ID   KITH_HHV1C              Reviewed;         376 AA.
AC   P06478;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   24-JAN-2024, entry version 95.
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=UL23;
OS   Human herpesvirus 1 (strain CL101) (HHV-1) (Human herpes simplex virus 1).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus;
OC   Simplexvirus humanalpha1; Human herpesvirus 1.
OX   NCBI_TaxID=10302;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6262799; DOI=10.1073/pnas.78.3.1441;
RA   Wagner M.J., Sharp J.A., Summers W.C.;
RT   "Nucleotide sequence of the thymidine kinase gene of herpes simplex virus
RT   type 1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:1441-1445(1981).
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; J02224; AAA45811.1; -; Genomic_DNA.
DR   EMBL; V00467; CAA23741.1; -; Genomic_DNA.
DR   PIR; A93870; KIBETC.
DR   SMR; P06478; -.
DR   DrugBank; DB00299; Penciclovir.
DR   DrugBank; DB00577; Valaciclovir.
DR   SABIO-RK; P06478; -.
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; P-loop containing nucleotide triphosphate hydrolases; 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; P-loop containing nucleoside triphosphate hydrolases; 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_0000175070"
FT   REGION          1..39
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        83
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         101
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT   BINDING         125
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT   BINDING         216
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT   BINDING         222
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
SQ   SEQUENCE   376 AA;  40913 MW;  FFBAF5DC0B13D151 CRC64;
     MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL RVYIDGPHGM
     GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI YTTQHRLDQG EISAGDAAVV
     MTSAQITMGM PYAVTDAVLA PHVGGEAGSS HAPPPALTLI FDRHPIAALL CYPAARYLMG
     SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG
     LLANTVRYLQ GGGSWWEDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
     NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT HVTTPGSIPT
     ICDLARTFAR EMGEAN
//