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Q9QNF7

- KITH_HHV1

UniProt

Q9QNF7 - KITH_HHV1

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
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    • History
      Entry version 53 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    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

    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

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    MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL    50
    RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI 100
    YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS 150
    HAPPPALTLI FDRHPIAALL CYPAARYLMG SMTPQAVLAF VALIPPTLPG 200
    TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG LLANTVRYLQ 250
    GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 300
    NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT 350
    HVTTPGSIPT ICDLARTFAR EMGEAN 376
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 DB00432. Trifluridine.
    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 1, 2014
    This is version 53 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