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P17402

- KITH_HHV1K

UniProt

P17402 - KITH_HHV1K

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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

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
Complete GO annotation...

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

« Hide

        10         20         30         40         50
MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL
60 70 80 90 100
RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI
110 120 130 140 150
YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS
160 170 180 190 200
HAPPPALTLI FDRHPIAALL CYPAARYLMG SMTPQAVLAF VALIPPTLPG
210 220 230 240 250
TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG LLANTVRYLQ
260 270 280 290 300
GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
310 320 330 340 350
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT
360 370
HVTTPGSIPT ICDLARMFAR EMGEAN
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