KITH_HHV1
ID KITH_HHV1 Reviewed; 376 AA.
AC Q9QNF7; P03176; Q9ENR2; Q9ENR3; Q9ENR4; Q9ENR5; Q9ENR6; Q9ENR7; Q9ENR8;
AC Q9ENR9; Q9ICF2; Q9ICF3; Q9ICH1; Q9IR31; Q9IR32; Q9IR33; Q9IR34; Q9IR35;
AC Q9IR36; Q9IR37; Q9IR38; Q9IR39; Q9IR40; Q9IYZ6; Q9IZ00; Q9IZ01; Q9IZ04;
AC Q9IZ05; Q9IZ06; Q9IZ08; Q9IZ09;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 76.
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}; Synonyms=UL23;
OS Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10298;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate McKnight;
RX PubMed=6258156; DOI=10.1093/nar/8.24.5949;
RA McKnight S.L.;
RT "The nucleotide sequence and transcript map of the herpes simplex virus
RT thymidine kinase gene.";
RL Nucleic Acids Res. 8:5949-5964(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ACYCLOVIR RESISTANT TRP-51;
RP LYS-83; PRO-105 AND VAL-175.
RC STRAIN=Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1,
RC Isolate clinical HE/1, Isolate clinical HE/2, Isolate clinical LA/1,
RC Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical MO/1,
RC Isolate clinical PR/1, Isolate clinical PR/2, and Isolate clinical VA/1;
RX PubMed=10882609; DOI=10.1086/315696;
RA Morfin F., Souillet G., Bilger K., Ooka T., Aymard M., Thouvenot D.;
RT "Genetic characterization of thymidine kinase from acyclovir-resistant and
RT -susceptible herpes simplex virus type 1 isolated from bone marrow
RT transplant recipients.";
RL J. Infect. Dis. 182:290-293(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate clinical h1, Isolate clinical h10, Isolate clinical h11,
RC Isolate clinical h12, Isolate clinical h13, Isolate clinical h14,
RC Isolate clinical h15, Isolate clinical h16, Isolate clinical h17,
RC Isolate clinical h18, Isolate clinical h19, Isolate clinical h2,
RC Isolate clinical h20, Isolate clinical h21, Isolate clinical h22,
RC Isolate clinical h23, Isolate clinical h24, Isolate clinical h25,
RC Isolate clinical h3, Isolate clinical h4, Isolate clinical h5,
RC Isolate clinical h6, Isolate clinical h7, Isolate clinical h8, and
RC Isolate clinical h9;
RX PubMed=10878078; DOI=10.1128/jcm.38.7.2750-2752.2000;
RA Nagamine M., Suzutani T., Saijo M., Hayashi K., Azuma M.;
RT "Comparison of polymorphism of thymidine kinase gene and restriction
RT fragment length polymorphism of genomic DNA in herpes simplex virus type
RT 1.";
RL J. Clin. Microbiol. 38:2750-2752(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ACYCLOVIR RESISTANT ASN-55;
RP ASN-65; SER-84; ARG-173; CYS-200; MET-245; MET-287 AND TYR-336.
RC STRAIN=Isolate CL17, Isolate CL18, Isolate CL19, Isolate CL20,
RC Isolate CL21, Isolate CL22, Isolate CL23, Isolate CL24, and TAS;
RX PubMed=12406508; DOI=10.1016/s0166-3542(02)00131-6;
RA Saijo M., Suzutani T., De Clercq E., Niikura M., Maeda A., Morikawa S.,
RA Kurane I.;
RT "Genotypic and phenotypic characterization of the thymidine kinase of ACV-
RT resistant HSV-1 derived from an acyclovir-sensitive herpes simplex virus
RT type 1 strain.";
RL Antiviral Res. 56:253-262(2002).
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 used
CC to treat herpes simplex infections like acyclovir (ACV), valaciclovir,
CC and famciclovir to a toxic form, that leads to successful suppression
CC of the infection, while the uninfected cell does not have this ability
CC because it lacks TK. Mutations in thymidine kinase may induce HHV
CC resistance to antiviral therapies in immunocompromised patients. The
CC most frequently observed resistant strains are unable to express TK and
CC are avirulent in animal models of disease. Resistance may be acquired
CC less frequently by selecting variants which no longer recognize ACV or
CC ACV triphosphate as substrates but which retain normal functions.
CC -!- MISCELLANEOUS: The sequence shown is that of strain TAS.
CC -!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
CC {ECO:0000255|HAMAP-Rule:MF_04029}.
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DR EMBL; V00470; CAA23742.1; -; Genomic_DNA.
DR EMBL; AF243477; AAF72491.1; -; Genomic_DNA.
DR EMBL; AF243478; AAF72492.1; -; Genomic_DNA.
DR EMBL; AF243479; AAF72493.1; -; Genomic_DNA.
DR EMBL; AF243481; AAF72495.1; -; Genomic_DNA.
DR EMBL; AF243482; AAF72496.1; -; Genomic_DNA.
DR EMBL; AF243483; AAF72497.1; -; Genomic_DNA.
DR EMBL; AF243486; AAF72500.1; -; Genomic_DNA.
DR EMBL; AF243487; AAF72501.1; -; Genomic_DNA.
DR EMBL; AF243488; AAF72502.1; -; Genomic_DNA.
DR EMBL; AF243492; AAF72506.1; -; Genomic_DNA.
DR EMBL; AF243493; AAF72507.1; -; Genomic_DNA.
DR EMBL; AF243494; AAF72508.1; -; Genomic_DNA.
DR EMBL; AB009260; BAA83999.1; -; Genomic_DNA.
DR EMBL; AB032866; BAA93054.1; -; Genomic_DNA.
DR EMBL; AB032867; BAA93055.1; -; Genomic_DNA.
DR EMBL; AB032868; BAA93056.1; -; Genomic_DNA.
DR EMBL; AB032869; BAA93057.1; -; Genomic_DNA.
DR EMBL; AB032870; BAA93058.1; -; Genomic_DNA.
DR EMBL; AB032871; BAA93059.1; -; Genomic_DNA.
DR EMBL; AB032872; BAA93060.1; -; Genomic_DNA.
DR EMBL; AB032873; BAA93061.1; -; Genomic_DNA.
DR EMBL; AB032874; BAA93062.1; -; Genomic_DNA.
DR EMBL; AB032875; BAA93063.1; -; Genomic_DNA.
DR EMBL; AB032876; BAA93064.1; -; Genomic_DNA.
DR EMBL; AB032877; BAA93065.1; -; Genomic_DNA.
DR EMBL; AB032878; BAA93066.1; -; Genomic_DNA.
DR EMBL; AB032879; BAA93067.1; -; Genomic_DNA.
DR EMBL; AB032880; BAA93068.1; -; Genomic_DNA.
DR EMBL; AB032881; BAA93069.1; -; Genomic_DNA.
DR EMBL; AB032882; BAA93070.1; -; Genomic_DNA.
DR EMBL; AB032883; BAA93071.1; -; Genomic_DNA.
DR EMBL; AB032884; BAA93072.1; -; Genomic_DNA.
DR EMBL; AB032885; BAA93073.1; -; Genomic_DNA.
DR EMBL; AB032886; BAA93074.1; -; Genomic_DNA.
DR EMBL; AB032887; BAA93075.1; -; Genomic_DNA.
DR EMBL; AB032888; BAA93076.1; -; Genomic_DNA.
DR EMBL; AB032889; BAA93077.1; -; Genomic_DNA.
DR EMBL; AB032890; BAA93078.1; -; Genomic_DNA.
DR EMBL; AB047358; BAB11915.1; -; Genomic_DNA.
DR EMBL; AB047371; BAB11948.1; -; Genomic_DNA.
DR EMBL; AB047372; BAB11949.1; -; Genomic_DNA.
DR EMBL; AB047373; BAB11950.1; -; Genomic_DNA.
DR EMBL; AB047374; BAB11951.1; -; Genomic_DNA.
DR EMBL; AB047375; BAB11952.1; -; Genomic_DNA.
DR EMBL; AB047376; BAB11953.1; -; Genomic_DNA.
DR EMBL; AB047377; BAB11954.1; -; Genomic_DNA.
DR EMBL; AB047378; BAB11955.1; -; Genomic_DNA.
DR SMR; Q9QNF7; -.
DR IntAct; Q9QNF7; 3.
DR MINT; Q9QNF7; -.
DR BindingDB; Q9QNF7; -.
DR ChEMBL; CHEMBL1795127; -.
DR DrugBank; DB00787; Acyclovir.
DR DrugBank; DB00249; Idoxuridine.
DR DrugBank; DB00577; Valaciclovir.
DR DrugBank; DB00194; Vidarabine.
DR DrugCentral; Q9QNF7; -.
DR BRENDA; 2.7.1.21; 2647.
DR SABIO-RK; Q9QNF7; -.
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_0000175068"
FT REGION 1..39
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"
FT VARIANT 6
FT /note="C -> G (in strain: Isolate McKnight, Isolate
FT clinical h21, Isolate clinical h22, Isolate clinical h23,
FT Isolate clinical h24, Isolate clinical h25, Isolate
FT clinical LA/1, Isolate clinical LA/2 and Isolate clinical
FT MA/1)"
FT VARIANT 17
FT /note="A -> V (in strain: Isolate clinical CH/1)"
FT VARIANT 23
FT /note="S -> N (in strain: Isolate clinical h3)"
FT VARIANT 29
FT /note="L -> V (in strain: Isolate clinical h17)"
FT VARIANT 41
FT /note="R -> H (in strain: Isolate clinical h4)"
FT VARIANT 42
FT /note="L -> P (in strain: Isolate McKnight, Isolate
FT clinical h21, Isolate clinical h22, Isolate clinical h23,
FT Isolate clinical h24, Isolate clinical h25, Isolate
FT clinical CH/1)"
FT VARIANT 51
FT /note="R -> W (in strain: Isolate clinical HE/2; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:10882609"
FT VARIANT 55
FT /note="D -> N (in strain: Isolate CL17; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 65
FT /note="T -> N (in strain: Isolate CL18; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 83
FT /note="E -> K (in strain: Isolate clinical LA/2; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:10882609"
FT VARIANT 84
FT /note="P -> S (in strain: Isolate CL19; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 85
FT /note="M -> I (in strain: Isolate clinical VA/1)"
FT VARIANT 89
FT /note="Q -> R (in strain: Isolate McKnight, Isolate
FT clinical CH/1, Isolate clinical h20, Isolate clinical h21,
FT Isolate clinical h22, Isolate clinical h23, Isolate
FT clinical h24, Isolate clinical h25, Isolate clinical LA/1,
FT Isolate clinical LA/2, Isolate clinical MA/1, Isolate
FT clinical PR/1 and Isolate clinical PR/2)"
FT VARIANT 105
FT /note="H -> P (in strain: Isolate clinical CH/1; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:10882609"
FT VARIANT 158
FT /note="T -> A (in strain: Isolate clinical h20)"
FT VARIANT 158
FT /note="T -> I (in strain: Isolate clinical h13)"
FT VARIANT 173
FT /note="P -> R (in strain: Isolate CL20; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 175
FT /note="A -> V (in strain: Isolate clinical BR/2; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:10882609"
FT VARIANT 191
FT /note="V -> L (in strain: Isolate clinical h3)"
FT VARIANT 192
FT /note="A -> V (in strain: Isolate clinical LA/1 and Isolate
FT clinical LA/2; acyclovir resistant)"
FT VARIANT 200
FT /note="G -> C (in strain: Isolate CL21; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 212
FT /note="R -> K (in strain: Isolate clinical h5)"
FT VARIANT 240
FT /note="G -> E (in strain: Isolate clinical BR/1, Isolate
FT clinical BR/2, Isolate clinical CH/1 and Isolate clinical
FT VA/1)"
FT VARIANT 243
FT /note="A -> V (in strain: Isolate clinical h5)"
FT VARIANT 245
FT /note="T -> M (in strain: Isolate CL22; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 251
FT /note="G -> A (in strain: Isolate clinical h25)"
FT VARIANT 251
FT /note="G -> C (in strain: Isolate McKnight, Isolate
FT clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/
FT 1, Isolate clinical PR/1 and Isolate clinical PR/2)"
FT VARIANT 257
FT /note="E -> Q (in strain: Isolate clinical h25)"
FT VARIANT 267
FT /note="V -> L (in strain: Isolate clinical CH/1, Isolate
FT clinical LA/1, Isolate clinical LA/2 and Isolate clinical
FT MA/1)"
FT VARIANT 268
FT /note="P -> T (in strain: Isolate clinical CH/1, Isolate
FT clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/
FT 1, Isolate clinical PR/1 and Isolate clinical PR/2)"
FT VARIANT 271
FT /note="G -> V (in strain: Isolate clinical h12)"
FT VARIANT 279
FT /note="G -> D (in strain: Isolate clinical h11, Isolate
FT clinical h12)"
FT VARIANT 286
FT /note="D -> E (in strain: Isolate clinical CH/1, Isolate
FT clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/
FT 1, Isolate clinical PR/1 and Isolate clinical PR/2)"
FT VARIANT 287
FT /note="T -> M (in strain: Isolate CL23; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 316
FT /note="A -> V (in strain: Isolate clinical h15)"
FT VARIANT 317
FT /note="K -> R (in strain: Isolate clinical h4)"
FT VARIANT 321
FT /note="P -> S (in strain: Isolate McKnight)"
FT VARIANT 332
FT /note="S -> A (in strain: Isolate clinical h17)"
FT VARIANT 336
FT /note="C -> Y (in strain: Isolate CL24; acyclovir
FT resistant)"
FT /evidence="ECO:0000269|PubMed:12406508"
FT VARIANT 348
FT /note="V -> I (in strain: Isolate clinical h20)"
FT VARIANT 355
FT /note="P -> Q (in strain: Isolate clinical h23 and Isolate
FT clinical h24)"
FT VARIANT 364
FT /note="L -> P (in strain: Isolate clinical BR/2)"
FT VARIANT 374
FT /note="E -> A (in strain: Isolate clinical CH/1)"
FT VARIANT 376
FT /note="N -> H (in strain: Isolate clinical MA/1, Isolate
FT clinical PR/1 and Isolate clinical PR/2)"
SQ SEQUENCE 376 AA; 40897 MW; 86A177947F9AB1C7 CRC64;
MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL RVYIDGPHGM
GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV 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 LQLTSGMVQT HVTTPGSIPT
ICDLARTFAR EMGEAN
