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Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi

Functioni

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 viral DNA replication. Allows the virus to be reactivated and to grow in non-proliferative cells lacking a high concentration of phosphorylated nucleic acid precursors.UniRule annotation

Catalytic activityi

ATP + thymidine = ADP + thymidine 5'-phosphate.UniRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei84 – 841Proton acceptorUniRule annotation
Binding sitei102 – 1021SubstrateUniRule annotation
Binding sitei126 – 1261SubstrateUniRule annotation
Binding sitei217 – 2171ATPUniRule annotation
Binding sitei223 – 2231SubstrateUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi56 – 638ATPUniRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

DNA synthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinaseUniRule annotation (EC:2.7.1.21UniRule annotation)
Gene namesi
Name:TKUniRule annotation
Ordered Locus Names:UL23
OrganismiHuman herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2)
Taxonomic identifieri10315 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000001874 Componenti: Genome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 376376Thymidine kinasePRO_0000385457Add
BLAST

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.UniRule annotation

Structurei

3D structure databases

ProteinModelPortaliP89446.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the herpesviridae thymidine kinase family.UniRule annotation

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_04029. HSV_KITH. 1 hit.
InterProiIPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00693. Herpes_TK. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequencei

Sequence statusi: Complete.

P89446-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASHAGQQHA PAFGQAARAS GPTDGRAASR PSHRQGASGA RGDPELPTLL
60 70 80 90 100
RVYIDGPHGV GKTTTSAQLM EALGPRDNIV YVPEPMTYWQ VLGASETLTN
110 120 130 140 150
IYNTQHRLDR GEISAGEAAV VMTSAQITMS TPYAATDAVL APHIGGEAVG
160 170 180 190 200
PQAPPPALTL VFDRHPIASL LCYPAARYLM GSMTPQAVLA FVALMPPTAP
210 220 230 240 250
GTNLVLGVLP EAEHADRLAR RQRPGERLDL AMLSAIRRVY DLLANTVRYL
260 270 280 290 300
QRGGRWREDW GRLTGVAAAT PRPDPEDGAG SLPRIEDTLF ALFRVPELLA
310 320 330 340 350
PNGDLYHIFA WVLDVLADRL LPMHLFVLDY DQSPVGCRDA LLRLTAGMIP
360 370
TRVTTAGSIA EIRDLARTFA REVGGV
Length:376
Mass (Da):40,395
Last modified:May 1, 1997 - v1
Checksum:iE70AE9F26E226A44
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z86099 Genomic DNA. Translation: CAB06747.1.
RefSeqiYP_009137174.1. NC_001798.2.

Genome annotation databases

GeneIDi1487307.
KEGGivg:1487307.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z86099 Genomic DNA. Translation: CAB06747.1.
RefSeqiYP_009137174.1. NC_001798.2.

3D structure databases

ProteinModelPortaliP89446.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1487307.
KEGGivg:1487307.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_04029. HSV_KITH. 1 hit.
InterProiIPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00693. Herpes_TK. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKITH_HHV2H
AccessioniPrimary (citable) accession number: P89446
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 22, 2009
Last sequence update: May 1, 1997
Last modified: July 6, 2016
This is version 69 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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).By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.