TK
Protein
Thymidine kinase
Gene
TK
Organism
Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed-Annotation score: -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
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.
Catalytic activityi
- ATP + thymidine = ADP + dTMP + H+UniRule annotation
EC:2.7.1.21UniRule annotation
Source: Rhea. « HideATP
+thymidine">zoom
=ADP+dTMP+H+
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Active sitei | 83 | Proton acceptorUniRule annotation | 1 | |
| Binding sitei | 101 | SubstrateUniRule annotation | 1 | |
| Binding sitei | 125 | SubstrateUniRule annotation | 1 | |
| Binding sitei | 216 | ATPUniRule annotation | 1 | |
| Binding sitei | 222 | SubstrateUniRule annotation | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 56 – 63 | ATPUniRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-UniRule
- thymidine kinase activity Source: UniProtKB-UniRule
GO - Biological processi
- DNA biosynthetic process Source: UniProtKB-UniRule
- TMP biosynthetic process Source: UniProtKB-UniRule
Keywordsi
| Molecular function | Kinase, Transferase |
| Biological process | DNA synthesis |
| Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
| BRENDAi | 2.7.1.21, 2647 |
| SABIO-RKi | Q9QNF7 |
Names & Taxonomyi
| Protein namesi |
Recommended name:
Thymidine kinaseUniRule annotation (EC:2.7.1.21UniRule annotation) |
| Gene namesi |
Name:TKUniRule annotation
Synonyms:UL23 |
| Organismi | Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1) |
| Taxonomic identifieri | 10298 [NCBI] |
| Taxonomic lineagei | Viruses › Duplodnaviria › Heunggongvirae › Peploviricota › Herviviricetes › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus |
| Virus hosti | Homo 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
| ChEMBLi | CHEMBL1795127 |
| DrugBanki | DB00787, Acyclovir DB00249, Idoxuridine DB00577, Valaciclovir DB00194, Vidarabine |
| DrugCentrali | Q9QNF7 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000175068 | 1 – 376 | Thymidine kinaseAdd BLAST | 376 |
Interactioni
Subunit structurei
Homodimer.
UniRule annotation
Protein-protein interaction databases
| IntActi | Q9QNF7, 3 interactors |
| MINTi | Q9QNF7 |
Chemistry databases
| BindingDBi | Q9QNF7 |
Family & Domainsi
Sequence similaritiesi
Belongs to the herpesviridae thymidine kinase family.UniRule annotation
Family and domain databases
| HAMAPi | MF_04029, HSV_KITH, 1 hit |
| InterProi | View protein in InterPro IPR001889, Herpes_TK IPR027417, P-loop_NTPase |
| Pfami | View protein in Pfam PF00693, Herpes_TK, 1 hit |
| SUPFAMi | SSF52540, SSF52540, 1 hit |
Sequencei
Sequence statusi: Complete.
Q9QNF7-1 [UniParc]FASTAAdd to basket
« Hide
10 20 30 40 50MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL 60 70 80 90 100RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI 110 120 130 140 150YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS 160 170 180 190 200HAPPPALTLI FDRHPIAALL CYPAARYLMG SMTPQAVLAF VALIPPTLPG 210 220 230 240 250TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG LLANTVRYLQ 260 270 280 290 300GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 310 320 330 340 350NGDLYNVFAW 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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural varianti | 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. | 1 | |
| Natural varianti | 17 | A → V in strain: Isolate clinical CH/1. | 1 | |
| Natural varianti | 23 | S → N in strain: Isolate clinical h3. | 1 | |
| Natural varianti | 29 | L → V in strain: Isolate clinical h17. | 1 | |
| Natural varianti | 41 | R → H in strain: Isolate clinical h4. | 1 | |
| Natural varianti | 42 | L → P in strain: Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical CH/1. | 1 | |
| Natural varianti | 51 | R → W in strain: Isolate clinical HE/2; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 55 | D → N in strain: Isolate CL17; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 65 | T → N in strain: Isolate CL18; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 83 | E → K in strain: Isolate clinical LA/2; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 84 | P → S in strain: Isolate CL19; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 85 | M → I in strain: Isolate clinical VA/1. | 1 | |
| Natural varianti | 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. | 1 | |
| Natural varianti | 105 | H → P in strain: Isolate clinical CH/1; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 158 | T → A in strain: Isolate clinical h20. | 1 | |
| Natural varianti | 158 | T → I in strain: Isolate clinical h13. | 1 | |
| Natural varianti | 173 | P → R in strain: Isolate CL20; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 175 | A → V in strain: Isolate clinical BR/2; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 191 | V → L in strain: Isolate clinical h3. | 1 | |
| Natural varianti | 192 | A → V in strain: Isolate clinical LA/1 and Isolate clinical LA/2; acyclovir resistant. | 1 | |
| Natural varianti | 200 | G → C in strain: Isolate CL21; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 212 | R → K in strain: Isolate clinical h5. | 1 | |
| Natural varianti | 240 | G → E in strain: Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1 and Isolate clinical VA/1. | 1 | |
| Natural varianti | 243 | A → V in strain: Isolate clinical h5. | 1 | |
| Natural varianti | 245 | T → M in strain: Isolate CL22; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 251 | G → A in strain: Isolate clinical h25. | 1 | |
| Natural varianti | 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. | 1 | |
| Natural varianti | 257 | E → Q in strain: Isolate clinical h25. | 1 | |
| Natural varianti | 267 | V → L in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2 and Isolate clinical MA/1. | 1 | |
| Natural varianti | 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. | 1 | |
| Natural varianti | 271 | G → V in strain: Isolate clinical h12. | 1 | |
| Natural varianti | 279 | G → D in strain: Isolate clinical h11, Isolate clinical h12. | 1 | |
| Natural varianti | 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. | 1 | |
| Natural varianti | 287 | T → M in strain: Isolate CL23; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 316 | A → V in strain: Isolate clinical h15. | 1 | |
| Natural varianti | 317 | K → R in strain: Isolate clinical h4. | 1 | |
| Natural varianti | 332 | S → A in strain: Isolate clinical h17. | 1 | |
| Natural varianti | 336 | C → Y in strain: Isolate CL24; acyclovir resistant. 1 Publication | 1 | |
| Natural varianti | 348 | V → I in strain: Isolate clinical h20. | 1 | |
| Natural varianti | 355 | P → Q in strain: Isolate clinical h23 and Isolate clinical h24. | 1 | |
| Natural varianti | 364 | L → P in strain: Isolate clinical BR/2. | 1 | |
| Natural varianti | 374 | E → A in strain: Isolate clinical CH/1. | 1 | |
| Natural varianti | 376 | N → 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 |
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 |
Similar proteinsi
- 100% Identity
- 90% Identity
- 50% Identity
| Protein | Similar proteins | Species | Score | Length | Source | |
|---|---|---|---|---|---|---|
| Q9QNF7 | Thymidine kinase | 376 | UniRef100_Q9QNF7 | |||
| Thymidine kinase | 331 | |||||
| Thymidine kinase (Fragment) | 352 | |||||
| Thymidine kinase | 331 |
Cross-referencesi
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi |
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
| SMRi | Q9QNF7 |
| ModBasei | Search... |
Protein-protein interaction databases
| IntActi | Q9QNF7, 3 interactors |
| MINTi | Q9QNF7 |
Chemistry databases
| BindingDBi | Q9QNF7 |
| ChEMBLi | CHEMBL1795127 |
| DrugBanki | DB00787, Acyclovir DB00249, Idoxuridine DB00577, Valaciclovir DB00194, Vidarabine |
| DrugCentrali | Q9QNF7 |
Enzyme and pathway databases
| BRENDAi | 2.7.1.21, 2647 |
| SABIO-RKi | Q9QNF7 |
Family and domain databases
| HAMAPi | MF_04029, HSV_KITH, 1 hit |
| InterProi | View protein in InterPro IPR001889, Herpes_TK IPR027417, P-loop_NTPase |
| Pfami | View protein in Pfam PF00693, Herpes_TK, 1 hit |
| SUPFAMi | SSF52540, SSF52540, 1 hit |
| ProtoNeti | Search... |
| MobiDBi | Search... |
Entry informationi
| Entry namei | KITH_HHV1 | |
| Accessioni | Primary (citable) accession number: Q9QNF7 Secondary accession number(s): Q9ENR2 Q9IZ09 |
|
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 2005 |
| Last sequence update: | May 1, 2000 | |
| Last modified: | December 2, 2020 | |
| This is version 72 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Viral Protein Annotation Program | |
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