ID   KITH_VACCA              Reviewed;         177 AA.
AC   O57203; Q6J3E4;
DT   02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   03-AUG-2022, entry version 89.
DE   RecName: Full=Thymidine kinase;
DE            EC=2.7.1.21;
GN   Name=TK; OrderedLocusNames=MVA086R, ACAM3000_MVA_086; ORFNames=J2R;
OS   Vaccinia virus (strain Ankara) (VACV).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX   NCBI_TaxID=126794;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=9601507; DOI=10.1006/viro.1998.9123;
RA   Antoine G., Scheiflinger F., Dorner F., Falkner F.G.;
RT   "The complete genomic sequence of the modified vaccinia Ankara strain:
RT   comparison with other orthopoxviruses.";
RL   Virology 244:365-396(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Isolate Acambis 3000;
RA   Esposito J.J., Frace M., Sammons S.A., Olsen-Rasmussen M.S., Osborne J.,
RA   Khristova M., Wohlhueter R.M.;
RL   Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND TTP,
RP   FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ACTIVE SITE, AND DISULFIDE BONDS.
RX   PubMed=17062140; DOI=10.1186/1472-6807-6-22;
RA   El Omari K., Solaroli N., Karlsson A., Balzarini J., Stammers D.K.;
RT   "Structure of vaccinia virus thymidine kinase in complex with dTTP:
RT   insights for drug design.";
RL   BMC Struct. Biol. 6:22-22(2006).
CC   -!- FUNCTION: Phosphorylates thymidine and thymidine analogs, such as
CC       azidothymidine (AZT). Part of the salvage pathway for pyrimidine
CC       deoxyribonucleotide synthesis. {ECO:0000269|PubMed:17062140}.
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:17062140};
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; U94848; AAB96503.1; -; Genomic_DNA.
DR   EMBL; AY603355; AAT10484.1; -; Genomic_DNA.
DR   PIR; T37362; T37362.
DR   PDB; 2J87; X-ray; 3.10 A; A/B/C/D=1-177.
DR   PDBsum; 2J87; -.
DR   SMR; O57203; -.
DR   BRENDA; 2.7.1.21; 6591.
DR   EvolutionaryTrace; O57203; -.
DR   Proteomes; UP000159908; Genome.
DR   Proteomes; UP000172909; 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   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Disulfide bond; DNA synthesis; Kinase;
KW   Metal-binding; Nucleotide-binding; Transferase; Zinc.
FT   CHAIN           1..177
FT                   /note="Thymidine kinase"
FT                   /id="PRO_0000174937"
FT   ACT_SITE        83
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         11..18
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         113
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         138
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         141
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         157..161
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         170
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   BINDING         173
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   DISULFID        170
FT                   /note="Interchain (with C-173)"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   DISULFID        173
FT                   /note="Interchain (with C-170)"
FT                   /evidence="ECO:0000269|PubMed:17062140,
FT                   ECO:0007744|PDB:2J87"
FT   STRAND          5..10
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           17..29
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   TURN            30..32
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          35..40
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          56..58
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           66..69
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   TURN            70..72
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           73..75
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          77..82
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           84..86
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           90..99
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          103..107
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   TURN            119..121
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           122..126
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          129..133
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   TURN            139..141
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          143..145
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          147..153
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   TURN            163..165
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   STRAND          166..169
FT                   /evidence="ECO:0007829|PDB:2J87"
FT   HELIX           171..174
FT                   /evidence="ECO:0007829|PDB:2J87"
SQ   SEQUENCE   177 AA;  20028 MW;  57E19BCEBE6F3C54 CRC64;
     MNGGHIQLII GPMFSGKSTE LIRRVRRYQI AQYKCVTIKY SNDNRYGTGL WTHDKNNFEA
     LEATKLCDVL ESITDFSVIG IDEGQFFPDI VEFCERMANE GKIVIVAALD GTFQRKPFNN
     ILNLIPLSEM VVKLTAVCMK CFKEASFSKR LGEETEIEII GGNDMYQSVC RKCYVGS