KITH_HUMAN
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 03-AUG-2022, entry version 215.
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: BOLA2B; 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}.
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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; 225.
DR IntAct; P04183; 177.
DR MINT; P04183; -.
DR STRING; 9606.ENSP00000301634; -.
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; P04183; -.
DR PeptideAtlas; P04183; -.
DR PRIDE; P04183; -.
DR ProteomicsDB; 51674; -.
DR ABCD; P04183; 2 sequenced antibodies.
DR Antibodypedia; 3322; 469 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 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; GWLELIC; -.
DR PhylomeDB; P04183; -.
DR TreeFam; TF314839; -.
DR BioCyc; MetaCyc:HS09657-MON; -.
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; 25 hits in 1085 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 125 other tissues.
DR ExpressionAtlas; P04183; baseline and differential.
DR Genevisible; P04183; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
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:0046104; P:thymidine metabolic process; IDA:UniProtKB.
DR DisProt; DP02006; -.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001267; Thymidine_kinase.
DR InterPro; IPR020633; Thymidine_kinase_CS.
DR PANTHER; PTHR11441; PTHR11441; 1.
DR Pfam; PF00265; TK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00603; TK_CELLULAR_TYPE; 1.
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
