Thymidine kinase - Human herpesvirus 1 (HHV-1)

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Q9QNF7 (KITH_HHV1) Reviewed, UniProtKB/Swiss-Prot

Last modified May 31, 2011. Version 42. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Thymidine kinase
EC=2.7.1.21

Gene names

Name:	TK
Synonyms:	UL23

Organism

Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1)

Taxonomic identifier

10298 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	376 AA.
Sequence status	Complete.
Protein existence	Evidence 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 herpesviruses thymidine kinase family.

Ontologies

Keywords
Biological process	DNA synthesis
Developmental stage	Early protein
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW TMP biosynthetic process Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW thymidine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 376

376

Thymidine kinase

PRO_0000175068

Regions

Nucleotide binding

56 – 63

ATP By similarity

Sites

Active site

Proton acceptor Potential

Binding site

101

Substrate By similarity

Binding site

125

Substrate By similarity

Binding site

172

Substrate By similarity

Binding site

216

ATP By similarity

Natural variations

Natural variant

C → 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 variant

A → V in strain: Isolate clinical CH/1.

Natural variant

S → N in strain: Isolate clinical h3.

Natural variant

L → V in strain: Isolate clinical h17.

Natural variant

R → H in strain: Isolate clinical h4.

Natural variant

L → P in strain: Isolate clinical h21, Isolate clinical h22, Isolate clinical h23, Isolate clinical h24, Isolate clinical h25, Isolate clinical CH/1.

Natural variant

R → W in strain: Isolate clinical HE/2; acyclovir resistant. Ref.1

Natural variant

D → N in strain: Isolate CL17; acyclovir resistant. Ref.3

Natural variant

T → N in strain: Isolate CL18; acyclovir resistant. Ref.3

Natural variant

E → K in strain: Isolate clinical LA/2; acyclovir resistant. Ref.1

Natural variant

P → S in strain: Isolate CL19; acyclovir resistant. Ref.3

Natural variant

M → I in strain: Isolate clinical VA/1.

Natural variant

Q → 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 variant

105

H → P in strain: Isolate clinical CH/1; acyclovir resistant. Ref.1

Natural variant

158

T → A in strain: Isolate clinical h20.

Natural variant

158

T → I in strain: Isolate clinical h13.

Natural variant

173

P → R in strain: Isolate CL20; acyclovir resistant. Ref.3

Natural variant

175

A → V in strain: Isolate clinical BR/2; acyclovir resistant. Ref.1

Natural variant

191

V → L in strain: Isolate clinical h3.

Natural variant

192

A → V in strain: Isolate clinical LA/1 and Isolate clinical LA/2; acyclovir resistant.

Natural variant

200

G → C in strain: Isolate CL21; acyclovir resistant. Ref.3

Natural variant

212

R → K in strain: Isolate clinical h5.

Natural variant

240

G → E in strain: Isolate clinical BR/1, Isolate clinical BR/2, Isolate clinical CH/1 and Isolate clinical VA/1.

Natural variant

243

A → V in strain: Isolate clinical h5.

Natural variant

245

T → M in strain: Isolate CL22; acyclovir resistant. Ref.3

Natural variant

251

G → A in strain: Isolate clinical h25.

Natural variant

251

G → 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 variant

257

E → Q in strain: Isolate clinical h25.

Natural variant

267

V → L in strain: Isolate clinical CH/1, Isolate clinical LA/1, Isolate clinical LA/2 and Isolate clinical MA/1.

Natural variant

268

P → 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 variant

271

G → V in strain: Isolate clinical h12.

Natural variant

279

G → D in strain: Isolate clinical h11, Isolate clinical h12.

Natural variant

286

D → 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 variant

287

T → M in strain: Isolate CL23; acyclovir resistant. Ref.3

Natural variant

316

A → V in strain: Isolate clinical h15.

Natural variant

317

K → R in strain: Isolate clinical h4.

Natural variant

332

S → A in strain: Isolate clinical h17.

Natural variant

336

C → Y in strain: Isolate CL24; acyclovir resistant. Ref.3

Natural variant

348

V → I in strain: Isolate clinical h20.

Natural variant

355

P → Q in strain: Isolate clinical h23 and Isolate clinical h24.

Natural variant

364

L → P in strain: Isolate clinical BR/2.

Natural variant

374

E → A in strain: Isolate clinical CH/1.

Natural variant

376

N → H in strain: Isolate clinical MA/1, Isolate clinical PR/1 and Isolate clinical PR/2.

Sequences

Sequence

Length

Mass (Da)

Tools

Q9QNF7 [UniParc].

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

376

40,897

        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

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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: 10882609] [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: 10878078] [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: 12406508] [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.
+	Additional computationally mapped references.

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
ProteinModelPortal	Q9QNF7.
SMR	Q9QNF7. Positions 46-376.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR001889. Herpes_TK. [Graphical view]
Pfam	PF00693. Herpes_TK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00432. Trifluridine. DB00577. Valaciclovir. DB00194. Vidarabine.

Entry information

Entry name

KITH_HHV1

Accession

Primary (citable) accession number: Q9QNF7
Secondary accession number(s): Q9ENR2

Q9IZ09

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	May 1, 2000
Last modified:	May 31, 2011
This is version 42 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Family and domain databases

Other

Entry information

Relevant documents