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P17402 (KITH_HHV1K) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 61. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thymidine kinase

EC=2.7.1.21
Gene names
Name:TK
Synonyms:UL23
OrganismHuman herpesvirus 1 (strain KOS) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifier10306 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length376 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Catalytic activity

ATP + thymidine = ADP + thymidine 5'-phosphate.

Subunit structure

Homodimer By similarity.

Biotechnological use

Used in molecular biology as a selectable marker to identify transfected eukaryotic cells. Used in cancer suicide gene therapy to selectively kill transformed cells.

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.

Sequence similarities

Belongs to the herpesviridae thymidine kinase family.

Sequence caution

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

Ontologies

Keywords
   Biological processDNA synthesis
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-KW

TMP biosynthetic process

Inferred from electronic annotation. Source: InterPro

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

thymidine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 376376Thymidine kinase
PRO_0000175072

Regions

Nucleotide binding56 – 638ATP By similarity

Sites

Active site831Proton acceptor Potential
Binding site1011Substrate By similarity
Binding site1251Substrate By similarity
Binding site1721Substrate By similarity
Binding site2161ATP By similarity

Natural variations

Natural variant1751A → T in mutant KG111.

Sequences

Sequence LengthMass (Da)Tools
P17402 [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: 86BE4A947F9AB1C7

FASTA37640,927
        10         20         30         40         50         60 
MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL RVYIDGPHGM 

        70         80         90        100        110        120 
GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI YTTQHRLDQG EISAGDAAVV 

       130        140        150        160        170        180 
MTSAQITMGM PYAVTDAVLA PHIGGEAGSS HAPPPALTLI FDRHPIAALL CYPAARYLMG 

       190        200        210        220        230        240 
SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG 

       250        260        270        280        290        300 
LLANTVRYLQ GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 

       310        320        330        340        350        360 
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT HVTTPGSIPT 

       370 
ICDLARMFAR EMGEAN 

« Hide

References

[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04327 Genomic DNA. Translation: AAA45817.1. Different initiation.
PIRKIBEKS. A31291.

3D structure databases

ProteinModelPortalP17402.
SMRP17402. Positions 46-376.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF00693. Herpes_TK. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Entry information

Entry nameKITH_HHV1K
AccessionPrimary (citable) accession number: P17402
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: April 16, 2014
This is version 61 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families