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Q9QNF7

- KITH_HHV1

UniProt

Q9QNF7 - KITH_HHV1

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Protein

Thymidine kinase

Gene

TK

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

Functioni

In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome.By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei83 – 831Proton acceptorSequence Analysis
Binding sitei101 – 1011SubstrateBy similarity
Binding sitei125 – 1251SubstrateBy similarity
Binding sitei172 – 1721SubstrateBy similarity
Binding sitei216 – 2161ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi56 – 638ATPBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. thymidine kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. DNA replication Source: UniProtKB-KW
  2. TMP biosynthetic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

DNA synthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKQ9QNF7.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinase (EC:2.7.1.21)
Gene namesi
Name:TK
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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 376376Thymidine kinasePRO_0000175068Add
BLAST

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

IntActiQ9QNF7. 3 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ9QNF7.
SMRiQ9QNF7. Positions 46-376.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Family and domain databases

Gene3Di3.40.50.300. 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61C → 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.
Natural varianti17 – 171A → V in strain: Isolate clinical CH/1.
Natural varianti23 – 231S → N in strain: Isolate clinical h3.
Natural varianti29 – 291L → V in strain: Isolate clinical h17.
Natural varianti41 – 411R → H in strain: Isolate clinical h4.
Natural varianti42 – 421L → P in strain: Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical CH/1.
Natural varianti51 – 511R → W in strain: Isolate clinical HE/2; acyclovir resistant. 1 Publication
Natural varianti55 – 551D → N in strain: Isolate CL17; acyclovir resistant. 1 Publication
Natural varianti65 – 651T → N in strain: Isolate CL18; acyclovir resistant. 1 Publication
Natural varianti83 – 831E → K in strain: Isolate clinical LA/2; acyclovir resistant. 1 Publication
Natural varianti84 – 841P → S in strain: Isolate CL19; acyclovir resistant. 1 Publication
Natural varianti85 – 851M → I in strain: Isolate clinical VA/1.
Natural varianti89 – 891Q → 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.
Natural varianti105 – 1051H → P in strain: Isolate clinical CH/1; acyclovir resistant. 1 Publication
Natural varianti158 – 1581T → A in strain: Isolate clinical h20.
Natural varianti158 – 1581T → I in strain: Isolate clinical h13.
Natural varianti173 – 1731P → R in strain: Isolate CL20; acyclovir resistant. 1 Publication
Natural varianti175 – 1751A → V in strain: Isolate clinical BR/2; acyclovir resistant. 1 Publication
Natural varianti191 – 1911V → L in strain: Isolate clinical h3.
Natural varianti192 – 1921A → V in strain: Isolate clinical LA/1 and Isolate clinical LA/2; acyclovir resistant.
Natural varianti200 – 2001G → C in strain: Isolate CL21; acyclovir resistant. 1 Publication
Natural varianti212 – 2121R → K in strain: Isolate clinical h5.
Natural varianti240 – 2401G → E in strain: Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1 and Isolate clinical VA/1.
Natural varianti243 – 2431A → V in strain: Isolate clinical h5.
Natural varianti245 – 2451T → M in strain: Isolate CL22; acyclovir resistant. 1 Publication
Natural varianti251 – 2511G → A in strain: Isolate clinical h25.
Natural varianti251 – 2511G → C in strain: Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.
Natural varianti257 – 2571E → Q in strain: Isolate clinical h25.
Natural varianti267 – 2671V → L in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2 and Isolate clinical MA/1.
Natural varianti268 – 2681P → 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.
Natural varianti271 – 2711G → V in strain: Isolate clinical h12.
Natural varianti279 – 2791G → D in strain: Isolate clinical h11, Isolate clinical h12.
Natural varianti286 – 2861D → 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.
Natural varianti287 – 2871T → M in strain: Isolate CL23; acyclovir resistant. 1 Publication
Natural varianti316 – 3161A → V in strain: Isolate clinical h15.
Natural varianti317 – 3171K → R in strain: Isolate clinical h4.
Natural varianti332 – 3321S → A in strain: Isolate clinical h17.
Natural varianti336 – 3361C → Y in strain: Isolate CL24; acyclovir resistant. 1 Publication
Natural varianti348 – 3481V → I in strain: Isolate clinical h20.
Natural varianti355 – 3551P → Q in strain: Isolate clinical h23 and Isolate clinical h24.
Natural varianti364 – 3641L → P in strain: Isolate clinical BR/2.
Natural varianti374 – 3741E → A in strain: Isolate clinical CH/1.
Natural varianti376 – 3761N → H in strain: Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.

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

ProteinModelPortali Q9QNF7.
SMRi Q9QNF7. Positions 46-376.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q9QNF7. 3 interactions.

Chemistry

BindingDBi Q9QNF7.
ChEMBLi CHEMBL1795127.
DrugBanki DB00249. Idoxuridine.
DB00577. Valaciclovir.
DB00194. Vidarabine.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

SABIO-RK Q9QNF7.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view ]
Pfami PF00693. Herpes_TK. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Genetic characterization of thymidine kinase from acyclovir-resistant and -susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients."
    Morfin F., Souillet G., Bilger K., Ooka T., Aymard M., Thouvenot D.
    J. Infect. Dis. 182:290-293(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], 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.
  2. "Comparison of polymorphism of thymidine kinase gene and restriction fragment length polymorphism of genomic DNA in herpes simplex virus type 1."
    Nagamine M., Suzutani T., Saijo M., Hayashi K., Azuma M.
    J. Clin. Microbiol. 38:2750-2752(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: 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.
  3. "Genotypic and phenotypic characterization of the thymidine kinase of ACV-resistant HSV-1 derived from an acyclovir-sensitive herpes simplex virus type 1 strain."
    Saijo M., Suzutani T., De Clercq E., Niikura M., Maeda A., Morikawa S., Kurane I.
    Antiviral Res. 56:253-262(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], 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.

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 29, 2014
This is version 54 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

External Data

Dasty 3