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P17402

- KITH_HHV1K

UniProt

P17402 - KITH_HHV1K

Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (strain KOS) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 62 (01 Oct 2014)
      Sequence version 1 (01 Aug 1990)
      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.1 Publication

    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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thymidine kinase (EC:2.7.1.21)
    Gene namesi
    Name:TK
    Synonyms:UL23
    OrganismiHuman herpesvirus 1 (strain KOS) (HHV-1) (Human herpes simplex virus 1)
    Taxonomic identifieri10306 [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_0000175072Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP17402.
    SMRiP17402. 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.

    P17402-1 [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 ICDLARMFAR EMGEAN 376
    Length:376
    Mass (Da):40,927
    Last modified:August 1, 1990 - v1
    Checksum:i86BE4A947F9AB1C7
    GO

    Sequence cautioni

    The sequence AAA45817.1 differs from that shown. Reason: Erroneous initiation.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti175 – 1751A → T in mutant KG111.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04327 Genomic DNA. Translation: AAA45817.1. Different initiation.
    PIRiA31291. KIBEKS.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04327 Genomic DNA. Translation: AAA45817.1 . Different initiation.
    PIRi A31291. KIBEKS.

    3D structure databases

    ProteinModelPortali P17402.
    SMRi P17402. Positions 46-376.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    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. "Effect of an amber mutation in the herpes simplex virus thymidine kinase gene on polypeptide synthesis and stability."
      Irmiere A.F., Manos M.M., Jacobson J.G., Gibbs J.S., Coen D.M.
      Virology 168:210-220(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate."
      Coen D.M., Kosz-Vnenchak M., Jacobson J.G., Leib D.A., Bogard C.L., Schaffer P.A., Tyler K.L., Knipe D.M.
      Proc. Natl. Acad. Sci. U.S.A. 86:4736-4740(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiKITH_HHV1K
    AccessioniPrimary (citable) accession number: P17402
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: August 1, 1990
    Last modified: October 1, 2014
    This is version 62 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 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 HSV 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.

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3