P06478 (KITH_HHV1C) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine kinase
EC=2.7.1.21

Gene names

Name:	TK
Synonyms:	UL23

Organism

Human herpesvirus 1 (strain CL101) (HHV-1) (Human herpes simplex virus 1)

Taxonomic identifier

10302 [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 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 herpesviruses thymidine kinase family.

Ontologies

Keywords
Biological process	DNA synthesis
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_0000175070
Regions
	Nucleotide binding	56 – 63	8	ATP By similarity
Sites
	Active site	83	1	Proton acceptor Potential
	Binding site	101	1	Substrate By similarity
	Binding site	125	1	Substrate By similarity
	Binding site	172	1	Substrate By similarity
	Binding site	216	1	ATP By similarity

Sequences

	Sequence		Length	Mass (Da)
	P06478 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: FFBAF5DC0B13D151	FASTA	376	40,913
	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 PHVGGEAGSS HAPPPALTLI FDRHPIAALL CYPAARYLMG 190 200 210 220 230 240 SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG 250 260 270 280 290 300 LLANTVRYLQ GGGSWWEDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 310 320 330 340 350 360 NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT HVTTPGSIPT 370 ICDLARTFAR EMGEAN

References

[1]	"Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1." Wagner M.J., Sharp J.A., Summers W.C. Proc. Natl. Acad. Sci. U.S.A. 78:1441-1445(1981) [PubMed: 6262799] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02224 Genomic DNA. Translation: AAA45811.1. V00467 Genomic DNA. Translation: CAA23741.1.
PIR	KIBETC. A93870.
3D structure databases
ProteinModelPortal	P06478.
SMR	P06478. 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	DB00299. Penciclovir.

Entry information

Entry name

KITH_HHV1C

Accession

Primary (citable) accession number: P06478

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	November 30, 2010
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program