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Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.UniRule annotation

Catalytic activityi

ATP + thymidine = ADP + thymidine 5'-phosphate.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei83Proton acceptorUniRule annotation1
Binding sitei101SubstrateUniRule annotation1
Binding sitei125SubstrateUniRule annotation1
Binding sitei216ATPUniRule annotation1
Binding sitei222SubstrateUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi56 – 63ATPUniRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

DNA synthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.21. 2647.
SABIO-RKQ9QNF7.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinaseUniRule annotation (EC:2.7.1.21UniRule annotation)
Gene namesi
Name:TKUniRule annotation
Synonyms:UL23
OrganismiHuman herpesvirus 1 (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10298 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Pathology & Biotechi

Biotechnological usei

Used in molecular biology as a selectable marker to identify transfected eukaryotic cells. Used in cancer suicide gene therapy to selectively kill transformed cells.

Chemistry databases

ChEMBLiCHEMBL1795127.
DrugBankiDB00249. Idoxuridine.
DB00577. Valaciclovir.
DB00194. Vidarabine.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001750681 – 376Thymidine kinaseAdd BLAST376

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.UniRule annotation

Protein-protein interaction databases

IntActiQ9QNF7. 3 interactors.

Chemistry databases

BindingDBiQ9QNF7.

Structurei

3D structure databases

ProteinModelPortaliQ9QNF7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the herpesviridae thymidine kinase family.UniRule annotation

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_04029. HSV_KITH. 1 hit.
InterProiIPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00693. Herpes_TK. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9QNF7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL
60 70 80 90 100
RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI
110 120 130 140 150
YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS
160 170 180 190 200
HAPPPALTLI FDRHPIAALL CYPAARYLMG SMTPQAVLAF VALIPPTLPG
210 220 230 240 250
TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG LLANTVRYLQ
260 270 280 290 300
GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
310 320 330 340 350
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT
360 370
HVTTPGSIPT ICDLARTFAR EMGEAN
Length:376
Mass (Da):40,897
Last modified:May 1, 2000 - v1
Checksum:i86A177947F9AB1C7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti6C → 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. 1
Natural varianti17A → V in strain: Isolate clinical CH/1. 1
Natural varianti23S → N in strain: Isolate clinical h3. 1
Natural varianti29L → V in strain: Isolate clinical h17. 1
Natural varianti41R → H in strain: Isolate clinical h4. 1
Natural varianti42L → P in strain: Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical CH/1. 1
Natural varianti51R → W in strain: Isolate clinical HE/2; acyclovir resistant. 1 Publication1
Natural varianti55D → N in strain: Isolate CL17; acyclovir resistant. 1 Publication1
Natural varianti65T → N in strain: Isolate CL18; acyclovir resistant. 1 Publication1
Natural varianti83E → K in strain: Isolate clinical LA/2; acyclovir resistant. 1 Publication1
Natural varianti84P → S in strain: Isolate CL19; acyclovir resistant. 1 Publication1
Natural varianti85M → I in strain: Isolate clinical VA/1. 1
Natural varianti89Q → 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. 1
Natural varianti105H → P in strain: Isolate clinical CH/1; acyclovir resistant. 1 Publication1
Natural varianti158T → A in strain: Isolate clinical h20. 1
Natural varianti158T → I in strain: Isolate clinical h13. 1
Natural varianti173P → R in strain: Isolate CL20; acyclovir resistant. 1 Publication1
Natural varianti175A → V in strain: Isolate clinical BR/2; acyclovir resistant. 1 Publication1
Natural varianti191V → L in strain: Isolate clinical h3. 1
Natural varianti192A → V in strain: Isolate clinical LA/1 and Isolate clinical LA/2; acyclovir resistant. 1
Natural varianti200G → C in strain: Isolate CL21; acyclovir resistant. 1 Publication1
Natural varianti212R → K in strain: Isolate clinical h5. 1
Natural varianti240G → E in strain: Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1 and Isolate clinical VA/1. 1
Natural varianti243A → V in strain: Isolate clinical h5. 1
Natural varianti245T → M in strain: Isolate CL22; acyclovir resistant. 1 Publication1
Natural varianti251G → A in strain: Isolate clinical h25. 1
Natural varianti251G → C in strain: Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2. 1
Natural varianti257E → Q in strain: Isolate clinical h25. 1
Natural varianti267V → L in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2 and Isolate clinical MA/1. 1
Natural varianti268P → 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. 1
Natural varianti271G → V in strain: Isolate clinical h12. 1
Natural varianti279G → D in strain: Isolate clinical h11, Isolate clinical h12. 1
Natural varianti286D → 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. 1
Natural varianti287T → M in strain: Isolate CL23; acyclovir resistant. 1 Publication1
Natural varianti316A → V in strain: Isolate clinical h15. 1
Natural varianti317K → R in strain: Isolate clinical h4. 1
Natural varianti332S → A in strain: Isolate clinical h17. 1
Natural varianti336C → Y in strain: Isolate CL24; acyclovir resistant. 1 Publication1
Natural varianti348V → I in strain: Isolate clinical h20. 1
Natural varianti355P → Q in strain: Isolate clinical h23 and Isolate clinical h24. 1
Natural varianti364L → P in strain: Isolate clinical BR/2. 1
Natural varianti374E → A in strain: Isolate clinical CH/1. 1
Natural varianti376N → H in strain: Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF243477 Genomic DNA. Translation: AAF72491.1.
AF243478 Genomic DNA. Translation: AAF72492.1.
AF243479 Genomic DNA. Translation: AAF72493.1.
AF243481 Genomic DNA. Translation: AAF72495.1.
AF243482 Genomic DNA. Translation: AAF72496.1.
AF243483 Genomic DNA. Translation: AAF72497.1.
AF243486 Genomic DNA. Translation: AAF72500.1.
AF243487 Genomic DNA. Translation: AAF72501.1.
AF243488 Genomic DNA. Translation: AAF72502.1.
AF243492 Genomic DNA. Translation: AAF72506.1.
AF243493 Genomic DNA. Translation: AAF72507.1.
AF243494 Genomic DNA. Translation: AAF72508.1.
AB009260 Genomic DNA. Translation: BAA83999.1.
AB032866 Genomic DNA. Translation: BAA93054.1.
AB032867 Genomic DNA. Translation: BAA93055.1.
AB032868 Genomic DNA. Translation: BAA93056.1.
AB032869 Genomic DNA. Translation: BAA93057.1.
AB032870 Genomic DNA. Translation: BAA93058.1.
AB032871 Genomic DNA. Translation: BAA93059.1.
AB032872 Genomic DNA. Translation: BAA93060.1.
AB032873 Genomic DNA. Translation: BAA93061.1.
AB032874 Genomic DNA. Translation: BAA93062.1.
AB032875 Genomic DNA. Translation: BAA93063.1.
AB032876 Genomic DNA. Translation: BAA93064.1.
AB032877 Genomic DNA. Translation: BAA93065.1.
AB032878 Genomic DNA. Translation: BAA93066.1.
AB032879 Genomic DNA. Translation: BAA93067.1.
AB032880 Genomic DNA. Translation: BAA93068.1.
AB032881 Genomic DNA. Translation: BAA93069.1.
AB032882 Genomic DNA. Translation: BAA93070.1.
AB032883 Genomic DNA. Translation: BAA93071.1.
AB032884 Genomic DNA. Translation: BAA93072.1.
AB032885 Genomic DNA. Translation: BAA93073.1.
AB032886 Genomic DNA. Translation: BAA93074.1.
AB032887 Genomic DNA. Translation: BAA93075.1.
AB032888 Genomic DNA. Translation: BAA93076.1.
AB032889 Genomic DNA. Translation: BAA93077.1.
AB032890 Genomic DNA. Translation: BAA93078.1.
AB047358 Genomic DNA. Translation: BAB11915.1.
AB047371 Genomic DNA. Translation: BAB11948.1.
AB047372 Genomic DNA. Translation: BAB11949.1.
AB047373 Genomic DNA. Translation: BAB11950.1.
AB047374 Genomic DNA. Translation: BAB11951.1.
AB047375 Genomic DNA. Translation: BAB11952.1.
AB047376 Genomic DNA. Translation: BAB11953.1.
AB047377 Genomic DNA. Translation: BAB11954.1.
AB047378 Genomic DNA. Translation: BAB11955.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF243477 Genomic DNA. Translation: AAF72491.1.
AF243478 Genomic DNA. Translation: AAF72492.1.
AF243479 Genomic DNA. Translation: AAF72493.1.
AF243481 Genomic DNA. Translation: AAF72495.1.
AF243482 Genomic DNA. Translation: AAF72496.1.
AF243483 Genomic DNA. Translation: AAF72497.1.
AF243486 Genomic DNA. Translation: AAF72500.1.
AF243487 Genomic DNA. Translation: AAF72501.1.
AF243488 Genomic DNA. Translation: AAF72502.1.
AF243492 Genomic DNA. Translation: AAF72506.1.
AF243493 Genomic DNA. Translation: AAF72507.1.
AF243494 Genomic DNA. Translation: AAF72508.1.
AB009260 Genomic DNA. Translation: BAA83999.1.
AB032866 Genomic DNA. Translation: BAA93054.1.
AB032867 Genomic DNA. Translation: BAA93055.1.
AB032868 Genomic DNA. Translation: BAA93056.1.
AB032869 Genomic DNA. Translation: BAA93057.1.
AB032870 Genomic DNA. Translation: BAA93058.1.
AB032871 Genomic DNA. Translation: BAA93059.1.
AB032872 Genomic DNA. Translation: BAA93060.1.
AB032873 Genomic DNA. Translation: BAA93061.1.
AB032874 Genomic DNA. Translation: BAA93062.1.
AB032875 Genomic DNA. Translation: BAA93063.1.
AB032876 Genomic DNA. Translation: BAA93064.1.
AB032877 Genomic DNA. Translation: BAA93065.1.
AB032878 Genomic DNA. Translation: BAA93066.1.
AB032879 Genomic DNA. Translation: BAA93067.1.
AB032880 Genomic DNA. Translation: BAA93068.1.
AB032881 Genomic DNA. Translation: BAA93069.1.
AB032882 Genomic DNA. Translation: BAA93070.1.
AB032883 Genomic DNA. Translation: BAA93071.1.
AB032884 Genomic DNA. Translation: BAA93072.1.
AB032885 Genomic DNA. Translation: BAA93073.1.
AB032886 Genomic DNA. Translation: BAA93074.1.
AB032887 Genomic DNA. Translation: BAA93075.1.
AB032888 Genomic DNA. Translation: BAA93076.1.
AB032889 Genomic DNA. Translation: BAA93077.1.
AB032890 Genomic DNA. Translation: BAA93078.1.
AB047358 Genomic DNA. Translation: BAB11915.1.
AB047371 Genomic DNA. Translation: BAB11948.1.
AB047372 Genomic DNA. Translation: BAB11949.1.
AB047373 Genomic DNA. Translation: BAB11950.1.
AB047374 Genomic DNA. Translation: BAB11951.1.
AB047375 Genomic DNA. Translation: BAB11952.1.
AB047376 Genomic DNA. Translation: BAB11953.1.
AB047377 Genomic DNA. Translation: BAB11954.1.
AB047378 Genomic DNA. Translation: BAB11955.1.

3D structure databases

ProteinModelPortaliQ9QNF7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9QNF7. 3 interactors.

Chemistry databases

BindingDBiQ9QNF7.
ChEMBLiCHEMBL1795127.
DrugBankiDB00249. Idoxuridine.
DB00577. Valaciclovir.
DB00194. Vidarabine.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

BRENDAi2.7.1.21. 2647.
SABIO-RKQ9QNF7.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_04029. HSV_KITH. 1 hit.
InterProiIPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00693. Herpes_TK. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKITH_HHV1
AccessioniPrimary (citable) accession number: Q9QNF7
Secondary accession number(s): 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
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: May 1, 2000
Last modified: October 5, 2016
This is version 60 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.
The sequence shown is that of strain TAS.

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.