P04407 (KITH_HHV23) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine kinase
EC=2.7.1.21

Gene names

Name:

TK

Organism

Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2)

Taxonomic identifier

10313 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 2

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_0000175074
Regions
	Nucleotide binding	56 – 63	8	ATP By similarity
Sites
	Active site	84	1	Proton acceptor Potential
	Binding site	102	1	Substrate By similarity
	Binding site	126	1	Substrate By similarity
	Binding site	173	1	Substrate By similarity
	Binding site	217	1	ATP By similarity
Experimental info
	Sequence conflict	271	1	Missing in CAA25858. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P04407 [UniParc]. Last modified December 15, 1998. Version 2. Checksum: 0B1D68B0BBA3C8A5	FASTA	376	40,467
	10 20 30 40 50 60 MASHAGQQHA PAFGQAARAS GPTDGRAASR PSHRQGASEA RGDPELPTLL RVYIDGPHGV 70 80 90 100 110 120 GKTTTSAQLM EALGPRDNIV YVPEPMTYWQ VLGASETLTN IYNTQHRLDR GEISAGEAAV 130 140 150 160 170 180 VMTSAQITMS TPYAATDAVL APHIGGEAVG PQAPPPALTL VFDRHPIASL LCYPAARYLM 190 200 210 220 230 240 GSMTPQAVLA FVALMPPTAP GTNLVLGVLP EAEHADRLAR RQRPGERLDL AMLSAIRRVY 250 260 270 280 290 300 DLLANTVRYL QRGGRWREDW GRLTGVAAAT PRPDPEDGAG SLPRIEDTLF ALFRVPELLA 310 320 330 340 350 360 PNGDLYHIFA WVLDVLADRL LPMHLFVLDY DQSPVGCRDA LLRLTAGMIP TRVTTAGSIA 370 EIRDLARTFA REVGGV

References

[1]	"Nucleotide sequence of the herpes simplex virus type 2 (HSV-2) thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide and its comparison with the HSV-1 thymidine kinase gene." Kit S., Kit M., Qavi H., Trkula D., Otsuka H. Biochim. Biophys. Acta 741:158-170(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Nucleotide sequence of the herpes simplex virus type 2 thymidine kinase gene." Swain M.A., Galloway D.A. J. Virol. 46:1045-1050(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Nucleotide sequence changes in thymidine kinase gene of herpes simplex virus type 2 clones from an isolate of a patient treated with acyclovir." Kit S., Sheppard M., Ichimura H., Nusinoff-Lehrman S., Ellis M.N., Fyfe J.A., Otsuka H. Antimicrob. Agents Chemother. 31:1483-1490(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	X01712 Genomic DNA. Translation: CAA25858.1. V00466 Genomic DNA. Translation: CAA23740.1. M29942 Genomic DNA. Translation: AAA45856.1.
PIR	KIBET3. A90648.
3D structure databases
ProteinModelPortal	P04407.
SMR	P04407. Positions 46-374.
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
BindingDB	P04407.

Entry information

Entry name

KITH_HHV23

Accession

Primary (citable) accession number: P04407

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	December 15, 1998
Last modified:	April 3, 2013
This is version 59 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program