KITM_MOUSE
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 03-AUG-2022, entry version 127.
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; Q9R088; -.
DR PRIDE; Q9R088; -.
DR ProteomicsDB; 263552; -.
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; -; 1.
DR InterPro; IPR002624; DCK/DGK.
DR InterPro; IPR031314; DNK_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01712; dNK; 1.
DR PIRSF; PIRSF000705; DNK; 1.
DR SUPFAM; SSF52540; SSF52540; 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
