P03177 (KITH_EBVB9) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine kinase
EC=2.7.1.21

Gene names

Name:	TK
ORF Names:	BXLF1

Organism

Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) [Reference proteome]

Taxonomic identifier

10377 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Gammaherpesvirinae › Lymphocryptovirus › Epstein-Barr virus (strain GD1)

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	607 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 memory B-cells that do not replicate their genome. Catalyzes the transfer of the gamma-phospho group of ATP to thymidine to generate dTMP in the salvage pathway of pyrimidine synthesis. The dTMP serves as a substrate for DNA polymerase during DNA replication By similarity.
Catalytic activity	ATP + thymidine = ADP + thymidine 5'-phosphate.
Subunit structure	Homodimer By similarity.
Subcellular location	Virion tegument. Host nucleus. Note: Localizes to the centrosome and more precisely to the periphery of the centriole, tightly encircling the tubulin-rich centrioles. Ref.4 Ref.5
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.
Sequence similarities	Belongs to the herpesviruses thymidine kinase family.

Ontologies

Keywords
Biological process	DNA synthesis
Cellular component	Host nucleus Virion Virion tegument
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
Cellular_component	host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell viral tegument Inferred from electronic annotation. Source: UniProtKB-SubCell
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 – 607	607	Thymidine kinase		PRO_0000175059
Regions
	Nucleotide binding	291 – 298	8	ATP By similarity
Sites
	Active site	317	1	Proton acceptor Potential
	Binding site	355	1	Substrate By similarity
	Binding site	402	1	Substrate By similarity
	Binding site	445	1	ATP By similarity

Sequences

	Sequence		Length	Mass (Da)
	P03177 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 97A4CCDB598A09F1	FASTA	607	67,193
	10 20 30 40 50 60 MAGFPGKEAG PPGGWRKCQE DESPENERHE NFYAEIDDFA PSVLTPTGSD SGAGEEDDDG 70 80 90 100 110 120 LYQVPTHWPP LMAPTGLSGE RVPCRTQAAV TSNTGNSPGS RHTSCPFTLP RGAQPPAPAH 130 140 150 160 170 180 QKPTAPTPKP RSRECGPSKT PDPFSWFRKT SCTEGGADST SRSFMYQKGF EEGLAGLGLD 190 200 210 220 230 240 DKSDCESEDE SNFRRPSSHS ALKQKNGGKG KPSGLFEHLA AHGREFSKLS KHAAQLKRLS 250 260 270 280 290 300 GSVMNVLNLD DAQDTRQAKA QRKESMRVPI VTHLTNHVPV IKPACSLFLE GAPGVGKTTM 310 320 330 340 350 360 LNHLKAVFGD LTIVVPEPMR YWTHVYENAI KAMHKNVTRA RHGREDTSAE VLACQMKFTT 370 380 390 400 410 420 PFRVLASRKR SLLVTESGAR SVAPLDCWIL HDRHLLSASV VFPLMLLRSQ LLSYSDFIQV 430 440 450 460 470 480 LATFTADPGD TIVWMKLNVE ENMRRLKKRG RKHESGLDAG YLKSVNDAYH AVYCAWLLTQ 490 500 510 520 530 540 YFAPEDIVKV CAGLTTITTV CHQSHTPIIR SGVAEKLYKN SIFSVLKEVI QPFRADAVLL 550 560 570 580 590 600 EVCLAFTRTL AYLQFVLVDL SEFQDDLPGC WTEIYMQALK NPAIRSQFFD WAGLSKVISD FERGNRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence analysis of the 17,166 base-pair EcoRI fragment C of B95-8 Epstein-Barr virus." Bankier A.T., Deininger P.L., Farrell P.J., Barrell B.G. Mol. Biol. Med. 1:21-45(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"DNA sequence and expression of the B95-8 Epstein-Barr virus genome." Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J., Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C., Tuffnell P.S., Barrell B.G. Nature 310:207-211(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Identification of an Epstein-Barr virus-coded thymidine kinase." Littler E., Zeuthen J., McBride A.A., Soerensen E.T., Powell K.L., Walsh-Arrand J.E., Arrand J.R. EMBO J. 5:1959-1966(1986) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF PROTEIN.
[4]	"Proteins of purified Epstein-Barr virus." Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E., Illanes D., Sarracino D., Kieff E. Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"Epstein-Barr virus thymidine kinase is a centrosomal resident precisely localized to the periphery of centrioles." Gill M.B., Kutok J.L., Fingeroth J.D. J. Virol. 81:6523-6535(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	V01555 Genomic DNA. Translation: CAA24799.1. AJ507799 Genomic DNA. Translation: CAD53451.1.
PIR	KIBETE. A00615.
RefSeq	YP_401701.1. NC_007605.1.
3D structure databases
ProteinModelPortal	P03177.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	3783741.
Phylogenomic databases
ProtClustDB	PHA3132.
Enzyme and pathway databases
SABIO-RK	P03177.
Family and domain databases
InterPro	IPR001889. Herpes_TK. IPR013672. Herpes_TK_C. [Graphical view]
Pfam	PF00693. Herpes_TK. 1 hit. PF08465. Herpes_TK_C. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

KITH_EBVB9

Accession

Primary (citable) accession number: P03177
Secondary accession number(s): Q777B9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 1, 1995
Last modified:	April 3, 2013
This is version 65 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program