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Protein

Thymidine kinase

Gene

TK

Organism
Varicella-zoster virus (strain Oka vaccine) (HHV-3) (Human herpesvirus 3)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

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 sitei48 – 481Proton acceptorUniRule annotation
Binding sitei66 – 661SubstrateUniRule annotation
Binding sitei90 – 901SubstrateUniRule annotation
Binding sitei183 – 1831ATPUniRule annotation
Binding sitei189 – 1891SubstrateUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi19 – 268ATPUniRule 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:ORF36
OrganismiVaricella-zoster virus (strain Oka vaccine) (HHV-3) (Human herpesvirus 3)
Taxonomic identifieri341980 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeVaricellovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000008505 Componenti: Genome
  • UP000008504 Componenti: Genome
  • UP000002603 Componenti: Genome
  • UP000008506 Componenti: Genome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 341341Thymidine kinasePRO_0000175087Add
BLAST

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.UniRule annotation

Protein-protein interaction databases

IntActiP0C0E6. 3 interactions.

Structurei

Secondary structure

1
341
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi10 – 2314Combined sources
Helixi27 – 348Combined sources
Turni35 – 384Combined sources
Helixi40 – 423Combined sources
Beta strandi43 – 464Combined sources
Helixi50 – 534Combined sources
Helixi61 – 7313Combined sources
Helixi79 – 9214Combined sources
Helixi94 – 10613Combined sources
Beta strandi124 – 1307Combined sources
Helixi133 – 1364Combined sources
Helixi138 – 1458Combined sources
Helixi151 – 1533Combined sources
Helixi154 – 1585Combined sources
Beta strandi169 – 1746Combined sources
Helixi177 – 1837Combined sources
Helixi196 – 21823Combined sources
Helixi224 – 2274Combined sources
Helixi233 – 2397Combined sources
Helixi253 – 2553Combined sources
Helixi258 – 2614Combined sources
Helixi264 – 2663Combined sources
Helixi275 – 29016Combined sources
Beta strandi292 – 2976Combined sources
Helixi302 – 31211Combined sources
Helixi313 – 3153Combined sources
Beta strandi319 – 3213Combined sources
Helixi323 – 33614Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1OSNX-ray3.20A/B/C/D1-341[»]
ProteinModelPortaliP0C0E6.
SMRiP0C0E6. Positions 8-338.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0C0E6.

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.

P0C0E6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTDKTDVKM GVLRIYLDGA YGIGKTTAAE EFLHHFAITP NRILLIGEPL
60 70 80 90 100
SYWRNLAGED AICGIYGTQT RRLNGDVSPE DAQRLTAHFQ SLFCSPHAIM
110 120 130 140 150
HAKISALMDT STSDLVQVNK EPYKIMLSDR HPIASTICFP LSRYLVGDMS
160 170 180 190 200
PAALPGLLFT LPAEPPGTNL VVCTVSLPSH LSRVSKRARP GETVNLPFVM
210 220 230 240 250
VLRNVYIMLI NTIIFLKTNN WHAGWNTLSF CNDVFKQKLQ KSECIKLREV
260 270 280 290 300
PGIEDTLFAV LKLPELCGEF GNILPLWAWG METLSNCLRS MSPFVLSLEQ
310 320 330 340
TPQHAAQELK TLLPQMTPAN MSSGAWNILK ELVNAVQDNT S
Length:341
Mass (Da):37,843
Last modified:September 13, 2005 - v1
Checksum:iF38ACC39751C076A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36160 Genomic DNA. Translation: AAA45865.1.
AB009252 Genomic DNA. Translation: BAA23727.2.
AB009253 Genomic DNA. Translation: BAA23728.2.
AB097932 Genomic DNA. No translation available.
AB097933 Genomic DNA. No translation available.
DQ008354 Genomic DNA. Translation: AAY57648.1.
DQ008355 Genomic DNA. Translation: AAY57719.1.
PIRiA28930. KIBEEL.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36160 Genomic DNA. Translation: AAA45865.1.
AB009252 Genomic DNA. Translation: BAA23727.2.
AB009253 Genomic DNA. Translation: BAA23728.2.
AB097932 Genomic DNA. No translation available.
AB097933 Genomic DNA. No translation available.
DQ008354 Genomic DNA. Translation: AAY57648.1.
DQ008355 Genomic DNA. Translation: AAY57719.1.
PIRiA28930. KIBEEL.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1OSNX-ray3.20A/B/C/D1-341[»]
ProteinModelPortaliP0C0E6.
SMRiP0C0E6. Positions 8-338.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP0C0E6. 3 interactions.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP0C0E6.

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_VZVO
AccessioniPrimary (citable) accession number: P0C0E6
Secondary accession number(s): O57298, P14344, Q4JQT9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: September 13, 2005
Last modified: September 7, 2016
This is version 42 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

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.