P0C0E6 (KITH_VZVO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine kinase
EC=2.7.1.21

Gene names

ORF Names:

ORF36

Organism

Varicella-zoster virus (strain Oka vaccine) (HHV-3) (Human herpesvirus 3) [Complete proteome]

Taxonomic identifier

341980 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Varicellovirus › Human herpesvirus 3

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	341 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.
Miscellaneous	Phosphorylates and thereby activates certain drugs like acyclovir (ACV), valacyclovir, 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 By similarity.
Sequence similarities	Belongs to the herpesviridae thymidine kinase family.

Ontologies

Keywords
Biological process	DNA synthesis
Developmental stage	Early protein
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome
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 – 341

341

Thymidine kinase

PRO_0000175087

Regions

Nucleotide binding

19 – 26

8

ATP

Sites

Active site

48

1

Proton acceptor Potential

Binding site

66

1

Substrate

Binding site

90

1

Substrate

Binding site

139

1

Substrate By similarity

Binding site

183

1

ATP By similarity

Secondary structure

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341

Helix Strand Turn

Details...

Beta strand

10 – 23

14

Helix

27 – 34

8

Turn

35 – 38

4

Helix

40 – 42

3

Beta strand

43 – 46

4

Helix

50 – 53

4

Helix

61 – 73

13

Helix

79 – 92

14

Helix

94 – 106

13

Beta strand

124 – 130

7

Helix

133 – 136

4

Helix

138 – 145

8

Helix

151 – 153

3

Helix

154 – 158

5

Beta strand

169 – 174

6

Helix

177 – 183

7

Helix

196 – 218

23

Helix

224 – 227

4

Helix

233 – 239

7

Helix

253 – 255

3

Helix

258 – 261

4

Helix

264 – 266

3

Helix

275 – 290

16

Beta strand

292 – 297

6

Helix

302 – 312

11

Helix

313 – 315

3

Beta strand

319 – 321

3

Helix

323 – 336

14

Sequences

	Sequence		Length	Mass (Da)
	P0C0E6 [UniParc]. Last modified September 13, 2005. Version 1. Checksum: F38ACC39751C076A	FASTA	341	37,843
	10 20 30 40 50 60 MSTDKTDVKM GVLRIYLDGA YGIGKTTAAE EFLHHFAITP NRILLIGEPL SYWRNLAGED 70 80 90 100 110 120 AICGIYGTQT RRLNGDVSPE DAQRLTAHFQ SLFCSPHAIM HAKISALMDT STSDLVQVNK 130 140 150 160 170 180 EPYKIMLSDR HPIASTICFP LSRYLVGDMS PAALPGLLFT LPAEPPGTNL VVCTVSLPSH 190 200 210 220 230 240 LSRVSKRARP GETVNLPFVM VLRNVYIMLI NTIIFLKTNN WHAGWNTLSF CNDVFKQKLQ 250 260 270 280 290 300 KSECIKLREV PGIEDTLFAV LKLPELCGEF GNILPLWAWG METLSNCLRS MSPFVLSLEQ 310 320 330 340 TPQHAAQELK TLLPQMTPAN MSSGAWNILK ELVNAVQDNT S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular analysis of the pyrimidine deoxyribonucleoside kinase gene of wild-type and acyclovir-resistant strains of varicella-zoster virus." Sawyer M.H., Inchauspe G., Biron K.K., Waters D.J., Straus S.E., Ostrove J.M. J. Gen. Virol. 69:2585-2593(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Molecular analysis of the thymidine kinase gene of thymidine kinase-deficient mutants of varicella-zoster virus." Mori H., Shiraki K., Kato T., Hayakawa Y., Yamanishi K., Takahashi M. Intervirology 29:301-310(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Analysis of mutations in the thymidine kinase genes of drug-resistant varicella-zoster virus populations using the polymerase chain reaction." Lacey S.F., Suzutani T., Powell K.L., Purifoy D.J., Honess R.W. J. Gen. Virol. 72:623-630(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 9883 and YS.
[4]	"Comparison of the complete DNA sequences of the Oka varicella vaccine and its parental virus." Gomi Y., Sunamachi H., Mori Y., Nagaike K., Takahashi M., Yamanishi K. J. Virol. 76:11447-11459(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Isolate Human/Japan/P-Oka/1970 and Oka varicella vaccine Biken (V-Oka-Biken).
[5]	"Complete DNA sequences of two oka strain varicella-zoster virus genomes." Tillieux S.L., Halsey W.S., Thomas E.S., Voycik J.J., Sathe G.M., Vassilev V. J. Virol. 82:11023-11044(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Oka varicella vaccine VarilRix (V-Oka-GSK) and Oka varicella vaccine Varivax V-Oka-Merk).
[6]	"Crystal structure of varicella zoster virus thymidine kinase." Bird L.E., Ren J., Wright A., Leslie K.D., Degreve B., Balzarini J., Stammers D.K. J. Biol. Chem. 278:24680-24687(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH ADP AND BROMOVINYL-DEOXYURIDINE-MONOPHOSPHATE.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M36160 Genomic DNA. Translation: AAA45865.1.
AB009252 Genomic DNA. Translation: BAA23727.2.
AB009253 Genomic DNA. Translation: BAA23728.2.
AB097932 Genomic DNA. No translation available.
AB097933 Genomic DNA. No translation available.
DQ008354 Genomic DNA. Translation: AAY57648.1.
DQ008355 Genomic DNA. Translation: AAY57719.1.

PIR

KIBEEL. A28930.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OSN	X-ray	3.20	A/B/C/D	1-341	[»]

ProteinModelPortal

P0C0E6.

SMR

P0C0E6. Positions 8-338.

ModBase

Search...

Protein-protein interaction databases

IntAct

P0C0E6. 3 interactions.

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

EvolutionaryTrace

P0C0E6.

Entry information

Entry name

KITH_VZVO

Accession

Primary (citable) accession number: P0C0E6
Secondary accession number(s): O57298, P14344, Q4JQT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	September 13, 2005
Last modified:	April 3, 2013
This is version 30 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program