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P03176

- KITH_HHV11

UniProt

P03176 - KITH_HHV11

Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 99 (01 Oct 2014)
      Sequence version 4 (15 Jul 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.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei83 – 831Proton acceptorSequence Analysis
    Binding sitei101 – 1011Substrate
    Binding sitei125 – 1251Substrate
    Binding sitei216 – 2161ATP
    Binding sitei222 – 2221Substrate

    Regions

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

    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

    BRENDAi2.7.1.21. 2649.
    SABIO-RKP03176.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thymidine kinase (EC:2.7.1.21)
    Gene namesi
    Name:TK
    ORF Names:UL23
    OrganismiHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
    Taxonomic identifieri10299 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000009294: Genome

    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_0000175069Add
    BLAST

    Expressioni

    Keywords - Developmental stagei

    Early protein

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Structurei

    Secondary structure

    1
    376
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi48 – 547
    Beta strandi56 – 616
    Helixi62 – 698
    Helixi70 – 723
    Turni75 – 773
    Beta strandi78 – 814
    Helixi85 – 895
    Beta strandi92 – 943
    Helixi96 – 10813
    Helixi114 – 13926
    Helixi140 – 1423
    Beta strandi143 – 1486
    Beta strandi150 – 1523
    Beta strandi156 – 1627
    Helixi165 – 1695
    Helixi171 – 1788
    Helixi184 – 1929
    Beta strandi202 – 2076
    Helixi210 – 21910
    Turni222 – 2243
    Helixi229 – 25022
    Helixi255 – 2584
    Helixi259 – 2624
    Beta strandi276 – 2805
    Helixi284 – 2863
    Helixi288 – 2925
    Helixi295 – 2973
    Beta strandi302 – 3043
    Helixi306 – 32015
    Beta strandi323 – 3286
    Helixi333 – 34311
    Helixi344 – 3463
    Beta strandi349 – 3546
    Helixi357 – 37216

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E2HX-ray1.90A/B46-376[»]
    1E2IX-ray1.90A/B46-376[»]
    1E2JX-ray2.50A/B46-376[»]
    1E2KX-ray1.70A/B46-376[»]
    1E2LX-ray2.40A/B46-376[»]
    1E2MX-ray2.20A/B46-376[»]
    1E2NX-ray2.20A/B46-376[»]
    1E2PX-ray2.50A/B46-376[»]
    1KI2X-ray2.20A/B46-376[»]
    1KI3X-ray2.37A/B46-376[»]
    1KI4X-ray2.34A/B46-376[»]
    1KI6X-ray2.37A/B46-376[»]
    1KI7X-ray2.20A/B46-376[»]
    1KI8X-ray2.20A/B46-376[»]
    1KIMX-ray2.14A/B11-376[»]
    1OF1X-ray1.95A/B1-376[»]
    1P7CX-ray2.10A/B34-376[»]
    1QHIX-ray1.90A/B11-376[»]
    1VTKX-ray2.75A34-376[»]
    2KI5X-ray1.90A/B11-376[»]
    2VTKX-ray2.80A34-376[»]
    3F0TX-ray2.00A/B45-376[»]
    3RDPX-ray2.80A/B46-376[»]
    3VTKX-ray3.00A34-376[»]
    4IVPX-ray2.10A/B46-376[»]
    4IVQX-ray1.90A/B46-376[»]
    4IVRX-ray2.40A/B46-376[»]
    4JBXX-ray2.10A/B45-376[»]
    4JBYX-ray2.00A/B45-376[»]
    DisProtiDP00419.
    ProteinModelPortaliP03176.
    SMRiP03176. Positions 46-376.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03176.

    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.

    P03176-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASYPCHQHA SAFDQAARSR GHNNRRTALR 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
    CGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 300
    NGDLYNVFAW ALDVLAKRLR SMHVFILDYD QSPAGCRDAL LQLTSGMVQT 350
    HVTTPGSIPT ICDLARTFAR EMGEAN 376
    Length:376
    Mass (Da):40,972
    Last modified:July 15, 1998 - v4
    Checksum:i7E58BB575143B328
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti265 – 2651T → A in CAA32315. (PubMed:2839594)Curated
    Sequence conflicti321 – 3211S → P in CAA32315. (PubMed:2839594)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti6 – 61C → G.
    Natural varianti23 – 231N → S.
    Natural varianti36 – 361E → K.
    Natural varianti42 – 421P → L.
    Natural varianti251 – 2511C → G.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V00470 Genomic DNA. Translation: CAA23742.1.
    X14112 Genomic DNA. Translation: CAA32315.1.
    PIRiE30084. KIBE17.
    RefSeqiNP_044624.1. NC_001806.1.

    Genome annotation databases

    GeneIDi2703374.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V00470 Genomic DNA. Translation: CAA23742.1 .
    X14112 Genomic DNA. Translation: CAA32315.1 .
    PIRi E30084. KIBE17.
    RefSeqi NP_044624.1. NC_001806.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1E2H X-ray 1.90 A/B 46-376 [» ]
    1E2I X-ray 1.90 A/B 46-376 [» ]
    1E2J X-ray 2.50 A/B 46-376 [» ]
    1E2K X-ray 1.70 A/B 46-376 [» ]
    1E2L X-ray 2.40 A/B 46-376 [» ]
    1E2M X-ray 2.20 A/B 46-376 [» ]
    1E2N X-ray 2.20 A/B 46-376 [» ]
    1E2P X-ray 2.50 A/B 46-376 [» ]
    1KI2 X-ray 2.20 A/B 46-376 [» ]
    1KI3 X-ray 2.37 A/B 46-376 [» ]
    1KI4 X-ray 2.34 A/B 46-376 [» ]
    1KI6 X-ray 2.37 A/B 46-376 [» ]
    1KI7 X-ray 2.20 A/B 46-376 [» ]
    1KI8 X-ray 2.20 A/B 46-376 [» ]
    1KIM X-ray 2.14 A/B 11-376 [» ]
    1OF1 X-ray 1.95 A/B 1-376 [» ]
    1P7C X-ray 2.10 A/B 34-376 [» ]
    1QHI X-ray 1.90 A/B 11-376 [» ]
    1VTK X-ray 2.75 A 34-376 [» ]
    2KI5 X-ray 1.90 A/B 11-376 [» ]
    2VTK X-ray 2.80 A 34-376 [» ]
    3F0T X-ray 2.00 A/B 45-376 [» ]
    3RDP X-ray 2.80 A/B 46-376 [» ]
    3VTK X-ray 3.00 A 34-376 [» ]
    4IVP X-ray 2.10 A/B 46-376 [» ]
    4IVQ X-ray 1.90 A/B 46-376 [» ]
    4IVR X-ray 2.40 A/B 46-376 [» ]
    4JBX X-ray 2.10 A/B 45-376 [» ]
    4JBY X-ray 2.00 A/B 45-376 [» ]
    DisProti DP00419.
    ProteinModelPortali P03176.
    SMRi P03176. Positions 46-376.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P03176.
    DrugBanki DB00787. Aciclovir.
    DB01004. Ganciclovir.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 2703374.

    Enzyme and pathway databases

    BRENDAi 2.7.1.21. 2649.
    SABIO-RK P03176.

    Miscellaneous databases

    EvolutionaryTracei P03176.

    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. "The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene."
      McKnight S.L.
      Nucleic Acids Res. 8:5949-5964(1980) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1."
      McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P.
      J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The three-dimensional structure of thymidine kinase from herpes simplex virus type 1."
      Wild K., Bohner T., Aubry A., Folkers G., Schulz G.E.
      FEBS Lett. 368:289-292(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-376.
    4. "Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir."
      Brown D.G., Visse R., Sandhu G., Davies A., Rizkallah P.J., Melitz C., Summers W.C., Sanderson M.R.
      Nat. Struct. Biol. 2:876-881(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
    5. "The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue."
      Wild K., Bohner T., Folkers G., Schulz G.E.
      Protein Sci. 6:2097-2106(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 34-376.
    6. "Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands."
      Champness J.N., Bennett M.S., Wien F., Visse R., Summers W.C., Herdewijn P., de Clerq E., Ostrowski T., Jarvest R.L., Sanderson M.R.
      Proteins 32:350-361(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
    7. "Structure to 1.9-A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir."
      Bennett M.S., Wien F., Champness J.N., Batuwangala T., Rutherford T., Summers W.C., Sun H., Wright G., Sanderson M.R.
      FEBS Lett. 443:121-125(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
    8. "Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography."
      Vogt J., Perozzo R., Pautsch A., Prota A., Schelling P., Pilger B., Folkers G., Scapozza L., Schulz G.E.
      Proteins 41:545-553(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 45-376 IN COMPLEX WITH ADENINE ANALOG, CATALYTIC ACTIVITY, SUBUNIT.

    Entry informationi

    Entry nameiKITH_HHV11
    AccessioniPrimary (citable) accession number: P03176
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 15, 1998
    Last modified: October 1, 2014
    This is version 99 of the entry and version 4 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.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3