ID   KTHY_VACCC              Reviewed;         204 AA.
AC   P68693; P13410;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   07-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 64.
DE   RecName: Full=Thymidylate kinase;
DE            EC=2.7.4.9;
DE   AltName: Full=dTMP kinase;
GN   Name=TMK; ORFNames=A48R;
OS   Vaccinia virus (strain Copenhagen) (VACV).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX   NCBI_TaxID=10249;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=2219722; DOI=10.1016/0042-6822(90)90294-2;
RA   Goebel S.J., Johnson G.P., Perkus M.E., Davis S.W., Winslow J.P.,
RA   Paoletti E.;
RT   "The complete DNA sequence of vaccinia virus.";
RL   Virology 179:247-266(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Goebel S.J., Johnson G.P., Perkus M.E., Davis S.W., Winslow J.P.,
RA   Paoletti E.;
RT   "Appendix to 'The complete DNA sequence of vaccinia virus'.";
RL   Virology 179:517-563(1990).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX   PubMed=18971333; DOI=10.1073/pnas.0804525105;
RA   Caillat C., Topalis D., Agrofoglio L.A., Pochet S., Balzarini J.,
RA   Deville-Bonne D., Meyer P.;
RT   "Crystal structure of poxvirus thymidylate kinase: an unexpected
RT   dimerization has implications for antiviral therapy.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:16900-16905(2008).
CC   -!- FUNCTION: Poxvirus TMP kinase is able to phosphorylate dTMP, dUMP and
CC       also dGMP from any purine and pyrimidine nucleoside triphosphate. The
CC       large substrate specificity is explained by the presence of a canal
CC       connecting the edge of the dimer interface to the TMP base binding
CC       pocket, canal not found in the human homolog (By similarity).
CC       {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + dTMP = ADP + dTDP; Xref=Rhea:RHEA:13517,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:58369, ChEBI:CHEBI:63528,
CC         ChEBI:CHEBI:456216; EC=2.7.4.9;
CC   -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC   -!- SUBUNIT: Homodimer; the dimer arrangement is orthogonal and not
CC       antiparallel as in human enzyme. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the thymidylate kinase family. {ECO:0000305}.
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DR   EMBL; M35027; AAA48180.1; -; Genomic_DNA.
DR   PIR; E42522; KIVZ5W.
DR   PDB; 2V54; X-ray; 2.40 A; A/B=1-204.
DR   PDB; 2W0S; X-ray; 2.92 A; A/B=1-204.
DR   PDBsum; 2V54; -.
DR   PDBsum; 2W0S; -.
DR   SMR; P68693; -.
DR   DIP; DIP-48617N; -.
DR   BRENDA; 2.7.4.9; 6591.
DR   UniPathway; UPA00575; -.
DR   EvolutionaryTrace; P68693; -.
DR   Proteomes; UP000008269; Genome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004798; F:thymidylate kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006233; P:dTDP biosynthetic process; IEA:InterPro.
DR   GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR039430; Thymidylate_kin-like_dom.
DR   InterPro; IPR018095; Thymidylate_kin_CS.
DR   InterPro; IPR018094; Thymidylate_kinase.
DR   Pfam; PF02223; Thymidylate_kin; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   TIGRFAMs; TIGR00041; DTMP_kinase; 1.
DR   PROSITE; PS01331; THYMIDYLATE_KINASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Kinase; Nucleotide biosynthesis;
KW   Nucleotide-binding; Reference proteome; Transferase.
FT   CHAIN           1..204
FT                   /note="Thymidylate kinase"
FT                   /id="PRO_0000155217"
FT   BINDING         11..18
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305"
FT   STRAND          6..10
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           17..26
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           30..32
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   STRAND          33..39
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           44..53
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           61..73
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           76..84
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   STRAND          88..93
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           95..104
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           109..116
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   STRAND          119..121
FT                   /evidence="ECO:0007829|PDB:2W0S"
FT   STRAND          123..128
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           132..135
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   STRAND          140..142
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           148..161
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   STRAND          168..171
FT                   /evidence="ECO:0007829|PDB:2V54"
FT   HELIX           177..194
FT                   /evidence="ECO:0007829|PDB:2V54"
SQ   SEQUENCE   204 AA;  23219 MW;  911DFD2C671CF6B3 CRC64;
     MSRGALIVFE GLDKSGKTTQ CMNIMESIPA NTIKYLNFPQ RSTVTGKMID DYLTRKKTYN
     DHIVNLLFCA NRWEFASFIQ EQLEQGITLI VDRYAFSGVA YAAAKGASMT LSKSYESGLP
     KPDLVIFLES GSKEINRNVG EEIYEDVTFQ QKVLQEYKKM IEEGDIHWQI ISSEFEEDVK
     KELIKNIVIE AIHTVTGPVG QLWM