ID   KITH_VAR67              Reviewed;         177 AA.
AC   P0DOM7; P04364; Q9QNJ1;
DT   16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT   16-OCT-2019, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Thymidine kinase;
DE            EC=2.7.1.21;
GN   Name=TK; ORFNames=J2R, L2R, M2R;
OS   Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX   NCBI_TaxID=587200;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8383392; DOI=10.1016/0168-1702(93)90110-9;
RA   Shchelkunov S.N., Blinov V.M., Totmenin A.V., Marennikova S.S.,
RA   Kolykhalov A.A., Frolov I.V., Chizhikov V.E., Gytorov V.V., Gashikov P.V.,
RA   Belanov E.F., Belavin P.A., Resenchuk S.M., Andzhaparidze O.G.,
RA   Sandakhchiev L.S.;
RT   "Nucleotide sequence analysis of variola virus HindIII M, L, I genome
RT   fragments.";
RL   Virus Res. 27:25-35(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=8384129; DOI=10.1016/0014-5793(93)80041-r;
RA   Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S.;
RT   "Genes of variola and vaccinia viruses necessary to overcome the host
RT   protective mechanisms.";
RL   FEBS Lett. 319:80-83(1993).
CC   -!- FUNCTION: Phosphorylates thymidine and thymidine analogs, such as
CC       azidothymidine (AZT). Part of the salvage pathway for pyrimidine
CC       deoxyribonucleotide synthesis (By similarity). {ECO:0000250}.
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   -!- SUBUNIT: Homotetramer. Two molecules of substrate bind to each enzyme
CC       tetramer. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the thymidine kinase family. {ECO:0000305}.
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DR   EMBL; X67119; CAA47578.1; -; Genomic_DNA.
DR   EMBL; X69198; CAA49020.1; -; Genomic_DNA.
DR   EMBL; S55844; AAB24675.1; -; Genomic_DNA.
DR   PIR; A00611; KIVZVV.
DR   RefSeq; NP_042123.1; NC_001611.1.
DR   SMR; P0DOM7; -.
DR   GeneID; 1486465; -.
DR   KEGG; vg:1486465; -.
DR   Proteomes; UP000002060; Genome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004797; F:thymidine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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   PIRSF; PIRSF035805; TK_cell; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   PROSITE; PS00603; TK_CELLULAR_TYPE; 1.
PE   3: Inferred from homology;
KW   ATP-binding; DNA synthesis; Kinase; Metal-binding; Nucleotide-binding;
KW   Reference proteome; Transferase; Zinc.
FT   CHAIN           1..177
FT                   /note="Thymidine kinase"
FT                   /id="PRO_0000174941"
FT   ACT_SITE        83
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255"
FT   BINDING         11..18
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         113
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         138
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         141
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         157..161
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         170
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         173
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   177 AA;  20055 MW;  580FF33308BE5A35 CRC64;
     MNGGHIQLII GPMFSGKSTE LIRRVRRYQI AQYKCVTIKY SNDNRYGTGL WTHDKNNFEA
     LEATKLCDVL EAITDFSVIG IDEGQFFPDI VEFCERMANE GKIVIVAALD GTFQRKPFNN
     ILDLIPLSEM VVKLTAVCMK CFKEASFSKR LGTETKIEII GGIDMYQSVC RKCYIDS