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P06479

- KITH_HHV1S

UniProt

P06479 - KITH_HHV1S

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Protein
Thymidine kinase
Gene
TK, UL23
Organism
Human herpesvirus 1 (strain SC16) (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 acceptor Reviewed prediction
Binding sitei101 – 1011Substrate By similarity
Binding sitei125 – 1251Substrate By similarity
Binding sitei172 – 1721Substrate By similarity
Binding sitei216 – 2161ATP By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi56 – 638ATP By 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

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinase (EC:2.7.1.21)
Gene namesi
Name:TK
Synonyms: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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 376376Thymidine kinase
PRO_0000175073Add
BLAST

Interactioni

Subunit structurei

Homodimer By similarity.

Structurei

3D structure databases

ProteinModelPortaliP06479.
SMRiP06479. Positions 46-376.

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.

P06479-1 [UniParc]FASTAAdd to Basket

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MASYPGHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RPEQKMPTLL    50
RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY VPEPMTYWRV LGASETIANI 100
YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS 150
HAPPPALTLI FDRHPIAALL CYPAARYLMG SMTPQAVLAF VALIPPTLPG 200
TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG LLANTVRYLQ 250
GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP 300
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMIQT 350
HVTTPGSIPT ICDLARTFAR EMGEAN 376
Length:376
Mass (Da):40,877
Last modified:November 1, 1988 - v1
Checksum:i5B661B145585125A
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X03764 Genomic DNA. Translation: CAA27395.1.
PIRiA27240. KIBE16.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X03764 Genomic DNA. Translation: CAA27395.1 .
PIRi A27240. KIBE16.

3D structure databases

ProteinModelPortali P06479.
SMRi P06479. Positions 46-376.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P06479.
ChEMBLi CHEMBL1820.

Protocols and materials databases

Structural Biology Knowledgebase Search...

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. "Evidence that the 'active centre' of the herpes simplex virus thymidine kinase involves an interaction between three distinct regions of the polypeptide."
    Darby G., Larder B.A., Inglis M.M.
    J. Gen. Virol. 67:753-758(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

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: April 16, 2014
This is version 59 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

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