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P03176

- KITH_HHV11

UniProt

P03176 - KITH_HHV11

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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: 4 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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei83 – 831Proton acceptorSequence Analysis
Binding sitei101 – 1011Substrate
Binding sitei125 – 1251Substrate
Binding sitei216 – 2161ATP
Binding sitei222 – 2221Substrate

Regions

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

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

BRENDAi2.7.1.21. 2649.
SABIO-RKP03176.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidine kinase (EC:2.7.1.21)
Gene namesi
Name:TK
ORF 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]
ProteomesiUP000009294: 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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 376376Thymidine kinasePRO_0000175069Add
BLAST

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

1
376
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi48 – 547Combined sources
Beta strandi56 – 616Combined sources
Helixi62 – 698Combined sources
Helixi70 – 723Combined sources
Turni75 – 773Combined sources
Beta strandi78 – 814Combined sources
Helixi85 – 895Combined sources
Beta strandi92 – 943Combined sources
Helixi96 – 10813Combined sources
Helixi114 – 13926Combined sources
Helixi140 – 1423Combined sources
Beta strandi143 – 1486Combined sources
Beta strandi150 – 1523Combined sources
Beta strandi156 – 1627Combined sources
Helixi165 – 1695Combined sources
Helixi171 – 1788Combined sources
Helixi184 – 1929Combined sources
Beta strandi202 – 2076Combined sources
Helixi210 – 21910Combined sources
Turni222 – 2243Combined sources
Helixi229 – 25022Combined sources
Helixi255 – 2584Combined sources
Helixi259 – 2624Combined sources
Beta strandi276 – 2805Combined sources
Helixi284 – 2863Combined sources
Helixi288 – 2925Combined sources
Helixi295 – 2973Combined sources
Beta strandi302 – 3043Combined sources
Helixi306 – 32015Combined sources
Beta strandi323 – 3286Combined sources
Helixi333 – 34311Combined sources
Helixi344 – 3463Combined sources
Beta strandi349 – 3546Combined sources
Helixi357 – 37216Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E2HX-ray1.90A/B46-376[»]
1E2IX-ray1.90A/B46-376[»]
1E2JX-ray2.50A/B46-376[»]
1E2KX-ray1.70A/B46-376[»]
1E2LX-ray2.40A/B46-376[»]
1E2MX-ray2.20A/B46-376[»]
1E2NX-ray2.20A/B46-376[»]
1E2PX-ray2.50A/B46-376[»]
1KI2X-ray2.20A/B46-376[»]
1KI3X-ray2.37A/B46-376[»]
1KI4X-ray2.34A/B46-376[»]
1KI6X-ray2.37A/B46-376[»]
1KI7X-ray2.20A/B46-376[»]
1KI8X-ray2.20A/B46-376[»]
1KIMX-ray2.14A/B11-376[»]
1OF1X-ray1.95A/B1-376[»]
1P7CX-ray2.10A/B34-376[»]
1QHIX-ray1.90A/B11-376[»]
1VTKX-ray2.75A34-376[»]
2KI5X-ray1.90A/B11-376[»]
2VTKX-ray2.80A34-376[»]
3F0TX-ray2.00A/B45-376[»]
3RDPX-ray2.80A/B46-376[»]
3VTKX-ray3.00A34-376[»]
4IVPX-ray2.10A/B46-376[»]
4IVQX-ray1.90A/B46-376[»]
4IVRX-ray2.40A/B46-376[»]
4JBXX-ray2.10A/B45-376[»]
4JBYX-ray2.00A/B45-376[»]
4OQLX-ray2.10A/B45-376[»]
4OQMX-ray2.20A/B45-376[»]
4OQNX-ray2.30A/B45-376[»]
4OQXX-ray2.50A/B45-376[»]
DisProtiDP00419.
ProteinModelPortaliP03176.
SMRiP03176. Positions 46-376.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03176.

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti265 – 2651T → A in CAA32315. (PubMed:2839594)Curated
Sequence conflicti321 – 3211S → P in CAA32315. (PubMed:2839594)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61C → G.
Natural varianti23 – 231N → S.
Natural varianti36 – 361E → K.
Natural varianti42 – 421P → L.
Natural varianti251 – 2511C → G.

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.
RefSeqiNP_044624.1. NC_001806.1.

Genome annotation databases

GeneIDi2703374.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00470 Genomic DNA. Translation: CAA23742.1 .
X14112 Genomic DNA. Translation: CAA32315.1 .
PIRi E30084. KIBE17.
RefSeqi NP_044624.1. NC_001806.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1E2H X-ray 1.90 A/B 46-376 [» ]
1E2I X-ray 1.90 A/B 46-376 [» ]
1E2J X-ray 2.50 A/B 46-376 [» ]
1E2K X-ray 1.70 A/B 46-376 [» ]
1E2L X-ray 2.40 A/B 46-376 [» ]
1E2M X-ray 2.20 A/B 46-376 [» ]
1E2N X-ray 2.20 A/B 46-376 [» ]
1E2P X-ray 2.50 A/B 46-376 [» ]
1KI2 X-ray 2.20 A/B 46-376 [» ]
1KI3 X-ray 2.37 A/B 46-376 [» ]
1KI4 X-ray 2.34 A/B 46-376 [» ]
1KI6 X-ray 2.37 A/B 46-376 [» ]
1KI7 X-ray 2.20 A/B 46-376 [» ]
1KI8 X-ray 2.20 A/B 46-376 [» ]
1KIM X-ray 2.14 A/B 11-376 [» ]
1OF1 X-ray 1.95 A/B 1-376 [» ]
1P7C X-ray 2.10 A/B 34-376 [» ]
1QHI X-ray 1.90 A/B 11-376 [» ]
1VTK X-ray 2.75 A 34-376 [» ]
2KI5 X-ray 1.90 A/B 11-376 [» ]
2VTK X-ray 2.80 A 34-376 [» ]
3F0T X-ray 2.00 A/B 45-376 [» ]
3RDP X-ray 2.80 A/B 46-376 [» ]
3VTK X-ray 3.00 A 34-376 [» ]
4IVP X-ray 2.10 A/B 46-376 [» ]
4IVQ X-ray 1.90 A/B 46-376 [» ]
4IVR X-ray 2.40 A/B 46-376 [» ]
4JBX X-ray 2.10 A/B 45-376 [» ]
4JBY X-ray 2.00 A/B 45-376 [» ]
4OQL X-ray 2.10 A/B 45-376 [» ]
4OQM X-ray 2.20 A/B 45-376 [» ]
4OQN X-ray 2.30 A/B 45-376 [» ]
4OQX X-ray 2.50 A/B 45-376 [» ]
DisProti DP00419.
ProteinModelPortali P03176.
SMRi P03176. Positions 46-376.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P03176.
DrugBanki DB00787. Aciclovir.
DB01004. Ganciclovir.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 2703374.

Enzyme and pathway databases

BRENDAi 2.7.1.21. 2649.
SABIO-RK P03176.

Miscellaneous databases

EvolutionaryTracei P03176.

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

« Hide 'large scale' publications
  1. "The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene."
    McKnight S.L.
    Nucleic Acids Res. 8:5949-5964(1980) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1."
    McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P.
    J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The three-dimensional structure of thymidine kinase from herpes simplex virus type 1."
    Wild K., Bohner T., Aubry A., Folkers G., Schulz G.E.
    FEBS Lett. 368:289-292(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-376.
  4. "Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir."
    Brown D.G., Visse R., Sandhu G., Davies A., Rizkallah P.J., Melitz C., Summers W.C., Sanderson M.R.
    Nat. Struct. Biol. 2:876-881(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
  5. "The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue."
    Wild K., Bohner T., Folkers G., Schulz G.E.
    Protein Sci. 6:2097-2106(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 34-376.
  6. "Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands."
    Champness J.N., Bennett M.S., Wien F., Visse R., Summers W.C., Herdewijn P., de Clerq E., Ostrowski T., Jarvest R.L., Sanderson M.R.
    Proteins 32:350-361(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
  7. "Structure to 1.9-A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir."
    Bennett M.S., Wien F., Champness J.N., Batuwangala T., Rutherford T., Summers W.C., Sun H., Wright G., Sanderson M.R.
    FEBS Lett. 443:121-125(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
  8. "Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography."
    Vogt J., Perozzo R., Pautsch A., Prota A., Schelling P., Pilger B., Folkers G., Scapozza L., Schulz G.E.
    Proteins 41:545-553(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 45-376 IN COMPLEX WITH ADENINE ANALOG, CATALYTIC ACTIVITY, SUBUNIT.

Entry informationi

Entry nameiKITH_HHV11
AccessioniPrimary (citable) accession number: P03176
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 15, 1998
Last modified: November 26, 2014
This is version 101 of the entry and version 4 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.

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

External Data

Dasty 3