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P04407 (KITH_HHV23) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 64. 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
OrganismHuman herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2)
Taxonomic identifier10313 [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 By similarity.

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.

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_0000175074

Regions

Nucleotide binding56 – 638ATP By similarity

Sites

Active site841Proton acceptor Potential
Binding site1021Substrate By similarity
Binding site1261Substrate By similarity
Binding site1731Substrate By similarity
Binding site2171ATP By similarity

Experimental info

Sequence conflict2711Missing in CAA25858. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P04407 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 0B1D68B0BBA3C8A5

FASTA37640,467
        10         20         30         40         50         60 
MASHAGQQHA PAFGQAARAS GPTDGRAASR PSHRQGASEA RGDPELPTLL RVYIDGPHGV 

        70         80         90        100        110        120 
GKTTTSAQLM EALGPRDNIV YVPEPMTYWQ VLGASETLTN IYNTQHRLDR GEISAGEAAV 

       130        140        150        160        170        180 
VMTSAQITMS TPYAATDAVL APHIGGEAVG PQAPPPALTL VFDRHPIASL LCYPAARYLM 

       190        200        210        220        230        240 
GSMTPQAVLA FVALMPPTAP GTNLVLGVLP EAEHADRLAR RQRPGERLDL AMLSAIRRVY 

       250        260        270        280        290        300 
DLLANTVRYL QRGGRWREDW GRLTGVAAAT PRPDPEDGAG SLPRIEDTLF ALFRVPELLA 

       310        320        330        340        350        360 
PNGDLYHIFA WVLDVLADRL LPMHLFVLDY DQSPVGCRDA LLRLTAGMIP TRVTTAGSIA 

       370 
EIRDLARTFA REVGGV 

« Hide

References

[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].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X01712 Genomic DNA. Translation: CAA25858.1.
V00466 Genomic DNA. Translation: CAA23740.1.
M29942 Genomic DNA. Translation: AAA45856.1.
PIRKIBET3. A90648.

3D structure databases

ProteinModelPortalP04407.
SMRP04407. Positions 46-374.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP04407.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

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_HHV23
AccessionPrimary (citable) accession number: P04407
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: December 15, 1998
Last modified: March 19, 2014
This is version 64 of the entry and version 2 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