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P08333

- KITH_HHV1E

UniProt

P08333 - KITH_HHV1E

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Protein

Thymidine kinase

Gene

TK

Organism
Human herpesvirus 1 (strain HFEM) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli

Functioni

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 activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei83 – 831Proton acceptorSequence Analysis
Binding sitei101 – 1011SubstrateBy similarity
Binding sitei125 – 1251SubstrateBy similarity
Binding sitei172 – 1721SubstrateBy similarity
Binding sitei216 – 2161ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi56 – 638ATPBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. thymidine kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. DNA replication Source: UniProtKB-KW
  2. TMP biosynthetic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

DNA synthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKP08333.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinase (EC:2.7.1.21)
Gene namesi
Name:TK
Synonyms:UL23
OrganismiHuman herpesvirus 1 (strain HFEM) (HHV-1) (Human herpes simplex virus 1)
Taxonomic identifieri10303 [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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 376376Thymidine kinasePRO_0000175071Add
BLAST

Interactioni

Subunit structurei

Homodimer.By similarity

Structurei

3D structure databases

ProteinModelPortaliP08333.
SMRiP08333. Positions 46-376.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Family and domain databases

Gene3Di3.40.50.300. 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.

P08333-1 [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 MTSAQITIGM 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):40,859
Last modified:November 1, 1988 - v1
Checksum:i5A721B145745125A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14884 Genomic DNA. Translation: AAA45814.1.
PIRiA24187. KIBEHF.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14884 Genomic DNA. Translation: AAA45814.1 .
PIRi A24187. KIBEHF.

3D structure databases

ProteinModelPortali P08333.
SMRi P08333. Positions 46-376.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

SABIO-RK P08333.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR001889. Herpes_TK.
IPR027417. P-loop_NTPase.
[Graphical view ]
Pfami PF00693. Herpes_TK. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "The properties and sequence of glycoprotein H of herpes simplex virus type 1."
    Gompels U., Minson A.
    Virology 153:230-247(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Entry informationi

Entry nameiKITH_HHV1E
AccessioniPrimary (citable) accession number: P08333
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: November 1, 1988
Last modified: October 1, 2014
This is version 62 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), 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.

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3