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Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed-Annotation score: -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

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.

Catalytic activityi

ATP + thymidine = ADP + thymidine 5'-phosphate.UniRule annotation1 Publication

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

Keywordsi

Molecular functionKinase, Transferase
Biological processDNA synthesis
LigandATP-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 17) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10299 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000009294 Componenti: Genome

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

DrugBankiDB02921 (South)-Methanocarba-Thymidine
DB03804 5-Bromothienyldeoxyuridine
DB03312 5-Bromovinyldeoxyuridine
DB02324 5-Iodo-2'-Deoxyuridine-5'-Monophosphate
DB02500 6-(Dihydroxy-Isobutyl)-Thymine
DB04139 6-Hydroxypropylthymine
DB02495 9-(4-hydroxybutyl)-N2-phenylguanine
DB00787 Aciclovir
DB04485 Deoxythymidine
DB01004 Ganciclovir
DB03280 P1-(5'-Adenosyl)P5-(5'-Thymidyl)Pentaphosphate
DB01643 Thymidine-5'-Phosphate

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001750691 – 376Thymidine kinaseAdd BLAST376

Proteomic databases

PRIDEiP03176

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.UniRule annotation1 Publication

Structurei

Secondary structure

1376
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi48 – 54Combined sources7
Beta strandi56 – 61Combined sources6
Helixi62 – 69Combined sources8
Helixi70 – 72Combined sources3
Turni75 – 77Combined sources3
Beta strandi78 – 81Combined sources4
Helixi85 – 89Combined sources5
Beta strandi92 – 94Combined sources3
Helixi96 – 108Combined sources13
Helixi114 – 139Combined sources26
Helixi140 – 142Combined sources3
Beta strandi143 – 148Combined sources6
Beta strandi150 – 152Combined sources3
Beta strandi156 – 162Combined sources7
Helixi165 – 169Combined sources5
Helixi171 – 178Combined sources8
Helixi184 – 192Combined sources9
Beta strandi202 – 207Combined sources6
Helixi210 – 219Combined sources10
Turni222 – 224Combined sources3
Helixi229 – 250Combined sources22
Helixi255 – 258Combined sources4
Helixi259 – 262Combined sources4
Beta strandi276 – 278Combined sources3
Helixi284 – 286Combined sources3
Helixi288 – 292Combined sources5
Helixi295 – 297Combined sources3
Beta strandi302 – 304Combined sources3
Helixi306 – 320Combined sources15
Beta strandi323 – 328Combined sources6
Helixi333 – 343Combined sources11
Helixi344 – 346Combined sources3
Beta strandi349 – 354Combined sources6
Helixi357 – 372Combined sources16

3D structure databases

DisProtiDP00419
ProteinModelPortaliP03176
SMRiP03176
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03176

Family & Domainsi

Sequence similaritiesi

Belongs to the herpesviridae thymidine kinase family.UniRule annotation

Phylogenomic databases

OrthoDBiVOG0900004C

Family and domain databases

HAMAPiMF_04029 HSV_KITH, 1 hit
InterProiView protein in InterPro
IPR001889 Herpes_TK
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00693 Herpes_TK, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit

Sequencei

Sequence statusi: Complete.

P03176-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASYPCHQHA SAFDQAARSR GHNNRRTALR 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
CGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
310 320 330 340 350
NGDLYNVFAW ALDVLAKRLR SMHVFILDYD QSPAGCRDAL LQLTSGMVQT
360 370
HVTTPGSIPT ICDLARTFAR EMGEAN
Length:376
Mass (Da):40,972
Last modified:July 15, 1998 - v4
Checksum:i7E58BB575143B328
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti265T → A in CAA32315 (PubMed:2839594).Curated1
Sequence conflicti321S → P in CAA32315 (PubMed:2839594).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti6C → G. 1
Natural varianti23N → S. 1
Natural varianti36E → K. 1
Natural varianti42P → L. 1
Natural varianti251C → G. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00470 Genomic DNA Translation: CAA23742.1
X14112 Genomic DNA Translation: CAA32315.1
PIRiE30084 KIBE17
RefSeqiYP_009137097.1, NC_001806.2

Genome annotation databases

GeneIDi24271467
KEGGivg:24271467

Similar proteinsi

Entry informationi

Entry nameiKITH_HHV11
AccessioniPrimary (citable) accession number: P03176
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 15, 1998
Last modified: July 18, 2018
This is version 118 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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