KITH_MOUSE
ID KITH_MOUSE Reviewed; 233 AA.
AC P04184; Q58EU0; Q8C3P8; Q921J8;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Thymidine kinase, cytosolic;
DE EC=2.7.1.21 {ECO:0000250|UniProtKB:P04183};
GN Name=Tk1; Synonyms=Tk-1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=3018504; DOI=10.1128/mcb.5.11.3149-3156.1985;
RA Lin P.-F., Lieberman H.B., Yeh D.-B., Xu T., Zhao S.-Y., Ruddle F.H.;
RT "Molecular cloning and structural analysis of murine thymidine kinase
RT genomic and cDNA sequences.";
RL Mol. Cell. Biol. 5:3149-3156(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=1496920; DOI=10.1016/0065-2571(92)90020-z;
RA Wintersberger E., Rotheneder H., Grabner M., Beck G., Seiser C.;
RT "Regulation of thymidine kinase during growth, cell cycle and
RT differentiation.";
RL Adv. Enzyme Regul. 32:241-254(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-88.
RX PubMed=1511894; DOI=10.1016/0378-1119(92)90190-z;
RA Gudas J.M., Fridovich-Keil J.L., Datta M.W., Bryan J., Pardee A.B.;
RT "Characterization of the murine thymidine kinase-encoding gene and analysis
RT of transcription start point heterogeneity.";
RL Gene 118:205-216(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7681542; DOI=10.1016/0027-5107(93)90195-l;
RA Liechty M.C., Rauchfuss H.S., Lugo M.H., Hozier J.C.;
RT "Sequence analysis of tka(-)-1 and tkb(+)-1 alleles in L5178Y tk+/-mouse-
RT lymphoma cells and spontaneous tk-/-mutants.";
RL Mutat. Res. 286:299-307(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Cerebellum, Stomach, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N, and NMRI; TISSUE=Mammary tumor;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-32.
RC TISSUE=Liver;
RX PubMed=1762910; DOI=10.1093/nar/19.24.6805;
RA Rotheneder H., Grabner M., Wintersberger E.;
RT "Presence of regulatory sequences within intron 2 of the mouse thymidine
RT kinase gene.";
RL Nucleic Acids Res. 19:6805-6809(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
RX PubMed=3244356; DOI=10.1128/mcb.8.12.5280-5291.1988;
RA Lieberman H.B., Lin P.F., Yeh D.B., Ruddle F.H.;
RT "Transcriptional and posttranscriptional mechanisms regulate murine
RT thymidine kinase gene expression in serum-stimulated cells.";
RL Mol. Cell. Biol. 8:5280-5291(1988).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Cell-cycle-regulated enzyme of importance in nucleotide
CC metabolism. Catalyzes the first enzymatic step in the salvage pathway
CC converting thymidine into thymidine monophosphate. Transcriptional
CC regulation limits expression to the S phase of the cell cycle and
CC transient expression coincides with the oscillation in the
CC intracellular dTTP concentration. {ECO:0000250|UniProtKB:P04183}.
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:0000250|UniProtKB:P04183};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19130;
CC Evidence={ECO:0000250|UniProtKB:P04183};
CC -!- SUBUNIT: Homotetramer. Tetramerization from dimerization is induced by
CC ATP and increases catalytic efficiency due to a high affinity for
CC thymidine. Tetramerization is inhibited by phosphorylation at Ser-13.
CC Interacts (via the KEN box) with FZR1. {ECO:0000250|UniProtKB:P04183}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P04184-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04184-2; Sequence=VSP_061491;
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:0000250|UniProtKB:P04183}.
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. {ECO:0000250|UniProtKB:P04183}.
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:0000250|UniProtKB:P04183}.
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; M11945; AAA40451.1; -; mRNA.
DR EMBL; M19438; AAA40452.1; -; mRNA.
DR EMBL; M68489; AAA40454.1; -; Genomic_DNA.
DR EMBL; S57244; AAB26001.1; -; mRNA.
DR EMBL; AK085188; BAC39384.1; -; mRNA.
DR EMBL; AK087988; BAC40077.1; -; mRNA.
DR EMBL; AK139244; BAE23931.1; -; mRNA.
DR EMBL; BC012215; AAH12215.1; -; mRNA.
DR EMBL; BC091758; AAH91758.1; -; mRNA.
DR EMBL; X60980; CAA43296.1; -; Genomic_DNA.
DR EMBL; M22581; AAA40450.1; -; Genomic_DNA.
DR CCDS; CCDS25692.1; -. [P04184-1]
DR PIR; JC1252; KIMST.
DR RefSeq; NP_001258658.1; NM_001271729.1.
DR RefSeq; NP_033413.2; NM_009387.2.
DR AlphaFoldDB; P04184; -.
DR SMR; P04184; -.
DR BioGRID; 204212; 1.
DR STRING; 10090.ENSMUSP00000026661; -.
DR BindingDB; P04184; -.
DR ChEMBL; CHEMBL2618; -.
DR iPTMnet; P04184; -.
DR PhosphoSitePlus; P04184; -.
DR EPD; P04184; -.
DR jPOST; P04184; -.
DR MaxQB; P04184; -.
DR PaxDb; P04184; -.
DR PeptideAtlas; P04184; -.
DR PRIDE; P04184; -.
DR ProteomicsDB; 263610; -.
DR Antibodypedia; 3322; 469 antibodies from 40 providers.
DR DNASU; 21877; -.
DR Ensembl; ENSMUST00000026661; ENSMUSP00000026661; ENSMUSG00000025574. [P04184-1]
DR GeneID; 21877; -.
DR KEGG; mmu:21877; -.
DR UCSC; uc007mnz.2; mouse. [P04184-1]
DR CTD; 7083; -.
DR MGI; MGI:98763; Tk1.
DR VEuPathDB; HostDB:ENSMUSG00000025574; -.
DR eggNOG; KOG3125; Eukaryota.
DR GeneTree; ENSGT00390000011309; -.
DR HOGENOM; CLU_064400_3_1_1; -.
DR InParanoid; P04184; -.
DR OMA; GWLELIC; -.
DR OrthoDB; 1413914at2759; -.
DR PhylomeDB; P04184; -.
DR TreeFam; TF314839; -.
DR BRENDA; 2.7.1.21; 3474.
DR Reactome; R-MMU-73614; Pyrimidine salvage.
DR SABIO-RK; P04184; -.
DR BioGRID-ORCS; 21877; 16 hits in 73 CRISPR screens.
DR ChiTaRS; Tk1; mouse.
DR PRO; PR:P04184; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P04184; protein.
DR Bgee; ENSMUSG00000025574; Expressed in fetal liver hematopoietic progenitor cell and 183 other tissues.
DR Genevisible; P04184; MM.
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; ISO:MGI.
DR GO; GO:0004797; F:thymidine kinase activity; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0046104; P:thymidine metabolic process; ISS:UniProtKB.
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 Acetylation; Alternative splicing; ATP-binding; Cytoplasm; DNA synthesis;
KW Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT CHAIN 2..233
FT /note="Thymidine kinase, cytosolic"
FT /id="PRO_0000174949"
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:0000305"
FT BINDING 58..60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 97..100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 172..176
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT BINDING 188
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04183"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform 2)"
FT /id="VSP_061491"
FT VARIANT 88
FT /note="S -> A"
FT /evidence="ECO:0000269|PubMed:1511894"
FT CONFLICT 27
FT /note="P -> L (in Ref. 6; AAH91758)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="S -> L (in Ref. 1; AAA40451/AAA40452)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="C -> G (in Ref. 5; BAC39384)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="A -> V (in Ref. 5; BAC39384)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 233 AA; 25776 MW; 78366623EDED0C6C CRC64;
MSYINLPTVL PSSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQYKC LVIKYAKDTR
YSNSFSTHDR NTMDALPACM LRDVTQESLG VAVIGIDEGQ FFPDIVDFCE MMANEGKTVI
VAALDGTFQR KAFGSILNLV PLAESVVKLT AVCMECFREA AYTKRLGLEK EVEVIGGADK
YHSVCRLCYF KKSSAQTAGS DNKNCLVLGQ PGEALVVRKL FASQQVLQYN SAN
