P09250 (KITH_VZVD) 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 Dumas) (HHV-3) (Human herpesvirus 3) [Reference proteome]

Taxonomic identifier

10338 [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	Inferred from homology

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	Complete proteome Reference 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_0000175084
Regions
	Nucleotide binding	19 – 26	8	ATP Potential
Sites
	Active site	48	1	Proton acceptor Potential
	Binding site	66	1	Substrate By similarity
	Binding site	90	1	Substrate By similarity
	Binding site	139	1	Substrate By similarity
	Binding site	183	1	ATP By similarity
Natural variations
	Natural variant	130	1	R → Q in strain: Isolate 7-1-3.
	Natural variant	154	1	L → P in strain: Isolate 40a2.
	Natural variant	288	1	S → L in strain: Ellen, ppIIa, Isolate clinical GK, Isolate 7-1-3, Isolate 101 and Isolate 3-5-2/KB3.
	Natural variant	319	1	A → V in strain: Isolate clinical GK.

Sequences

	Sequence		Length	Mass (Da)
	P09250 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 1C95CC39750B0C07	FASTA	341	37,817
	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 METLSNCSRS MSPFVLSLEQ 310 320 330 340 TPQHAAQELK TLLPQMTPAN MSSGAWNILK ELVNAVQDNT S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete DNA sequence of varicella-zoster virus." Davison A.J., Scott J.E. J. Gen. Virol. 67:1759-1816(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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]. Strain: Ellen, Isolate 101, Isolate 3-5-2/KB3, Isolate 40a2, Isolate 7-1-3, isolate clinical GK and ppIIa.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04370 Genomic DNA. Translation: CAA27919.1.
PIR	KIBE36. A27341. KIBEEL. A28930. KIBE73. B28930. KIBEGK. E28930.
3D structure databases
ProteinModelPortal	P09250.
SMR	P09250. Positions 8-338.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
ProtClustDB	PHA3138.
Family and domain databases
InterPro	IPR001889. Herpes_TK. [Graphical view]
Pfam	PF00693. Herpes_TK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P09250.
ChEMBL	CHEMBL4784.
DrugBank	DB00194. Vidarabine.

Entry information

Entry name

KITH_VZVD

Accession

Primary (citable) accession number: P09250
Secondary accession number(s): O57298 , P0C0E5, P0C0E7, P14341, P14342, P14343, P14344

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	April 3, 2013
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program