Thymidine kinase 1

"TK1" redirects here. For the video game, see Tekken (video game).

TK1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1W4R, 1XBT, 2ORV, 2WVJ
Identifiers
Aliases	TK1 , TK2, Thymidine kinase 1
External IDs	OMIM: 188300; MGI: 98763; HomoloGene: 37749; GeneCards: TK1; OMA:TK1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q25.3 Start 78,174,091 bp [1] End 78,187,233 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 E2|11 82.96 cM Start 117,706,352 bp [2] End 117,716,918 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon gonad stromal cell of endometrium mucosa of esophagus ventricular zone bone marrow ganglionic eminence rectum bone marrow cells oral cavity Top expressed in blastocyst fetal liver hematopoietic progenitor cell morula ventricular zone otic vesicle tibiofemoral joint mandibular prominence maxillary prominence dermis otic placode More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding nucleoside kinase activity zinc ion binding metal ion binding kinase activity protein binding identical protein binding ATP binding thymidine kinase thymidine kinase activity Cellular component cytoplasm cytosol Biological process DNA biosynthetic process phosphorylation pyrimidine nucleoside salvage nucleobase-containing compound metabolic process protein homotetramerization deoxyribonucleoside monophosphate biosynthetic process DNA metabolic process nucleotide biosynthetic process thymidine metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7083 21877 Ensembl ENSG00000167900 ENSMUSG00000025574 UniProt P04183 P04184 RefSeq (mRNA) NM_003258 NM_001346663 NM_001363848 NM_001271729 NM_009387 RefSeq (protein) NP_001333592 NP_003249 NP_001350777 NP_001258658 NP_033413 Location (UCSC) Chr 17: 78.17 – 78.19 Mb Chr 11: 117.71 – 117.72 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Thymidine kinase 1, soluble (gene name TK1), is a human thymidine kinase. ^[5]

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.

Interactions

Thymidine kinase 1 has been shown to interact with P21. ^[6]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Thymidine Kinase 1 in Cancer

Elevations in serum TK-1 have been found to correlate with the return of breast and other forms of cancer ^[7] TK-1 can be used to detect cancer earlier, determine what stage it is in, and detect recurrence. Thymidine Kinase 1 can be measured based on its enzyme activity ^[8] or using immunoassay. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000167900 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025574 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Thymidine kinase 1, soluble".
6. Huang DY, Chang ZF (June 2001). "Interaction of human thymidine kinase 1 with p21(Waf1)". Biochem. J. 356 (Pt 3): 829–34. doi:10.1042/0264-6021:3560829. PMC   1221910 . PMID   11389691.
7. Alegre MM, Robison RA, O'Neill KL (2012). "Thymidine kinase 1 up-regulation is an early event in breast tumor formation". Journal of Oncology. 2012: 575647. doi: 10.1155/2012/575647 . PMC   3388419 . PMID   22778736.
8. Munch-Petersen B (2005). "Differences in the kinetic properties of thymidine kinase isoenzymes in unstimulated and phytohemagglutinin-stimulated human lymphocytes". Mol. Cell. Biochem. 64 (2): 1013–19. doi:10.1007/BF00224774. PMID   6504022. S2CID   11326439.
9. He Q, Zhang P, Zou L, et al. (2005). "Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity". Oncol. Rep. 14 (4): 1013–19. PMID   16142366.

Further reading

• 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. doi: 10.1016/S0021-9258(18)45939-X . PMID   1370831.
• Barik S, Banerjee AK (1991). "Cloning and expression of the vesicular stomatitis virus phosphoprotein gene in Escherichia coli: analysis of phosphorylation status versus transcriptional activity". J. Virol. 65 (4): 1719–26. doi:10.1128/JVI.65.4.1719-1726.1991. PMC   239976 . PMID   1848304.
• Sadava D, Bernard B (1990). "Transition from cytosolic to mitochondrial thymidine kinase during development in human fetal tissues". Life Sci. 47 (25): 2359–64. doi:10.1016/0024-3205(90)90275-V. PMID   2263164.
• 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. PMID   2538159.
• 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. doi: 10.1093/oxfordjournals.molbev.a040422 . PMID   3128713.
• 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. PMID   3301530.
• 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. doi: 10.1016/S0021-9258(19)57403-8 . PMID   3335503.
• Kreidberg JA, Kelly TJ (1986). "Genetic analysis of the human thymidine kinase gene promoter". Mol. Cell. Biol. 6 (8): 2903–9. doi:10.1128/mcb.6.8.2903. PMC   367858 . PMID   3785218.
• Bradshaw HD, Deininger PL (1984). "Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells". Mol. Cell. Biol. 4 (11): 2316–20. doi:10.1128/mcb.4.11.2316. PMC   369060 . PMID   6549046.
• 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. PMID   8786092. S2CID   9056186.
• 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 . PMID   9575153.
• 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 . PMID   10924519.
• Huang DY, Chang ZF (2001). "Interaction of human thymidine kinase 1 with p21(Waf1)". Biochem. J. 356 (Pt 3): 829–34. doi:10.1042/0264-6021:3560829. PMC   1221910 . PMID   11389691.
• 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. PMID   11474248. S2CID   9006108.
• 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 . PMID   11992400. S2CID   23856606.
• 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. PMID   12449723. S2CID   23072666.
• 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. doi:10.5301/jbm.2008.2452. PMID   12699056.
• 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. PMID   14659972.
• 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. PMID   14697231.
• ONeill KL, Buckwalter M, Murray BK (2001). "Thymidine kinase: diagnostic and prognostic potential". Expert Rev. Mol. Diagn. 1 (4): 428–33. doi:10.1586/14737159.1.4.428. PMID   11901857. S2CID   12790327.
• Topolcan O, Holubec Jr L (2008). "The role of thymidine kinase in cancer diseases". Expert Opin. Med. Diagn. 2 (2): 129–41. doi:10.1517/17530059.2.2.129. PMID   23485133.
• Jagarlamudi KK, Shaw M (2018). "Thymidine Kinase 1 as a Tumor Biomarker: Technical Advances offer New Potential to an Old Biomarker". Biomark. Med. 12 (9): 1035–48. doi: 10.2217/bmm-2018-0157 . PMID   30039979.