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Thymidine kinase (EC 2.7.1.21)

 KITH_HHV1               Reviewed;         376 AA.
Q9QNF7; Q9ENR2; Q9ENR3; Q9ENR4; Q9ENR5; Q9ENR6; Q9ENR7; Q9ENR8;
Q9ENR9; Q9ICF2; Q9ICF3; Q9ICH1; Q9IR31; Q9IR32; Q9IR33; Q9IR34;
Q9IR35; Q9IR36; Q9IR37; Q9IR38; Q9IR39; Q9IR40; Q9IYZ6; Q9IZ00;
Q9IZ01; Q9IZ04; Q9IZ05; Q9IZ06; Q9IZ08; Q9IZ09;
01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
12-APR-2017, entry version 62.
RecName: Full=Thymidine kinase {ECO:0000255|HAMAP-Rule:MF_04029};
EC=2.7.1.21 {ECO:0000255|HAMAP-Rule:MF_04029};
Name=TK {ECO:0000255|HAMAP-Rule:MF_04029}; Synonyms=UL23;
Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1).
Viruses; dsDNA viruses, no RNA stage; Herpesvirales; Herpesviridae;
Alphaherpesvirinae; Simplexvirus.
NCBI_TaxID=10298;
NCBI_TaxID=9606; Homo sapiens (Human).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ACYCLOVIR RESISTANT
TRP-51; LYS-83; PRO-105 AND VAL-175.
STRAIN=Isolate clinical BR/1, Isolate clinical BR/2,
Isolate clinical CH/1, Isolate clinical HE/1, Isolate clinical HE/2,
Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1,
Isolate clinical MO/1, Isolate clinical PR/1, Isolate clinical PR/2,
and Isolate clinical VA/1;
PubMed=10882609; DOI=10.1086/315696;
Morfin F., Souillet G., Bilger K., Ooka T., Aymard M., Thouvenot D.;
"Genetic characterization of thymidine kinase from acyclovir-resistant
and -susceptible herpes simplex virus type 1 isolated from bone marrow
transplant recipients.";
J. Infect. Dis. 182:290-293(2000).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=Isolate clinical h1, Isolate clinical h10,
Isolate clinical h11, Isolate clinical h12, Isolate clinical h13,
Isolate clinical h14, Isolate clinical h15, Isolate clinical h16,
Isolate clinical h17, Isolate clinical h18, Isolate clinical h19,
Isolate clinical h2, Isolate clinical h20, Isolate clinical h21,
Isolate clinical h22, Isolate clinical h23, Isolate clinical h24,
Isolate clinical h25, Isolate clinical h3, Isolate clinical h4,
Isolate clinical h5, Isolate clinical h6, Isolate clinical h7,
Isolate clinical h8, and Isolate clinical h9;
PubMed=10878078;
Nagamine M., Suzutani T., Saijo M., Hayashi K., Azuma M.;
"Comparison of polymorphism of thymidine kinase gene and restriction
fragment length polymorphism of genomic DNA in herpes simplex virus
type 1.";
J. Clin. Microbiol. 38:2750-2752(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ACYCLOVIR RESISTANT
ASN-55; ASN-65; SER-84; ARG-173; CYS-200; MET-245; MET-287 AND
TYR-336.
STRAIN=Isolate CL17, Isolate CL18, Isolate CL19, Isolate CL20,
Isolate CL21, Isolate CL22, Isolate CL23, Isolate CL24, and TAS;
PubMed=12406508; DOI=10.1016/S0166-3542(02)00131-6;
Saijo M., Suzutani T., De Clercq E., Niikura M., Maeda A.,
Morikawa S., Kurane I.;
"Genotypic and phenotypic characterization of the thymidine kinase of
ACV-resistant HSV-1 derived from an acyclovir-sensitive herpes simplex
virus type 1 strain.";
Antiviral Res. 56:253-262(2002).
-!- FUNCTION: Catalyzes the transfer of the gamma-phospho group of ATP
to thymidine to generate dTMP in the salvage pathway of pyrimidine
synthesis. The dTMP serves as a substrate for DNA polymerase
during viral DNA replication. Allows the virus to be reactivated
and to grow in non-proliferative cells lacking a high
concentration of phosphorylated nucleic acid precursors.
{ECO:0000255|HAMAP-Rule:MF_04029}.
-!- CATALYTIC ACTIVITY: ATP + thymidine = ADP + thymidine 5'-
phosphate. {ECO:0000255|HAMAP-Rule:MF_04029}.
-!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04029}.
-!- BIOTECHNOLOGY: Used in molecular biology as a selectable marker to
identify transfected eukaryotic cells. Used in cancer suicide gene
therapy to selectively kill transformed cells.
-!- MISCELLANEOUS: Phosphorylates and thereby activates certain drugs
used to treat herpes simplex infections like acyclovir (ACV),
valaciclovir, and famciclovir to a toxic form, that leads to
successful suppression of the infection, while the uninfected cell
does not have this ability because it lacks TK. Mutations in
thymidine kinase may induce HHV resistance to antiviral therapies
in immunocompromised patients. The most frequently observed
resistant strains are unable to express TK and are avirulent in
animal models of disease. Resistance may be acquired less
frequently by selecting variants which no longer recognize ACV or
ACV triphosphate as substrates but which retain normal functions.
-!- MISCELLANEOUS: The sequence shown is that of strain TAS.
-!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
{ECO:0000255|HAMAP-Rule:MF_04029}.
-----------------------------------------------------------------------
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EMBL; AF243477; AAF72491.1; -; Genomic_DNA.
EMBL; AF243478; AAF72492.1; -; Genomic_DNA.
EMBL; AF243479; AAF72493.1; -; Genomic_DNA.
EMBL; AF243481; AAF72495.1; -; Genomic_DNA.
EMBL; AF243482; AAF72496.1; -; Genomic_DNA.
EMBL; AF243483; AAF72497.1; -; Genomic_DNA.
EMBL; AF243486; AAF72500.1; -; Genomic_DNA.
EMBL; AF243487; AAF72501.1; -; Genomic_DNA.
EMBL; AF243488; AAF72502.1; -; Genomic_DNA.
EMBL; AF243492; AAF72506.1; -; Genomic_DNA.
EMBL; AF243493; AAF72507.1; -; Genomic_DNA.
EMBL; AF243494; AAF72508.1; -; Genomic_DNA.
EMBL; AB009260; BAA83999.1; -; Genomic_DNA.
EMBL; AB032866; BAA93054.1; -; Genomic_DNA.
EMBL; AB032867; BAA93055.1; -; Genomic_DNA.
EMBL; AB032868; BAA93056.1; -; Genomic_DNA.
EMBL; AB032869; BAA93057.1; -; Genomic_DNA.
EMBL; AB032870; BAA93058.1; -; Genomic_DNA.
EMBL; AB032871; BAA93059.1; -; Genomic_DNA.
EMBL; AB032872; BAA93060.1; -; Genomic_DNA.
EMBL; AB032873; BAA93061.1; -; Genomic_DNA.
EMBL; AB032874; BAA93062.1; -; Genomic_DNA.
EMBL; AB032875; BAA93063.1; -; Genomic_DNA.
EMBL; AB032876; BAA93064.1; -; Genomic_DNA.
EMBL; AB032877; BAA93065.1; -; Genomic_DNA.
EMBL; AB032878; BAA93066.1; -; Genomic_DNA.
EMBL; AB032879; BAA93067.1; -; Genomic_DNA.
EMBL; AB032880; BAA93068.1; -; Genomic_DNA.
EMBL; AB032881; BAA93069.1; -; Genomic_DNA.
EMBL; AB032882; BAA93070.1; -; Genomic_DNA.
EMBL; AB032883; BAA93071.1; -; Genomic_DNA.
EMBL; AB032884; BAA93072.1; -; Genomic_DNA.
EMBL; AB032885; BAA93073.1; -; Genomic_DNA.
EMBL; AB032886; BAA93074.1; -; Genomic_DNA.
EMBL; AB032887; BAA93075.1; -; Genomic_DNA.
EMBL; AB032888; BAA93076.1; -; Genomic_DNA.
EMBL; AB032889; BAA93077.1; -; Genomic_DNA.
EMBL; AB032890; BAA93078.1; -; Genomic_DNA.
EMBL; AB047358; BAB11915.1; -; Genomic_DNA.
EMBL; AB047371; BAB11948.1; -; Genomic_DNA.
EMBL; AB047372; BAB11949.1; -; Genomic_DNA.
EMBL; AB047373; BAB11950.1; -; Genomic_DNA.
EMBL; AB047374; BAB11951.1; -; Genomic_DNA.
EMBL; AB047375; BAB11952.1; -; Genomic_DNA.
EMBL; AB047376; BAB11953.1; -; Genomic_DNA.
EMBL; AB047377; BAB11954.1; -; Genomic_DNA.
EMBL; AB047378; BAB11955.1; -; Genomic_DNA.
ProteinModelPortal; Q9QNF7; -.
SMR; Q9QNF7; -.
IntAct; Q9QNF7; 3.
BindingDB; Q9QNF7; -.
ChEMBL; CHEMBL1795127; -.
DrugBank; DB00249; Idoxuridine.
DrugBank; DB00577; Valaciclovir.
DrugBank; DB00194; Vidarabine.
BRENDA; 2.7.1.21; 2647.
SABIO-RK; Q9QNF7; -.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004797; F:thymidine kinase activity; IEA:UniProtKB-EC.
GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
GO; GO:0006230; P:TMP biosynthetic process; IEA:InterPro.
HAMAP; MF_04029; HSV_KITH; 1.
InterPro; IPR001889; Herpes_TK.
InterPro; IPR027417; P-loop_NTPase.
Pfam; PF00693; Herpes_TK; 1.
SUPFAM; SSF52540; SSF52540; 1.
1: Evidence at protein level;
ATP-binding; DNA synthesis; Early protein; Kinase; Nucleotide-binding;
Transferase.
CHAIN 1 376 Thymidine kinase.
/FTId=PRO_0000175068.
NP_BIND 56 63 ATP. {ECO:0000255|HAMAP-Rule:MF_04029}.
ACT_SITE 83 83 Proton acceptor. {ECO:0000255|HAMAP-
Rule:MF_04029}.
BINDING 101 101 Substrate. {ECO:0000255|HAMAP-
Rule:MF_04029}.
BINDING 125 125 Substrate. {ECO:0000255|HAMAP-
Rule:MF_04029}.
BINDING 216 216 ATP. {ECO:0000255|HAMAP-Rule:MF_04029}.
BINDING 222 222 Substrate. {ECO:0000255|HAMAP-
Rule:MF_04029}.
VARIANT 6 6 C -> G (in strain: Isolate clinical h21,
Isolate clinical h22, Isolate clinical
h23, Isolate clinical h24, Isolate
clinical h25, Isolate clinical LA/1,
Isolate clinical LA/2 and Isolate
clinical MA/1).
VARIANT 17 17 A -> V (in strain: Isolate clinical CH/
1).
VARIANT 23 23 S -> N (in strain: Isolate clinical h3).
VARIANT 29 29 L -> V (in strain: Isolate clinical h17).
VARIANT 41 41 R -> H (in strain: Isolate clinical h4).
VARIANT 42 42 L -> P (in strain: Isolate clinical h21,
Isolate clinical h22, Isolate clinical
h23, Isolate clinical h24, Isolate
clinical h25, Isolate clinical CH/1).
VARIANT 51 51 R -> W (in strain: Isolate clinical HE/2;
acyclovir resistant).
{ECO:0000269|PubMed:10882609}.
VARIANT 55 55 D -> N (in strain: Isolate CL17;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 65 65 T -> N (in strain: Isolate CL18;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 83 83 E -> K (in strain: Isolate clinical LA/2;
acyclovir resistant).
{ECO:0000269|PubMed:10882609}.
VARIANT 84 84 P -> S (in strain: Isolate CL19;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 85 85 M -> I (in strain: Isolate clinical VA/
1).
VARIANT 89 89 Q -> R (in strain: Isolate clinical CH/1,
Isolate clinical h20, Isolate clinical
h21, Isolate clinical h22, Isolate
clinical h23, Isolate clinical h24,
Isolate clinical h25, Isolate clinical
LA/1, Isolate clinical LA/2, Isolate
clinical MA/1, Isolate clinical PR/1 and
Isolate clinical PR/2).
VARIANT 105 105 H -> P (in strain: Isolate clinical CH/1;
acyclovir resistant).
{ECO:0000269|PubMed:10882609}.
VARIANT 158 158 T -> A (in strain: Isolate clinical h20).
VARIANT 158 158 T -> I (in strain: Isolate clinical h13).
VARIANT 173 173 P -> R (in strain: Isolate CL20;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 175 175 A -> V (in strain: Isolate clinical BR/2;
acyclovir resistant).
{ECO:0000269|PubMed:10882609}.
VARIANT 191 191 V -> L (in strain: Isolate clinical h3).
VARIANT 192 192 A -> V (in strain: Isolate clinical LA/1
and Isolate clinical LA/2; acyclovir
resistant).
VARIANT 200 200 G -> C (in strain: Isolate CL21;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 212 212 R -> K (in strain: Isolate clinical h5).
VARIANT 240 240 G -> E (in strain: Isolate clinical BR/1,
Isolate clinical BR/2, Isolate clinical
CH/1 and Isolate clinical VA/1).
VARIANT 243 243 A -> V (in strain: Isolate clinical h5).
VARIANT 245 245 T -> M (in strain: Isolate CL22;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 251 251 G -> A (in strain: Isolate clinical h25).
VARIANT 251 251 G -> C (in strain: Isolate clinical LA/1,
Isolate clinical LA/2, Isolate clinical
MA/1, Isolate clinical PR/1 and Isolate
clinical PR/2).
VARIANT 257 257 E -> Q (in strain: Isolate clinical h25).
VARIANT 267 267 V -> L (in strain: Isolate clinical CH/1,
Isolate clinical LA/1, Isolate clinical
LA/2 and Isolate clinical MA/1).
VARIANT 268 268 P -> T (in strain: Isolate clinical CH/1,
Isolate clinical LA/1, Isolate clinical
LA/2, Isolate clinical MA/1, Isolate
clinical PR/1 and Isolate clinical PR/2).
VARIANT 271 271 G -> V (in strain: Isolate clinical h12).
VARIANT 279 279 G -> D (in strain: Isolate clinical h11,
Isolate clinical h12).
VARIANT 286 286 D -> E (in strain: Isolate clinical CH/1,
Isolate clinical LA/1, Isolate clinical
LA/2, Isolate clinical MA/1, Isolate
clinical PR/1 and Isolate clinical PR/2).
VARIANT 287 287 T -> M (in strain: Isolate CL23;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 316 316 A -> V (in strain: Isolate clinical h15).
VARIANT 317 317 K -> R (in strain: Isolate clinical h4).
VARIANT 332 332 S -> A (in strain: Isolate clinical h17).
VARIANT 336 336 C -> Y (in strain: Isolate CL24;
acyclovir resistant).
{ECO:0000269|PubMed:12406508}.
VARIANT 348 348 V -> I (in strain: Isolate clinical h20).
VARIANT 355 355 P -> Q (in strain: Isolate clinical h23
and Isolate clinical h24).
VARIANT 364 364 L -> P (in strain: Isolate clinical BR/
2).
VARIANT 374 374 E -> A (in strain: Isolate clinical CH/
1).
VARIANT 376 376 N -> H (in strain: Isolate clinical MA/1,
Isolate clinical PR/1 and Isolate
clinical PR/2).
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


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