Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (strain SC16) (HHV-1) (Human herpes simplex virus 1)
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)DescriptionActionsGraphical viewLength
Active sitei83Proton acceptorUniRule annotation1
Binding sitei101SubstrateUniRule annotation1
Binding sitei125SubstrateUniRule annotation1
Binding sitei216ATPUniRule annotation1
Binding sitei222SubstrateUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi56 – 63ATPUniRule annotation8

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 1 (strain SC16) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10309 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Pathology & Biotechi

Biotechnological usei

Used in molecular biology as a selectable marker to identify transfected eukaryotic cells. Used in cancer suicide gene therapy to selectively kill transformed cells.

Chemistry databases

ChEMBLiCHEMBL1820.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001750731 – 376Thymidine kinaseAdd BLAST376

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.UniRule annotation

Chemistry databases

BindingDBiP06479.

Structurei

3D structure databases

ProteinModelPortaliP06479.
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.

P06479-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASYPGHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RPEQKMPTLL
60 70 80 90 100
RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWRV LGASETIANI
110 120 130 140 150
YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS
160 170 180 190 200
HAPPPALTLI FDRHPIAALL CYPAARYLMG SMTPQAVLAF VALIPPTLPG
210 220 230 240 250
TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG LLANTVRYLQ
260 270 280 290 300
GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
310 320 330 340 350
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMIQT
360 370
HVTTPGSIPT ICDLARTFAR EMGEAN
Length:376
Mass (Da):40,877
Last modified:November 1, 1988 - v1
Checksum:i5B661B145585125A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03764 Genomic DNA. Translation: CAA27395.1.
PIRiA27240. KIBE16.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03764 Genomic DNA. Translation: CAA27395.1.
PIRiA27240. KIBE16.

3D structure databases

ProteinModelPortaliP06479.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiP06479.
ChEMBLiCHEMBL1820.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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_HHV1S
AccessioniPrimary (citable) accession number: P06479
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 1, 1988
Last modified: October 5, 2016
This is version 65 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.

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.