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Q9QNF7 (KITH_HHV1) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 52. 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 (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifier10298 [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 used to treat herpes simplex infections 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 HHV 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.

The sequence shown is that of strain TAS.

Sequence similarities

Belongs to the herpesviridae thymidine kinase family.

Ontologies

Keywords
   Biological processDNA synthesis
   Developmental stageEarly protein
   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_0000175068

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 variant61C → G in strain: Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical LA/1, Isolate clinical LA/2 and Isolate clinical MA/1.
Natural variant171A → V in strain: Isolate clinical CH/1.
Natural variant231S → N in strain: Isolate clinical h3.
Natural variant291L → V in strain: Isolate clinical h17.
Natural variant411R → H in strain: Isolate clinical h4.
Natural variant421L → P in strain: Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical CH/1.
Natural variant511R → W in strain: Isolate clinical HE/2; acyclovir resistant. Ref.1
Natural variant551D → N in strain: Isolate CL17; acyclovir resistant. Ref.3
Natural variant651T → N in strain: Isolate CL18; acyclovir resistant. Ref.3
Natural variant831E → K in strain: Isolate clinical LA/2; acyclovir resistant. Ref.1
Natural variant841P → S in strain: Isolate CL19; acyclovir resistant. Ref.3
Natural variant851M → I in strain: Isolate clinical VA/1.
Natural variant891Q → R in strain: Isolate clinical CH/1, Isolate clinical h20, Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.
Natural variant1051H → P in strain: Isolate clinical CH/1; acyclovir resistant. Ref.1
Natural variant1581T → A in strain: Isolate clinical h20.
Natural variant1581T → I in strain: Isolate clinical h13.
Natural variant1731P → R in strain: Isolate CL20; acyclovir resistant. Ref.3
Natural variant1751A → V in strain: Isolate clinical BR/2; acyclovir resistant. Ref.1
Natural variant1911V → L in strain: Isolate clinical h3.
Natural variant1921A → V in strain: Isolate clinical LA/1 and Isolate clinical LA/2; acyclovir resistant.
Natural variant2001G → C in strain: Isolate CL21; acyclovir resistant. Ref.3
Natural variant2121R → K in strain: Isolate clinical h5.
Natural variant2401G → E in strain: Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1 and Isolate clinical VA/1.
Natural variant2431A → V in strain: Isolate clinical h5.
Natural variant2451T → M in strain: Isolate CL22; acyclovir resistant. Ref.3
Natural variant2511G → A in strain: Isolate clinical h25.
Natural variant2511G → C in strain: Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.
Natural variant2571E → Q in strain: Isolate clinical h25.
Natural variant2671V → L in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2 and Isolate clinical MA/1.
Natural variant2681P → T in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.
Natural variant2711G → V in strain: Isolate clinical h12.
Natural variant2791G → D in strain: Isolate clinical h11, Isolate clinical h12.
Natural variant2861D → E in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.
Natural variant2871T → M in strain: Isolate CL23; acyclovir resistant. Ref.3
Natural variant3161A → V in strain: Isolate clinical h15.
Natural variant3171K → R in strain: Isolate clinical h4.
Natural variant3321S → A in strain: Isolate clinical h17.
Natural variant3361C → Y in strain: Isolate CL24; acyclovir resistant. Ref.3
Natural variant3481V → I in strain: Isolate clinical h20.
Natural variant3551P → Q in strain: Isolate clinical h23 and Isolate clinical h24.
Natural variant3641L → P in strain: Isolate clinical BR/2.
Natural variant3741E → A in strain: Isolate clinical CH/1.
Natural variant3761N → H in strain: Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.

Sequences

Sequence LengthMass (Da)Tools
Q9QNF7 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 86A177947F9AB1C7

FASTA37640,897
        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 
ICDLARTFAR EMGEAN 

« Hide

References

[1]"Genetic characterization of thymidine kinase from acyclovir-resistant and -susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients."
Morfin F., Souillet G., Bilger K., Ooka T., Aymard M., Thouvenot D.
J. Infect. Dis. 182:290-293(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ACYCLOVIR RESISTANT TRP-51; LYS-83; PRO-105 AND VAL-175.
Strain: Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1, Isolate clinical HE/1, Isolate clinical HE/2, Isolate clinical LA/1, Isolate clinical LA/2, Isolate clinical MA/1, Isolate clinical MO/1, Isolate clinical PR/1, Isolate clinical PR/2 and Isolate clinical VA/1.
[2]"Comparison of polymorphism of thymidine kinase gene and restriction fragment length polymorphism of genomic DNA in herpes simplex virus type 1."
Nagamine M., Suzutani T., Saijo M., Hayashi K., Azuma M.
J. Clin. Microbiol. 38:2750-2752(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate clinical h1, Isolate clinical h10, Isolate clinical h11, Isolate clinical h12, Isolate clinical h13, Isolate clinical h14, Isolate clinical h15, Isolate clinical h16, Isolate clinical h17, Isolate clinical h18, Isolate clinical h19, Isolate clinical h2, Isolate clinical h20, Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical h3, Isolate clinical h4, Isolate clinical h5, Isolate clinical h6, Isolate clinical h7, Isolate clinical h8 and Isolate clinical h9.
[3]"Genotypic and phenotypic characterization of the thymidine kinase of ACV-resistant HSV-1 derived from an acyclovir-sensitive herpes simplex virus type 1 strain."
Saijo M., Suzutani T., De Clercq E., Niikura M., Maeda A., Morikawa S., Kurane I.
Antiviral Res. 56:253-262(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ACYCLOVIR RESISTANT ASN-55; ASN-65; SER-84; ARG-173; CYS-200; MET-245; MET-287 AND TYR-336.
Strain: Isolate CL17, Isolate CL18, Isolate CL19, Isolate CL20, Isolate CL21, Isolate CL22, Isolate CL23, Isolate CL24 and TAS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF243477 Genomic DNA. Translation: AAF72491.1.
AF243478 Genomic DNA. Translation: AAF72492.1.
AF243479 Genomic DNA. Translation: AAF72493.1.
AF243481 Genomic DNA. Translation: AAF72495.1.
AF243482 Genomic DNA. Translation: AAF72496.1.
AF243483 Genomic DNA. Translation: AAF72497.1.
AF243486 Genomic DNA. Translation: AAF72500.1.
AF243487 Genomic DNA. Translation: AAF72501.1.
AF243488 Genomic DNA. Translation: AAF72502.1.
AF243492 Genomic DNA. Translation: AAF72506.1.
AF243493 Genomic DNA. Translation: AAF72507.1.
AF243494 Genomic DNA. Translation: AAF72508.1.
AB009260 Genomic DNA. Translation: BAA83999.1.
AB032866 Genomic DNA. Translation: BAA93054.1.
AB032867 Genomic DNA. Translation: BAA93055.1.
AB032868 Genomic DNA. Translation: BAA93056.1.
AB032869 Genomic DNA. Translation: BAA93057.1.
AB032870 Genomic DNA. Translation: BAA93058.1.
AB032871 Genomic DNA. Translation: BAA93059.1.
AB032872 Genomic DNA. Translation: BAA93060.1.
AB032873 Genomic DNA. Translation: BAA93061.1.
AB032874 Genomic DNA. Translation: BAA93062.1.
AB032875 Genomic DNA. Translation: BAA93063.1.
AB032876 Genomic DNA. Translation: BAA93064.1.
AB032877 Genomic DNA. Translation: BAA93065.1.
AB032878 Genomic DNA. Translation: BAA93066.1.
AB032879 Genomic DNA. Translation: BAA93067.1.
AB032880 Genomic DNA. Translation: BAA93068.1.
AB032881 Genomic DNA. Translation: BAA93069.1.
AB032882 Genomic DNA. Translation: BAA93070.1.
AB032883 Genomic DNA. Translation: BAA93071.1.
AB032884 Genomic DNA. Translation: BAA93072.1.
AB032885 Genomic DNA. Translation: BAA93073.1.
AB032886 Genomic DNA. Translation: BAA93074.1.
AB032887 Genomic DNA. Translation: BAA93075.1.
AB032888 Genomic DNA. Translation: BAA93076.1.
AB032889 Genomic DNA. Translation: BAA93077.1.
AB032890 Genomic DNA. Translation: BAA93078.1.
AB047358 Genomic DNA. Translation: BAB11915.1.
AB047371 Genomic DNA. Translation: BAB11948.1.
AB047372 Genomic DNA. Translation: BAB11949.1.
AB047373 Genomic DNA. Translation: BAB11950.1.
AB047374 Genomic DNA. Translation: BAB11951.1.
AB047375 Genomic DNA. Translation: BAB11952.1.
AB047376 Genomic DNA. Translation: BAB11953.1.
AB047377 Genomic DNA. Translation: BAB11954.1.
AB047378 Genomic DNA. Translation: BAB11955.1.

3D structure databases

ProteinModelPortalQ9QNF7.
SMRQ9QNF7. Positions 46-376.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ9QNF7.
ChEMBLCHEMBL1795127.
DrugBankDB00432. Trifluridine.
DB00577. Valaciclovir.
DB00194. Vidarabine.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKQ9QNF7.

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_HHV1
AccessionPrimary (citable) accession number: Q9QNF7
Secondary accession number(s): Q9ENR2 expand/collapse secondary AC list , Q9ENR3, Q9ENR4, Q9ENR5, Q9ENR6, Q9ENR7, Q9ENR8, Q9ENR9, Q9ICF2, Q9ICF3, Q9ICH1, Q9IR31, Q9IR32, Q9IR33, Q9IR34, Q9IR35, Q9IR36, Q9IR37, Q9IR38, Q9IR39, Q9IR40, Q9IYZ6, Q9IZ00, Q9IZ01, Q9IZ04, Q9IZ05, Q9IZ06, Q9IZ08, Q9IZ09
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 52 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