ID KITH_HUMAN Reviewed; 234 AA. AC P04183; B2RC58; Q969V0; Q9UMG9; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 19-SEP-2002, sequence version 2. DT 27-MAR-2024, entry version 224. DE RecName: Full=Thymidine kinase, cytosolic {ECO:0000305}; DE EC=2.7.1.21 {ECO:0000269|PubMed:14697231, ECO:0000269|PubMed:22385435}; GN Name=TK1 {ECO:0000312|HGNC:HGNC:11830}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6549046; DOI=10.1128/mcb.4.11.2316-2320.1984; RA Bradshaw H.D. Jr., Deininger P.L.; RT "Human thymidine kinase gene: molecular cloning and nucleotide sequence of RT a cDNA expressible in mammalian cells."; RL Mol. Cell. Biol. 4:2316-2320(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3301530; DOI=10.1016/0378-1119(87)90053-9; RA Flemington E., Bradshaw H.D. Jr., Traina-Dorge V., Slagel V., RA Deininger P.L.; RT "Sequence, structure and promoter characterization of the human thymidine RT kinase gene."; RL Gene 52:267-277(1987). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph, Skin, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. RX PubMed=3785218; DOI=10.1128/mcb.6.8.2903-2909.1986; RA Kreidberg J.A., Kelly T.J.; RT "Genetic analysis of the human thymidine kinase gene promoter."; RL Mol. Cell. Biol. 6:2903-2909(1986). RN [7] RP PHOSPHORYLATION AT SER-13, AND MUTAGENESIS OF SER-13 AND SER-194. RX PubMed=9575153; DOI=10.1074/jbc.273.20.12095; RA Chang Z.F., Huang D.Y., Chi L.M.; RT "Serine 13 is the site of mitotic phosphorylation of human thymidine RT kinase."; RL J. Biol. Chem. 273:12095-12100(1998). RN [8] RP FUNCTION, PHOSPHORYLATION AT SER-13, MUTAGENESIS OF SER-13, CATALYTIC RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT. RX PubMed=14697231; DOI=10.1016/j.bbrc.2003.11.147; RA Li C.L., Lu C.Y., Ke P.Y., Chang Z.F.; RT "Perturbation of ATP-induced tetramerization of human cytosolic thymidine RT kinase by substitution of serine-13 with aspartic acid at the mitotic RT phosphorylation site."; RL Biochem. Biophys. Res. Commun. 313:587-593(2004). RN [9] RP FUNCTION, DEVELOPMENTAL STAGE, UBIQUITINATION, MUTAGENESIS OF SER-13; RP 203-LYS--ASN-205; 203-LYS-GLU-204 AND LYS-203, INTERACTION WITH FZR1, AND RP DOMAIN. RX PubMed=14701726; DOI=10.1128/mcb.24.2.514-526.2004; RA Ke P.Y., Chang Z.F.; RT "Mitotic degradation of human thymidine kinase 1 is dependent on the RT anaphase-promoting complex/cyclosome-CDH1-mediated pathway."; RL Mol. Cell. Biol. 24:514-526(2004). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-231, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-13, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-193 IN COMPLEX WITH ZINC IONS RP AND TTP, AND SUBUNIT. RX PubMed=15611477; DOI=10.1073/pnas.0406332102; RA Welin M., Kosinska U., Mikkelsen N.E., Carnrot C., Zhu C., Wang L., RA Eriksson S., Munch-Petersen B., Eklund H.; RT "Structures of thymidine kinase 1 of human and mycoplasmic origin."; RL Proc. Natl. Acad. Sci. U.S.A. 101:17970-17975(2004). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 15-194 IN COMPLEX WITH ZINC IONS RP AND TTP. RX PubMed=15733844; DOI=10.1016/j.febslet.2005.01.034; RA Birringer M.S., Claus M.T., Folkers G., Kloer D.P., Schulz G.E., RA Scapozza L.; RT "Structure of a type II thymidine kinase with bound dTTP."; RL FEBS Lett. 579:1376-1382(2005). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH ZINC IONS; SUBSTRATE RP AND ATP ANALOG, AND SUBUNIT. RX PubMed=17407781; DOI=10.1016/j.jmb.2007.02.104; RA Segura-Pena D., Lutz S., Monnerjahn C., Konrad M., Lavie A.; RT "Binding of ATP to TK1-like enzymes is associated with a conformational RT change in the quaternary structure."; RL J. Mol. Biol. 369:129-141(2007). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-193 OF MUTANT SER-163, RP ZINC-BINDING SITES, MUTAGENESIS OF MET-28; LEU-124 AND THR-163, CATALYTIC RP ACTIVITY, FUNCTION, AND SUBUNIT. RX PubMed=22385435; DOI=10.1111/j.1742-4658.2012.08554.x; RA Skovgaard T., Uhlin U., Munch-Petersen B.; RT "Comparative active-site mutation study of human and Caenorhabditis elegans RT thymidine kinase 1."; RL FEBS J. 279:1777-1787(2012). CC -!- FUNCTION: Cell-cycle-regulated enzyme of importance in nucleotide CC metabolism (PubMed:9575153). Catalyzes the first enzymatic step in the CC salvage pathway converting thymidine into thymidine monophosphate CC (PubMed:22385435). Transcriptional regulation limits expression to the CC S phase of the cell cycle and transient expression coincides with the CC oscillation in the intracellular dTTP concentration (Probable). Also CC important for the activation of anticancer and antiviral nucleoside CC analog prodrugs such as 1-b-d-arabinofuranosylcytosine (AraC) and 3c- CC azido-3c-deoxythymidine (AZT) (PubMed:22385435). CC {ECO:0000269|PubMed:22385435, ECO:0000269|PubMed:9575153, CC ECO:0000305|PubMed:17407781}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + thymidine = ADP + dTMP + H(+); Xref=Rhea:RHEA:19129, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17748, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:63528, ChEBI:CHEBI:456216; EC=2.7.1.21; CC Evidence={ECO:0000269|PubMed:14697231, ECO:0000269|PubMed:22385435}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19130; CC Evidence={ECO:0000305|PubMed:14697231, ECO:0000305|PubMed:22385435}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.4 uM for thymidine {ECO:0000269|PubMed:22385435}; CC KM=0.54 uM for thymidine {ECO:0000269|PubMed:14697231}; CC KM=0.52 uM for AZT {ECO:0000269|PubMed:22385435}; CC Vmax=26.6 umol/min/mg enzyme toward thymidine CC {ECO:0000269|PubMed:22385435}; CC Vmax=10 umol/min/mg enzyme toward AZT {ECO:0000269|PubMed:22385435}; CC Note=Kcats are 9.5 sec(-1) and 3.5 sec(-1) with thymidine and AZT as CC substrates, respectively (PubMed:22385435). Kcat is 282 min(-1) with CC thymidine (PubMed:14697231). {ECO:0000269|PubMed:14697231, CC ECO:0000269|PubMed:22385435}; CC -!- SUBUNIT: Homotetramer (PubMed:15611477, PubMed:15733844, CC PubMed:17407781, PubMed:22385435, PubMed:14697231). Tetramerization CC from dimerization is induced by ATP and increases catalytic efficiency CC due to a high affinity for thymidine (PubMed:14697231). Tetramerization CC is inhibited by phosphorylation at Ser-13 (PubMed:14697231). Interacts CC (via the KEN box) with FZR1 (PubMed:14701726). CC {ECO:0000269|PubMed:14697231, ECO:0000269|PubMed:14701726, CC ECO:0000269|PubMed:15611477, ECO:0000269|PubMed:15733844, CC ECO:0000269|PubMed:17407781, ECO:0000269|PubMed:22385435}. CC -!- INTERACTION: CC P04183; P05067: APP; NbExp=3; IntAct=EBI-712550, EBI-77613; CC P04183; A0A087WZT3: BOLA2-SMG1P6; NbExp=3; IntAct=EBI-712550, EBI-12006120; CC P04183; Q92993: KAT5; NbExp=3; IntAct=EBI-712550, EBI-399080; CC P04183; Q1RN33: MAGEA4; NbExp=3; IntAct=EBI-712550, EBI-10194128; CC P04183; P04183: TK1; NbExp=2; IntAct=EBI-712550, EBI-712550; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- DEVELOPMENTAL STAGE: Significantly increased in the cells during CC progression to the S and M phases, and becomes barely detectable in the CC early G(1) phase by a proteolytic control during mitotic exit. CC {ECO:0000269|PubMed:14701726}. CC -!- DOMAIN: KEN box sequence located in the C-terminal region is required CC for its mitotic degradation by the APC/C-FZR1 ubiquitin ligase and CC interaction capability with FZR1. {ECO:0000269|PubMed:14701726}. CC -!- PTM: Phosphorylated on Ser-13 in mitosis. Phosphorylation of Ser-13 by CC CDK1 during mitosis reduces homotetramerization and catalytic CC efficiency when DNA replication is complete and intracellular TK1 is CC still present at a high level (PubMed:9575153, PubMed:14697231). CC {ECO:0000269|PubMed:14697231, ECO:0000269|PubMed:9575153}. CC -!- PTM: Polyubiquitinated. Postmitosis, ubiquitination leads to CC proteasomal degradation. The KEN box sequence located at the C-terminal CC region targets for degradation by the anaphase promoting complex CC (APC/C) activated and rate-limited by FZR1. CC {ECO:0000269|PubMed:14701726}. CC -!- MISCELLANEOUS: Two forms have been identified in animal cells, one in CC cytosol and one in mitochondria. Activity of the cytosolic enzyme is CC high in proliferating cells and peaks during the S-phase of the cell CC cycle; it is very low in resting cells. CC -!- SIMILARITY: Belongs to the thymidine kinase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; K02581; AAA61187.1; -; mRNA. DR EMBL; M15205; AAA61191.1; -; Genomic_DNA. DR EMBL; AK314950; BAG37455.1; -; mRNA. DR EMBL; BT006941; AAP35587.1; -; mRNA. DR EMBL; BC006484; AAH06484.1; -; mRNA. DR EMBL; BC007872; AAH07872.1; -; mRNA. DR EMBL; BC007986; AAH07986.1; -; mRNA. DR EMBL; M13643; AAA61189.1; -; Genomic_DNA. DR CCDS; CCDS11754.1; -. DR PIR; A27318; KIHUT. DR RefSeq; NP_003249.3; NM_003258.4. DR PDB; 1W4R; X-ray; 1.83 A; A/B/C/D/E/F/G/H=15-194. DR PDB; 1XBT; X-ray; 2.40 A; A/B/C/D/E/F/G/H=1-193. DR PDB; 2ORV; X-ray; 2.30 A; A/B=1-234. DR PDB; 2WVJ; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-193. DR PDBsum; 1W4R; -. DR PDBsum; 1XBT; -. DR PDBsum; 2ORV; -. DR PDBsum; 2WVJ; -. DR AlphaFoldDB; P04183; -. DR SMR; P04183; -. DR BioGRID; 112938; 237. DR IntAct; P04183; 179. DR MINT; P04183; -. DR STRING; 9606.ENSP00000468425; -. DR BindingDB; P04183; -. DR ChEMBL; CHEMBL2883; -. DR DrugBank; DB01692; Dithioerythritol. DR DrugBank; DB02452; Thymidine 5'-triphosphate. DR DrugBank; DB00432; Trifluridine. DR DrugBank; DB00495; Zidovudine. DR DrugCentral; P04183; -. DR GlyGen; P04183; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P04183; -. DR PhosphoSitePlus; P04183; -. DR BioMuta; TK1; -. DR DMDM; 23503074; -. DR EPD; P04183; -. DR jPOST; P04183; -. DR MassIVE; P04183; -. DR MaxQB; P04183; -. DR PaxDb; 9606-ENSP00000301634; -. DR PeptideAtlas; P04183; -. DR ProteomicsDB; 51674; -. DR Pumba; P04183; -. DR ABCD; P04183; 2 sequenced antibodies. DR Antibodypedia; 3322; 542 antibodies from 40 providers. DR DNASU; 7083; -. DR Ensembl; ENST00000301634.12; ENSP00000301634.6; ENSG00000167900.12. DR GeneID; 7083; -. DR KEGG; hsa:7083; -. DR MANE-Select; ENST00000301634.12; ENSP00000301634.6; NM_003258.5; NP_003249.3. DR UCSC; uc002juw.3; human. DR AGR; HGNC:11830; -. DR CTD; 7083; -. DR DisGeNET; 7083; -. DR GeneCards; TK1; -. DR HGNC; HGNC:11830; TK1. DR HPA; ENSG00000167900; Tissue enhanced (bone). DR MIM; 188300; gene. DR neXtProt; NX_P04183; -. DR OpenTargets; ENSG00000167900; -. DR PharmGKB; PA352; -. DR VEuPathDB; HostDB:ENSG00000167900; -. DR eggNOG; KOG3125; Eukaryota. DR GeneTree; ENSGT00390000011309; -. DR InParanoid; P04183; -. DR OMA; EAYEPRC; -. DR OrthoDB; 674053at2759; -. DR PhylomeDB; P04183; -. DR TreeFam; TF314839; -. DR BioCyc; MetaCyc:HS09657-MONOMER; -. DR BRENDA; 2.7.1.21; 2681. DR PathwayCommons; P04183; -. DR Reactome; R-HSA-69205; G1/S-Specific Transcription. DR Reactome; R-HSA-73614; Pyrimidine salvage. DR SABIO-RK; P04183; -. DR SignaLink; P04183; -. DR SIGNOR; P04183; -. DR BioGRID-ORCS; 7083; 26 hits in 1165 CRISPR screens. DR ChiTaRS; TK1; human. DR EvolutionaryTrace; P04183; -. DR GeneWiki; Thymidine_kinase_1; -. DR GenomeRNAi; 7083; -. DR Pharos; P04183; Tchem. DR PRO; PR:P04183; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P04183; Protein. DR Bgee; ENSG00000167900; Expressed in endometrium epithelium and 127 other cell types or tissues. DR ExpressionAtlas; P04183; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:GOC. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004797; F:thymidine kinase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:1904860; P:DNA synthesis involved in mitotic DNA replication; IDA:UniProt. DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0046105; P:thymidine biosynthetic process; IDA:UniProt. DR GO; GO:0046104; P:thymidine metabolic process; IDA:UniProtKB. DR DisProt; DP02006; -. DR Gene3D; 3.30.60.20; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR001267; Thymidine_kinase. DR InterPro; IPR020633; Thymidine_kinase_CS. DR PANTHER; PTHR11441; THYMIDINE KINASE; 1. DR PANTHER; PTHR11441:SF0; THYMIDINE KINASE, CYTOSOLIC; 1. DR Pfam; PF00265; TK; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00603; TK_CELLULAR_TYPE; 1. DR Genevisible; P04183; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Transferase; Ubl conjugation; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..234 FT /note="Thymidine kinase, cytosolic" FT /id="PRO_0000174948" FT MOTIF 203..205 FT /note="KEN box" FT /evidence="ECO:0000269|PubMed:14701726" FT ACT_SITE 98 FT /note="Proton acceptor" FT /evidence="ECO:0000255" FT BINDING 26..33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV, FT ECO:0007744|PDB:2WVJ" FT BINDING 58..60 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:22385435, FT ECO:0007744|PDB:1W4R, ECO:0007744|PDB:1XBT, FT ECO:0007744|PDB:2WVJ" FT BINDING 97..100 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:15733844, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:2WVJ" FT BINDING 128 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV, FT ECO:0007744|PDB:2WVJ" FT BINDING 153 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV, FT ECO:0007744|PDB:2WVJ" FT BINDING 156 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV, FT ECO:0007744|PDB:2WVJ" FT BINDING 172..176 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:22385435, FT ECO:0007744|PDB:1W4R, ECO:0007744|PDB:1XBT, FT ECO:0007744|PDB:2WVJ" FT BINDING 181 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV" FT BINDING 185 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV, FT ECO:0007744|PDB:2WVJ" FT BINDING 188 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:15611477, FT ECO:0000269|PubMed:15733844, ECO:0000269|PubMed:17407781, FT ECO:0000269|PubMed:22385435, ECO:0007744|PDB:1W4R, FT ECO:0007744|PDB:1XBT, ECO:0007744|PDB:2ORV, FT ECO:0007744|PDB:2WVJ" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:14697231, FT ECO:0000269|PubMed:9575153, ECO:0007744|PubMed:23186163" FT MOD_RES 231 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:20068231" FT MUTAGEN 13 FT /note="S->A: Loss of phosphorylation. Constant expression FT during cell cycle. No effect on ATP-induced FT tetramerization." FT /evidence="ECO:0000269|PubMed:14697231, FT ECO:0000269|PubMed:14701726, ECO:0000269|PubMed:9575153" FT MUTAGEN 13 FT /note="S->D: Perturbes ATP-induced tetramerization. FT Retaines the enzymatic function with decreased thymidine FT affinity and catalytic efficiency." FT /evidence="ECO:0000269|PubMed:14697231" FT MUTAGEN 28 FT /note="M->I,A: 300-fold higher KM for thymidine." FT /evidence="ECO:0000269|PubMed:22385435" FT MUTAGEN 124 FT /note="L->A: 30-fold higher KM for thymidine." FT /evidence="ECO:0000269|PubMed:22385435" FT MUTAGEN 163 FT /note="T->S: 50-fold higher KM for thymidine." FT /evidence="ECO:0000269|PubMed:22385435" FT MUTAGEN 194 FT /note="S->P: No effect on phosphorylation." FT /evidence="ECO:0000269|PubMed:9575153" FT MUTAGEN 203..205 FT /note="KEN->AAA: Resistant to degradation in the mitotic FT exit phase." FT /evidence="ECO:0000269|PubMed:14701726" FT MUTAGEN 203..204 FT /note="KE->AA: Resistant to degradation in the mitotic exit FT phase." FT /evidence="ECO:0000269|PubMed:14701726" FT MUTAGEN 203 FT /note="K->A: Resistant to degradation in the mitotic exit FT phase." FT /evidence="ECO:0000269|PubMed:14701726" FT CONFLICT 106 FT /note="V -> M (in Ref. 1; AAA61187 and 2; AAA61191)" FT /evidence="ECO:0000305" FT STRAND 20..26 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 32..45 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 50..55 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 61..63 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 67..72 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 73..80 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 81..84 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 85..89 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 92..98 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 99..101 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 105..114 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 118..126 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 144..148 FT /evidence="ECO:0007829|PDB:1W4R" FT TURN 154..156 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 162..167 FT /evidence="ECO:0007829|PDB:1W4R" FT TURN 178..180 FT /evidence="ECO:0007829|PDB:1W4R" FT STRAND 181..184 FT /evidence="ECO:0007829|PDB:1W4R" FT HELIX 186..189 FT /evidence="ECO:0007829|PDB:1W4R" SQ SEQUENCE 234 AA; 25469 MW; 76901415C631EF21 CRC64; MSCINLPTVL PGSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQYKC LVIKYAKDTR YSSSFCTHDR NTMEALPACL LRDVAQEALG VAVIGIDEGQ FFPDIVEFCE AMANAGKTVI VAALDGTFQR KPFGAILNLV PLAESVVKLT AVCMECFREA AYTKRLGTEK EVEVIGGADK YHSVCRLCYF KKASGQPAGP DNKENCPVPG KPGEAVAARK LFAPQQILQC SPAN //