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P03176 (KITH_HHV11) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
ORF Names:UL23
OrganismHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]
Taxonomic identifier10299 [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. Ref.8

Subunit structure

Homodimer. Ref.8

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
   Developmental stageEarly protein
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
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_0000175069

Regions

Nucleotide binding56 – 638ATP

Sites

Active site831Proton acceptor Potential
Binding site1011Substrate
Binding site1251Substrate
Binding site2161ATP
Binding site2221Substrate

Natural variations

Natural variant61C → G.
Natural variant231N → S.
Natural variant361E → K.
Natural variant421P → L.
Natural variant2511C → G.

Experimental info

Sequence conflict2651T → A in CAA32315. Ref.2
Sequence conflict3211S → P in CAA32315. Ref.2

Secondary structure

.............................................................. 376
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03176 [UniParc].

Last modified July 15, 1998. Version 4.
Checksum: 7E58BB575143B328

FASTA37640,972
        10         20         30         40         50         60 
MASYPCHQHA SAFDQAARSR GHNNRRTALR PRRQQEATEV RPEQKMPTLL RVYIDGPHGM 

        70         80         90        100        110        120 
GKTTTTQLLV ALGSRDDIVY VPEPMTYWRV 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 CGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 

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

       370 
ICDLARTFAR EMGEAN 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V00470 Genomic DNA. Translation: CAA23742.1.
X14112 Genomic DNA. Translation: CAA32315.1.
PIRKIBE17. E30084.
RefSeqNP_044624.1. NC_001806.1.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
DisProtDP00419.
ProteinModelPortalP03176.
SMRP03176. Positions 46-376.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP03176.
DrugBankDB00787. Aciclovir.
DB01004. Ganciclovir.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2703374.

Phylogenomic databases

ProtClustDBPHA3133.

Enzyme and pathway databases

BRENDA2.7.1.21. 2649.
SABIO-RKP03176.

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...

Other

EvolutionaryTraceP03176.

Entry information

Entry nameKITH_HHV11
AccessionPrimary (citable) accession number: P03176
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 96 of the entry and version 4 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references