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 04-NOV-2026, 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}; OS Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2). OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes; OC Herpesvirales; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus; OC Simplexvirus humanalpha2; Human herpesvirus 2. 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=thymidine + ATP = dTMP + ADP + 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 AlphaFoldDB; P04407; -. 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: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_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 //