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P04407

- KITH_HHV23

UniProt

P04407 - KITH_HHV23

Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 67 (01 Oct 2014)
      Sequence version 2 (15 Dec 1998)
      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 sitei84 – 841Proton acceptorSequence Analysis
    Binding sitei102 – 1021SubstrateBy similarity
    Binding sitei126 – 1261SubstrateBy similarity
    Binding sitei173 – 1731SubstrateBy similarity
    Binding sitei217 – 2171ATPBy 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
    OrganismiHuman herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2)
    Taxonomic identifieri10313 [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_0000175074Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP04407.
    SMRiP04407. Positions 46-374.
    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.

    P04407-1 [UniParc]FASTAAdd to Basket

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    MASHAGQQHA PAFGQAARAS GPTDGRAASR PSHRQGASEA RGDPELPTLL    50
    RVYIDGPHGV GKTTTSAQLM EALGPRDNIV YVPEPMTYWQ VLGASETLTN 100
    IYNTQHRLDR GEISAGEAAV VMTSAQITMS TPYAATDAVL APHIGGEAVG 150
    PQAPPPALTL VFDRHPIASL LCYPAARYLM GSMTPQAVLA FVALMPPTAP 200
    GTNLVLGVLP EAEHADRLAR RQRPGERLDL AMLSAIRRVY DLLANTVRYL 250
    QRGGRWREDW GRLTGVAAAT PRPDPEDGAG SLPRIEDTLF ALFRVPELLA 300
    PNGDLYHIFA WVLDVLADRL LPMHLFVLDY DQSPVGCRDA LLRLTAGMIP 350
    TRVTTAGSIA EIRDLARTFA REVGGV 376
    Length:376
    Mass (Da):40,467
    Last modified:December 15, 1998 - v2
    Checksum:i0B1D68B0BBA3C8A5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti271 – 2711Missing in CAA25858. (PubMed:6317035)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X01712 Genomic DNA. Translation: CAA25858.1.
    V00466 Genomic DNA. Translation: CAA23740.1.
    M29942 Genomic DNA. Translation: AAA45856.1.
    PIRiA90648. KIBET3.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X01712 Genomic DNA. Translation: CAA25858.1 .
    V00466 Genomic DNA. Translation: CAA23740.1 .
    M29942 Genomic DNA. Translation: AAA45856.1 .
    PIRi A90648. KIBET3.

    3D structure databases

    ProteinModelPortali P04407.
    SMRi P04407. Positions 46-374.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P04407.

    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. "Nucleotide sequence of the herpes simplex virus type 2 (HSV-2) thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide and its comparison with the HSV-1 thymidine kinase gene."
      Kit S., Kit M., Qavi H., Trkula D., Otsuka H.
      Biochim. Biophys. Acta 741:158-170(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Nucleotide sequence of the herpes simplex virus type 2 thymidine kinase gene."
      Swain M.A., Galloway D.A.
      J. Virol. 46:1045-1050(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Nucleotide sequence changes in thymidine kinase gene of herpes simplex virus type 2 clones from an isolate of a patient treated with acyclovir."
      Kit S., Sheppard M., Ichimura H., Nusinoff-Lehrman S., Ellis M.N., Fyfe J.A., Otsuka H.
      Antimicrob. Agents Chemother. 31:1483-1490(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

    Entry informationi

    Entry nameiKITH_HHV23
    AccessioniPrimary (citable) accession number: P04407
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: December 15, 1998
    Last modified: October 1, 2014
    This is version 67 of the entry and version 2 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