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P06479

- KITH_HHV1S

UniProt

P06479 - KITH_HHV1S

Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (strain SC16) (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 60 (01 Oct 2014)
      Sequence version 1 (01 Nov 1988)
      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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thymidine kinase (EC:2.7.1.21)
    Gene namesi
    Name:TK
    Synonyms:UL23
    OrganismiHuman herpesvirus 1 (strain SC16) (HHV-1) (Human herpes simplex virus 1)
    Taxonomic identifieri10309 [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_0000175073Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP06479.
    SMRiP06479. 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.

    P06479-1 [UniParc]FASTAAdd to Basket

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    MASYPGHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RPEQKMPTLL    50
    RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWRV 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 LQLTSGMIQT 350
    HVTTPGSIPT ICDLARTFAR EMGEAN 376
    Length:376
    Mass (Da):40,877
    Last modified:November 1, 1988 - v1
    Checksum:i5B661B145585125A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X03764 Genomic DNA. Translation: CAA27395.1.
    PIRiA27240. KIBE16.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X03764 Genomic DNA. Translation: CAA27395.1 .
    PIRi A27240. KIBE16.

    3D structure databases

    ProteinModelPortali P06479.
    SMRi P06479. Positions 46-376.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P06479.
    ChEMBLi CHEMBL1820.

    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. "Evidence that the 'active centre' of the herpes simplex virus thymidine kinase involves an interaction between three distinct regions of the polypeptide."
      Darby G., Larder B.A., Inglis M.M.
      J. Gen. Virol. 67:753-758(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

    Entry informationi

    Entry nameiKITH_HHV1S
    AccessioniPrimary (citable) accession number: P06479
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: November 1, 1988
    Last modified: October 1, 2014
    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 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