]
McBride, O. W., Burch, J. W., Ruddle, F. H. Cotransfer of thymidine kinase and galactokinase genes by chromosome-mediated gene transfer. Proc. Nat. Acad. Sci. 75: 914-918, 1978. [PubMed: 204939] [Full Text: https://doi.org/10.1073/pnas.75.2.914]
McDougall, J. K., Kucherlapati, R. S., Ruddle, F. H. Localization and induction of the human thymidine kinase gene by adenovirus 12. Nature N.B. 245: 172-175, 1973. [PubMed: 4126392] [Full Text: https://doi.org/10.1038/newbio245172a0]
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Migeon, B. R., Miller, C. S. Human-mouse somatic cell hybrids with single human chromosome (group E): link with thymidine kinase activity. Science 162: 1005-1006, 1968. [PubMed: 5698836] [Full Text: https://doi.org/10.1126/science.162.3857.1005]
Miller, O. J., Allderdice, P. W., Miller, D. A. Human thymidine kinase gene locus: assignment to chromosome 17 in a hybrid of man and mouse cells. Science 173: 244-245, 1971. [PubMed: 5104177] [Full Text: https://doi.org/10.1126/science.173.3993.244]
Murphy, P. D., Kidd, J. R., Castiglione, C. M., Lin, P. F., Ruddle, F. H., Kidd, K. K. A frequent polymorphism for the cytosolic thymidine kinase gene, TK1, (17q21-q22) detected by the enzyme TaqI. Nucleic Acids Res. 14: 4381, 1986. [PubMed: 3012471] [Full Text: https://doi.org/10.1093/nar/14.10.4381]
Orkwiszewski, K. G., Tedesco, T. A., Mellman, W. J., Croce, C. M. Linkage relationship between the genes for thymidine kinase and galactokinase in different primates. Somat. Cell Genet. 2: 21-26, 1976. [PubMed: 195352] [Full Text: https://doi.org/10.1007/BF01539239]
Sauve, G. J., Lipson, K. E., Chen, S.-T., Baserga, R. Sequence analysis of the human thymidine kinase gene promoter: comparison with the human PCNA promoter. DNA Seq. 1: 13-23, 1990. [PubMed: 1983453] [Full Text: https://doi.org/10.3109/10425179009041343]
Sherley, J. L., Kelly, T. J. Human cytosolic thymidine kinase: purification and physical characterization of the enzyme from HeLa cells. J. Biol. Chem. 263: 375-382, 1988. [PubMed: 3335503]
Sparkes, R. S., Mohandas, T., Heinzmann, C., Gorin, M. B., Zollman, S., Horwitz, J. Assignment of a human beta-crystallin gene to 17cen-q23. Hum. Genet. 74: 133-136, 1986. [PubMed: 3770741] [Full Text: https://doi.org/10.1007/BF00282076]
vanTuinen, P., Ledbetter, D. H. Construction and utilization of a detailed somatic cell hybrid mapping panel for human chromosome 17: localization of an anonymous clone to the critical region of Miller-Dieker syndrome, deletion 17p13. (Abstract) Cytogenet. Cell Genet. 46: 708-709, 1987.
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Weiss, M., Green, H. Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes. Proc. Nat. Acad. Sci. 58: 1104-1111, 1967. [PubMed: 5233838] [Full Text: https://doi.org/10.1073/pnas.58.3.1104]
Xu, W., Gorman, P. A., Rider, S. H., Hedge, P. J., Moore, G., Prichard, C., Sheer, D., Solomon, E. Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer. Proc. Nat. Acad. Sci. 85: 8563-8567, 1988. [PubMed: 3186746] [Full Text: https://doi.org/10.1073/pnas.85.22.8563]