KITH_HHV23
ID KITH_HHV23 Reviewed; 376 AA.
AC P04407;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 85.
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};
OS Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10313;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6317035; DOI=10.1016/0167-4781(83)90056-8;
RA Kit S., Kit M., Qavi H., Trkula D., Otsuka H.;
RT "Nucleotide sequence of the herpes simplex virus type 2 (HSV-2) thymidine
RT kinase gene and predicted amino acid sequence of thymidine kinase
RT polypeptide and its comparison with the HSV-1 thymidine kinase gene.";
RL Biochim. Biophys. Acta 741:158-170(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6304336; DOI=10.1128/jvi.46.3.1045-1050.1983;
RA Swain M.A., Galloway D.A.;
RT "Nucleotide sequence of the herpes simplex virus type 2 thymidine kinase
RT gene.";
RL J. Virol. 46:1045-1050(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2829709; DOI=10.1128/aac.31.10.1483;
RA Kit S., Sheppard M., Ichimura H., Nusinoff-Lehrman S., Ellis M.N.,
RA Fyfe J.A., Otsuka H.;
RT "Nucleotide sequence changes in thymidine kinase gene of herpes simplex
RT virus type 2 clones from an isolate of a patient treated with acyclovir.";
RL Antimicrob. Agents Chemother. 31:1483-1490(1987).
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 -!- BIOTECHNOLOGY: Used in molecular biology as a selectable marker to
CC identify transfected eukaryotic cells. Used in cancer suicide gene
CC therapy to selectively kill transformed cells.
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.
CC -!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
CC {ECO:0000255|HAMAP-Rule:MF_04029}.
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DR EMBL; X01712; CAA25858.1; -; Genomic_DNA.
DR EMBL; V00466; CAA23740.1; -; Genomic_DNA.
DR EMBL; M29942; AAA45856.1; -; Genomic_DNA.
DR PIR; A90648; KIBET3.
DR SMR; P04407; -.
DR BindingDB; P04407; -.
DR DrugCentral; P04407; -.
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 ATP-binding; DNA synthesis; Early protein; Kinase; Nucleotide-binding;
KW Transferase.
FT CHAIN 1..376
FT /note="Thymidine kinase"
FT /id="PRO_0000175074"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 84
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 56..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 126
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 217
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 223
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT CONFLICT 271
FT /note="Missing (in Ref. 1; CAA25858)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 376 AA; 40467 MW; 0B1D68B0BBA3C8A5 CRC64;
MASHAGQQHA PAFGQAARAS GPTDGRAASR PSHRQGASEA RGDPELPTLL RVYIDGPHGV
GKTTTSAQLM EALGPRDNIV YVPEPMTYWQ VLGASETLTN IYNTQHRLDR GEISAGEAAV
VMTSAQITMS TPYAATDAVL APHIGGEAVG PQAPPPALTL VFDRHPIASL LCYPAARYLM
GSMTPQAVLA FVALMPPTAP GTNLVLGVLP EAEHADRLAR RQRPGERLDL AMLSAIRRVY
DLLANTVRYL QRGGRWREDW GRLTGVAAAT PRPDPEDGAG SLPRIEDTLF ALFRVPELLA
PNGDLYHIFA WVLDVLADRL LPMHLFVLDY DQSPVGCRDA LLRLTAGMIP TRVTTAGSIA
EIRDLARTFA REVGGV
