ID   KITM_MOUSE              Reviewed;         270 AA.
AC   Q9R088;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2001, sequence version 2.
DT   27-MAR-2024, entry version 132.
DE   RecName: Full=Thymidine kinase 2, mitochondrial {ECO:0000305};
DE            EC=2.7.1.21 {ECO:0000269|PubMed:11023833};
DE   AltName: Full=2'-deoxyuridine kinase TK2 {ECO:0000305};
DE            EC=2.7.1.74 {ECO:0000269|PubMed:11023833};
DE   AltName: Full=Deoxycytidine kinase TK2 {ECO:0000305};
DE            EC=2.7.1.- {ECO:0000269|PubMed:11023833};
DE   AltName: Full=Mt-TK;
DE   Flags: Precursor;
GN   Name=Tk2;
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], AND SUBCELLULAR LOCATION.
RX   PubMed=10571069; DOI=10.1016/s0014-5793(99)01325-3;
RA   Wettin K., Johansson M., Zheng X., Zhu C., Karlsson A.;
RT   "Cloning of mouse mitochondrial thymidine kinase 2 cDNA.";
RL   FEBS Lett. 460:103-106(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=11023833; DOI=10.1042/bj3510469;
RA   Wang L., Eriksson S.;
RT   "Cloning and characterization of full length mouse thymidine kinase 2: the
RT   N -terminal sequence directs import of the precursor protein into
RT   mitochondria.";
RL   Biochem. J. 351:469-476(2000).
CC   -!- FUNCTION: Phosphorylates thymidine, deoxycytidine, and deoxyuridine in
CC       the mitochondrial matrix (PubMed:11023833). In non-replicating cells,
CC       where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis
CC       depends solely on TK2 and DGUOK (By similarity).
CC       {ECO:0000250|UniProtKB:O00142, ECO:0000269|PubMed:11023833}.
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:11023833};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19130;
CC         Evidence={ECO:0000269|PubMed:11023833};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2'-deoxycytidine + ATP = ADP + dCMP + H(+);
CC         Xref=Rhea:RHEA:46040, ChEBI:CHEBI:15378, ChEBI:CHEBI:15698,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:57566, ChEBI:CHEBI:456216;
CC         EC=2.7.1.74; Evidence={ECO:0000269|PubMed:11023833};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46041;
CC         Evidence={ECO:0000269|PubMed:11023833};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2'-deoxyuridine + ATP = ADP + dUMP + H(+);
CC         Xref=Rhea:RHEA:28206, ChEBI:CHEBI:15378, ChEBI:CHEBI:16450,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:246422, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000269|PubMed:11023833};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28207;
CC         Evidence={ECO:0000269|PubMed:11023833};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3.4 uM for thymidine {ECO:0000269|PubMed:11023833};
CC         KM=25.1 uM for deoxycytidine {ECO:0000269|PubMed:11023833};
CC         Vmax=64 nmol/min/mg enzyme with thymidine as substrate
CC         {ECO:0000269|PubMed:11023833};
CC         Vmax=270 nmol/min/mg enzyme with deoxycytidine as substrate
CC         {ECO:0000269|PubMed:11023833};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11023833}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10571069,
CC       ECO:0000269|PubMed:11023833}.
CC   -!- TISSUE SPECIFICITY: Found in most tissues; highly expressed in liver.
CC       {ECO:0000269|PubMed:11023833}.
CC   -!- SIMILARITY: Belongs to the DCK/DGK family. {ECO:0000305}.
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DR   EMBL; AF105217; AAF08104.1; -; mRNA.
DR   EMBL; AJ249341; CAC07190.2; -; mRNA.
DR   CCDS; CCDS22573.1; -.
DR   AlphaFoldDB; Q9R088; -.
DR   SMR; Q9R088; -.
DR   STRING; 10090.ENSMUSP00000053616; -.
DR   PhosphoSitePlus; Q9R088; -.
DR   MaxQB; Q9R088; -.
DR   PaxDb; 10090-ENSMUSP00000053616; -.
DR   ProteomicsDB; 263552; -.
DR   Pumba; Q9R088; -.
DR   AGR; MGI:1913266; -.
DR   MGI; MGI:1913266; Tk2.
DR   eggNOG; KOG4235; Eukaryota.
DR   InParanoid; Q9R088; -.
DR   PhylomeDB; Q9R088; -.
DR   BRENDA; 2.7.1.21; 3474.
DR   Reactome; R-MMU-73614; Pyrimidine salvage.
DR   SABIO-RK; Q9R088; -.
DR   PRO; PR:Q9R088; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q9R088; Protein.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004137; F:deoxycytidine kinase activity; IDA:UniProtKB.
DR   GO; GO:0019136; F:deoxynucleoside kinase activity; IBA:GO_Central.
DR   GO; GO:0004797; F:thymidine kinase activity; IDA:UniProtKB.
DR   GO; GO:0046092; P:deoxycytidine metabolic process; ISO:MGI.
DR   GO; GO:0009262; P:deoxyribonucleotide metabolic process; IMP:MGI.
DR   GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0032042; P:mitochondrial DNA metabolic process; IMP:MGI.
DR   GO; GO:0006264; P:mitochondrial DNA replication; IMP:MGI.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0046104; P:thymidine metabolic process; ISO:MGI.
DR   CDD; cd01673; dNK; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR002624; DCK/DGK.
DR   InterPro; IPR031314; DNK_dom.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   PANTHER; PTHR10513; DEOXYNUCLEOSIDE KINASE; 1.
DR   PANTHER; PTHR10513:SF35; THYMIDINE KINASE 2, MITOCHONDRIAL; 1.
DR   Pfam; PF01712; dNK; 1.
DR   PIRSF; PIRSF000705; DNK; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; DNA synthesis; Kinase; Mitochondrion; Nucleotide-binding;
KW   Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..38
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           39..270
FT                   /note="Thymidine kinase 2, mitochondrial"
FT                   /id="PRO_0000016844"
FT   REGION          1..54
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        138
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:O57203"
FT   BINDING         62..70
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O57203"
FT   CONFLICT        14
FT                   /note="P -> L (in Ref. 1; AAF08104)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        23
FT                   /note="G -> R (in Ref. 1; AAF08104)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        155
FT                   /note="G -> S (in Ref. 1; AAF08104)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        269..270
FT                   /note="GP -> WTLGLSDLQDSARNSPARARCHGPRA (in Ref. 1;
FT                   AAF08104)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   270 AA;  31209 MW;  886F5B80D2C3EFE2 CRC64;
     MLLRSLRSWA ARSPRSVGPG SSGSPGSLDS GAGPLWAPRR AWPPDKDREN DKEKKAVVCI
     EGNIASGKTT CLEFFSNTTD VEVLMEPVLK WRNVHGHNPL SLMYHDASRW GLTLQTYVQL
     TMLDQHTRPQ MSPVRLMERS IYSARYIFVE NLYRGGKMPE VDYAILSEWF DWIVRNIDVS
     VDLIVYLRTT PEICYQRLKM RCREEEKVIP MEYLHAIHRL YEEWLVNGSL FPAAAPVLVI
     EADHNLEKML ELFEQNRARI LTPENWKHGP
//