ID   KITH_VARV               Reviewed;         177 AA.
AC   P0DOM8; P04364; Q9QNJ1;
DT   16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT   16-OCT-2019, sequence version 1.
DT   03-AUG-2022, entry version 11.
DE   RecName: Full=Thymidine kinase;
DE            EC=2.7.1.21;
GN   Name=TK; ORFNames=J2R, L2R, M2R;
OS   Variola virus.
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX   NCBI_TaxID=10255;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Bangladesh-1975;
RX   PubMed=6330986; DOI=10.1016/0042-6822(84)90212-5;
RA   Esposito J.J., Knight J.C.;
RT   "Nucleotide sequence of the thymidine kinase gene region of monkeypox and
RT   variola viruses.";
RL   Virology 135:561-567(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Bangladesh-1975;
RX   PubMed=8264798; DOI=10.1038/366748a0;
RA   Massung R.F., Esposito J.J., Liu L.I., Qi J., Utterback T.R., Knight J.C.,
RA   Aubin L., Yuran T.E., Parsons J.M., Loparev V.N., Selivanov N.A.,
RA   Cavallaro K.F., Kerlavage A.R., Mahy B.W.J., Venter J.C.;
RT   "Potential virulence determinants in terminal regions of variola smallpox
RT   virus genome.";
RL   Nature 366:748-751(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Garcia-1966;
RX   PubMed=10639322; DOI=10.1006/viro.1999.0086;
RA   Shchelkunov S.N., Totmenin A.V., Loparev V.N., Safronov P.F., Gutorov V.V.,
RA   Chizhikov V.E., Knight J.C., Parsons J.M., Massung R.F., Esposito J.J.;
RT   "Alastrim smallpox variola minor virus genome DNA sequences.";
RL   Virology 266:361-386(2000).
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; K02031; AAA80461.1; -; Genomic_DNA.
DR   EMBL; S55844; AAB24675.1; -; Genomic_DNA.
DR   EMBL; L22579; AAA60827.1; -; Genomic_DNA.
DR   EMBL; Y16780; CAB54679.1; -; Genomic_DNA.
DR   PIR; E72160; E72160.
DR   PIR; T28517; T28517.
DR   SMR; P0DOM8; -.
DR   Proteomes; UP000111493; Genome.
DR   Proteomes; UP000119805; 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   Transferase; Zinc.
FT   CHAIN           1..177
FT                   /note="Thymidine kinase"
FT                   /id="PRO_0000448110"
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"
FT   VARIANT         90
FT                   /note="I -> V (in strain: Bangladesh-1975)"
FT   VARIANT         153
FT                   /note="A -> T (in strain: Bangladesh-1975)"
FT   VARIANT         163
FT                   /note="I -> N (in strain: Bangladesh-1975)"
SQ   SEQUENCE   177 AA;  20025 MW;  4C5EB63308BE5A35 CRC64;
     MNGGHIQLII GPMFSGKSTE LIRRVRRYQI AQYKCVTIKY SNDNRYGTGL WTHDKNNFEA
     LEATKLCDVL EAITDFSVIG IDEGQFFPDI VEFCERMANE GKIVIVAALD GTFQRKPFNN
     ILDLIPLSEM VVKLTAVCMK CFKEASFSKR LGAETKIEII GGIDMYQSVC RKCYIDS