KITH_VZVO
ID KITH_VZVO Reviewed; 341 AA.
AC P0C0E6; O57298; P14344; Q4JQT9;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Thymidine kinase {ECO:0000255|HAMAP-Rule:MF_04029};
DE EC=2.7.1.21 {ECO:0000255|HAMAP-Rule:MF_04029};
GN Name=TK {ECO:0000255|HAMAP-Rule:MF_04029}; OrderedLocusNames=ORF36;
OS Varicella-zoster virus (strain Oka vaccine) (HHV-3) (Human herpesvirus 3).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Varicellovirus.
OX NCBI_TaxID=341980;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2844967; DOI=10.1099/0022-1317-69-10-2585;
RA Sawyer M.H., Inchauspe G., Biron K.K., Waters D.J., Straus S.E.,
RA Ostrove J.M.;
RT "Molecular analysis of the pyrimidine deoxyribonucleoside kinase gene of
RT wild-type and acyclovir-resistant strains of varicella-zoster virus.";
RL J. Gen. Virol. 69:2585-2593(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2852653; DOI=10.1159/000150060;
RA Mori H., Shiraki K., Kato T., Hayakawa Y., Yamanishi K., Takahashi M.;
RT "Molecular analysis of the thymidine kinase gene of thymidine kinase-
RT deficient mutants of varicella-zoster virus.";
RL Intervirology 29:301-310(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=9883, and YS;
RX PubMed=1848597; DOI=10.1099/0022-1317-72-3-623;
RA Lacey S.F., Suzutani T., Powell K.L., Purifoy D.J., Honess R.W.;
RT "Analysis of mutations in the thymidine kinase genes of drug-resistant
RT varicella-zoster virus populations using the polymerase chain reaction.";
RL J. Gen. Virol. 72:623-630(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate Human/Japan/P-Oka/1970, and
RC Oka varicella vaccine Biken (V-Oka-Biken);
RX PubMed=12388706; DOI=10.1128/jvi.76.22.11447-11459.2002;
RA Gomi Y., Sunamachi H., Mori Y., Nagaike K., Takahashi M., Yamanishi K.;
RT "Comparison of the complete DNA sequences of the Oka varicella vaccine and
RT its parental virus.";
RL J. Virol. 76:11447-11459(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Oka varicella vaccine VarilRix (V-Oka-GSK), and
RC Oka varicella vaccine Varivax V-Oka-Merk);
RX PubMed=18787000; DOI=10.1128/jvi.00777-08;
RA Tillieux S.L., Halsey W.S., Thomas E.S., Voycik J.J., Sathe G.M.,
RA Vassilev V.;
RT "Complete DNA sequences of two oka strain varicella-zoster virus genomes.";
RL J. Virol. 82:11023-11044(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH ADP AND
RP BROMOVINYL-DEOXYURIDINE-MONOPHOSPHATE.
RX PubMed=12686543; DOI=10.1074/jbc.m302025200;
RA Bird L.E., Ren J., Wright A., Leslie K.D., Degreve B., Balzarini J.,
RA Stammers D.K.;
RT "Crystal structure of varicella zoster virus thymidine kinase.";
RL J. Biol. Chem. 278:24680-24687(2003).
CC -!- FUNCTION: Catalyzes the transfer of the gamma-phospho group of ATP to
CC thymidine to generate dTMP in the salvage pathway of pyrimidine
CC synthesis. The dTMP serves as a substrate for DNA polymerase during
CC viral DNA replication. Allows the virus to be reactivated and to grow
CC in non-proliferative cells lacking a high concentration of
CC phosphorylated nucleic acid precursors. {ECO:0000255|HAMAP-
CC Rule:MF_04029}.
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:0000255|HAMAP-Rule:MF_04029};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04029}.
CC -!- MISCELLANEOUS: Phosphorylates and thereby activates certain drugs like
CC acyclovir (ACV), valacyclovir, and famciclovir to a toxic form, that
CC leads to successful suppression of the infection, while the uninfected
CC cell does not have this ability because it lacks TK. Mutations in
CC thymidine kinase may induce HSV resistance to antiviral therapies in
CC immunocompromised patients. The most frequently observed resistant
CC strains are unable to express TK and are avirulent in animal models of
CC disease. Resistance may be acquired less frequently by selecting
CC variants which no longer recognize ACV or ACV triphosphate as
CC substrates but which retain normal functions (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
CC {ECO:0000255|HAMAP-Rule:MF_04029}.
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DR EMBL; M36160; AAA45865.1; -; Genomic_DNA.
DR EMBL; AB009252; BAA23727.2; -; Genomic_DNA.
DR EMBL; AB009253; BAA23728.2; -; Genomic_DNA.
DR EMBL; AB097932; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB097933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DQ008354; AAY57648.1; -; Genomic_DNA.
DR EMBL; DQ008355; AAY57719.1; -; Genomic_DNA.
DR PIR; A28930; KIBEEL.
DR PDB; 1OSN; X-ray; 3.20 A; A/B/C/D=1-341.
DR PDBsum; 1OSN; -.
DR SMR; P0C0E6; -.
DR IntAct; P0C0E6; 3.
DR ChEMBL; CHEMBL3308966; -.
DR DrugBank; DB04438; Brivudine monophosphate.
DR EvolutionaryTrace; P0C0E6; -.
DR Proteomes; UP000002603; Genome.
DR Proteomes; UP000008504; Genome.
DR Proteomes; UP000008505; Genome.
DR Proteomes; UP000008506; Genome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004797; F:thymidine kinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006230; P:TMP biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_04029; HSV_KITH; 1.
DR InterPro; IPR001889; Herpes_TK.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00693; Herpes_TK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; DNA synthesis; Early protein; Kinase;
KW Nucleotide-binding; Transferase.
FT CHAIN 1..341
FT /note="Thymidine kinase"
FT /id="PRO_0000175087"
FT ACT_SITE 48
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 19..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 66
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 90
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 183
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT STRAND 10..23
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 27..34
FT /evidence="ECO:0007829|PDB:1OSN"
FT TURN 35..38
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:1OSN"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 61..73
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 79..92
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:1OSN"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 133..136
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 154..158
FT /evidence="ECO:0007829|PDB:1OSN"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 177..183
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 196..218
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 224..227
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 233..239
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 258..261
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 275..290
FT /evidence="ECO:0007829|PDB:1OSN"
FT STRAND 292..297
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:1OSN"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:1OSN"
FT HELIX 323..336
FT /evidence="ECO:0007829|PDB:1OSN"
SQ SEQUENCE 341 AA; 37843 MW; F38ACC39751C076A CRC64;
MSTDKTDVKM GVLRIYLDGA YGIGKTTAAE EFLHHFAITP NRILLIGEPL SYWRNLAGED
AICGIYGTQT RRLNGDVSPE DAQRLTAHFQ SLFCSPHAIM HAKISALMDT STSDLVQVNK
EPYKIMLSDR HPIASTICFP LSRYLVGDMS PAALPGLLFT LPAEPPGTNL VVCTVSLPSH
LSRVSKRARP GETVNLPFVM VLRNVYIMLI NTIIFLKTNN WHAGWNTLSF CNDVFKQKLQ
KSECIKLREV PGIEDTLFAV LKLPELCGEF GNILPLWAWG METLSNCLRS MSPFVLSLEQ
TPQHAAQELK TLLPQMTPAN MSSGAWNILK ELVNAVQDNT S
