KITH_VZVD
ID KITH_VZVD Reviewed; 341 AA.
AC P09250; O57298; P0C0E5; P0C0E7; P14341; P14342; P14343; P14344;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 89.
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 Dumas) (HHV-3) (Human herpesvirus 3).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Varicellovirus.
OX NCBI_TaxID=10338;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=3018124; DOI=10.1099/0022-1317-67-9-1759;
RA Davison A.J., Scott J.E.;
RT "The complete DNA sequence of varicella-zoster virus.";
RL J. Gen. Virol. 67:1759-1816(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Ellen, Isolate 101, Isolate 3-5-2/KB3, Isolate 40a2, Isolate 7-1-3,
RC isolate clinical GK, and ppIIa;
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).
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; X04370; CAA27919.1; -; Genomic_DNA.
DR PIR; A27341; KIBE36.
DR PIR; A28930; KIBEEL.
DR PIR; B28930; KIBE73.
DR PIR; E28930; KIBEGK.
DR SMR; P09250; -.
DR BindingDB; P09250; -.
DR ChEMBL; CHEMBL4784; -.
DR DrugBank; DB00194; Vidarabine.
DR DrugCentral; P09250; -.
DR PRIDE; P09250; -.
DR Proteomes; UP000002602; 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 3: Inferred from homology;
KW ATP-binding; DNA synthesis; Early protein; Kinase; Nucleotide-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..341
FT /note="Thymidine kinase"
FT /id="PRO_0000175084"
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 VARIANT 130
FT /note="R -> Q (in strain: Isolate 7-1-3)"
FT VARIANT 154
FT /note="L -> P (in strain: Isolate 40a2)"
FT VARIANT 288
FT /note="S -> L (in strain: Ellen, ppIIa, Isolate clinical
FT GK, Isolate 7-1-3, Isolate 101 and Isolate 3-5-2/KB3)"
FT VARIANT 319
FT /note="A -> V (in strain: Isolate clinical GK)"
SQ SEQUENCE 341 AA; 37817 MW; 1C95CC39750B0C07 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 METLSNCSRS MSPFVLSLEQ
TPQHAAQELK TLLPQMTPAN MSSGAWNILK ELVNAVQDNT S
