ID   KITH_HHV1S              Reviewed;         376 AA.
AC   P06479;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   24-JAN-2024, entry version 82.
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 SC16) (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=10309;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3007662; DOI=10.1099/0022-1317-67-4-753;
RA   Darby G., Larder B.A., Inglis M.M.;
RT   "Evidence that the 'active centre' of the herpes simplex virus thymidine
RT   kinase involves an interaction between three distinct regions of the
RT   polypeptide.";
RL   J. Gen. Virol. 67:753-758(1986).
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; X03764; CAA27395.1; -; Genomic_DNA.
DR   PIR; A27240; KIBE16.
DR   SMR; P06479; -.
DR   BindingDB; P06479; -.
DR   ChEMBL; CHEMBL1820; -.
DR   DrugCentral; P06479; -.
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_0000175073"
FT   REGION          1..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          260..280
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;  40877 MW;  5B661B145585125A CRC64;
     MASYPGHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RPEQKMPTLL RVYIDGPHGM
     GKTTTTQLLV ALGSRDDIVY VPEPMTYWRV LGASETIANI YTTQHRLDQG EISAGDAAVV
     MTSAQITMGM PYAVTDAVLA PHIGGEAGSS HAPPPALTLI FDRHPIAALL CYPAARYLMG
     SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG
     LLANTVRYLQ GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
     NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMIQT HVTTPGSIPT
     ICDLARTFAR EMGEAN
//