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Protein

Deoxynucleoside kinase

Gene

dnk

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Deoxyribonucleoside kinase that has a broad specificity phosphorylating thymidine, deoxyadenosine, deoxycytidine and deoxyguanosine. Specificity is higher for pyrimidine nucleosides. Several anti-viral and anti-cancer nucleoside analogs are also efficiently phosphorylated.3 Publications

Catalytic activityi

ATP + 2'-deoxynucleoside = ADP + 2'-deoxynucleoside 5'-phosphate.4 Publications

Enzyme regulationi

Subject to feedback inhibition by dTTP.1 Publication

Kineticsi

  1. KM=0.9 µM for thymidine2 Publications
  2. KM=1 µM for deoxycytidine2 Publications
  3. KM=109 µM for deoxyadenosine2 Publications
  4. KM=654 µM for deoxyguanosine2 Publications
  1. Vmax=29.4 mmol/min/mg enzyme with thymidine as substrate2 Publications
  2. Vmax=28.7 mmol/min/mg enzyme with deoxycytidine as substrate2 Publications
  3. Vmax=35.5 mmol/min/mg enzyme with deoxyadenosine as substrate2 Publications
  4. Vmax=37.7 mmol/min/mg enzyme with deoxyguanosine as substrate2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei52 – 521Substrate
Binding sitei70 – 701Substrate
Binding sitei81 – 811Substrate
Active sitei104 – 1041Proton acceptorSequence analysis
Binding sitei105 – 1051Substrate
Binding sitei172 – 1721Substrate

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi27 – 359ATPBy similarity

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • deoxynucleoside kinase activity Source: UniProtKB
  • kinase activity Source: FlyBase
  • thymidine kinase activity Source: FlyBase

GO - Biological processi

  • DNA biosynthetic process Source: UniProtKB-KW
  • nucleoside diphosphate phosphorylation Source: UniProtKB
  • nucleotide phosphorylation Source: FlyBase
  • phosphorylation Source: FlyBase
  • TMP biosynthetic process Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

DNA synthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-17889.
BRENDAi2.7.1.145. 1994.
ReactomeiR-DME-73614. Pyrimidine salvage reactions.
R-DME-74217. Purine salvage.
SABIO-RKQ9XZT6.

Names & Taxonomyi

Protein namesi
Recommended name:
Deoxynucleoside kinase (EC:2.7.1.145)
Alternative name(s):
Deoxyribonucleoside kinase
Short name:
Dm-dNK
Multispecific deoxynucleoside kinase
Gene namesi
Name:dnk
ORF Names:CG5452
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3R

Organism-specific databases

FlyBaseiFBgn0022338. dnk.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: FlyBase
  • mitochondrion Source: FlyBase
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi45 – 451N → D: Reduces enzyme activity towards dA, dG, dT and dC about 5-fold. 1 Publication
Mutagenesisi64 – 641N → D: Reduces enzyme activity towards dT and dC about 500-fold. Reduces enzyme activity towards dG about 3900-fold. Reduces enzyme activity towards dA about 900-fold. 1 Publication

Chemistry

ChEMBLiCHEMBL4760.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 250250Deoxynucleoside kinasePRO_0000175097Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei236 – 2361Phosphoserine1 Publication
Modified residuei241 – 2411Phosphoserine1 Publication
Modified residuei243 – 2431Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9XZT6.
PRIDEiQ9XZT6.

PTM databases

iPTMnetiQ9XZT6.

Expressioni

Gene expression databases

BgeeiQ9XZT6.
ExpressionAtlasiQ9XZT6. differential.
GenevisibleiQ9XZT6. DM.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi67276. 8 interactions.
DIPiDIP-23491N.
IntActiQ9XZT6. 1 interaction.
MINTiMINT-879155.
STRINGi7227.FBpp0302815.

Chemistry

BindingDBiQ9XZT6.

Structurei

Secondary structure

1
250
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni15 – 173Combined sources
Beta strandi21 – 288Combined sources
Helixi33 – 386Combined sources
Helixi39 – 435Combined sources
Turni44 – 463Combined sources
Beta strandi47 – 504Combined sources
Helixi54 – 574Combined sources
Beta strandi60 – 623Combined sources
Helixi65 – 717Combined sources
Helixi73 – 9321Combined sources
Beta strandi98 – 1058Combined sources
Helixi107 – 1126Combined sources
Helixi114 – 1207Combined sources
Beta strandi122 – 1243Combined sources
Helixi126 – 14217Combined sources
Beta strandi148 – 1547Combined sources
Helixi157 – 16711Combined sources
Helixi170 – 1723Combined sources
Helixi177 – 19115Combined sources
Turni192 – 1943Combined sources
Beta strandi200 – 2067Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1J90X-ray2.56A/B1-230[»]
1OE0X-ray2.40A/B/C/D1-230[»]
1OT3X-ray2.50A/B/C/D/E/F/G/H1-250[»]
1ZM7X-ray2.20A/B/C/D1-230[»]
1ZMXX-ray3.10A/B/C/D/E/F/G/H1-230[»]
2JCSX-ray2.50A/B1-230[»]
2JJ8X-ray2.80A/B/C/D1-230[»]
2VP0X-ray2.20A/B1-250[»]
2VP2X-ray2.50A/B1-230[»]
2VP4X-ray2.20A/B/C/D1-230[»]
2VP5X-ray2.30A/B1-230[»]
2VP6X-ray3.00A/B/C/D/E/F/G/H1-230[»]
2VP9X-ray2.90A/B/C/D/E/F/G/H1-230[»]
2VPPX-ray2.20A/B1-230[»]
2VQSX-ray2.90A/B/C/D1-230[»]
ProteinModelPortaliQ9XZT6.
SMRiQ9XZT6. Positions 12-210.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9XZT6.

Family & Domainsi

Sequence similaritiesi

Belongs to the DCK/DGK family.Curated

Phylogenomic databases

eggNOGiKOG4235. Eukaryota.
COG1428. LUCA.
GeneTreeiENSGT00510000046588.
InParanoidiQ9XZT6.
KOiK05961.
OMAiMYRDACR.
OrthoDBiEOG7R56T9.
PhylomeDBiQ9XZT6.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR002624. DCK/DGK.
IPR031314. DNK_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF01712. dNK. 1 hit.
[Graphical view]
PIRSFiPIRSF000705. DNK. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9XZT6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEAASCARK GTKYAEGTQP FTVLIEGNIG SGKTTYLNHF EKYKNDICLL
60 70 80 90 100
TEPVEKWRNV NGVNLLELMY KDPKKWAMPF QSYVTLTMLQ SHTAPTNKKL
110 120 130 140 150
KIMERSIFSA RYCFVENMRR NGSLEQGMYN TLEEWYKFIE ESIHVQADLI
160 170 180 190 200
IYLRTSPEVA YERIRQRARS EESCVPLKYL QELHELHEDW LIHQRRPQSC
210 220 230 240 250
KVLVLDADLN LENIGTEYQR SESSIFDAIS SNQQPSPVLV SPSKRQRVAR
Length:250
Mass (Da):29,088
Last modified:November 1, 1999 - v1
Checksum:i17C5DF197B8792DB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045610 mRNA. Translation: AAD47355.2.
AF185268 Genomic DNA. Translation: AAD56545.1.
Y18048 mRNA. Translation: CAB41881.1.
AE014297 Genomic DNA. Translation: AAF55615.1.
RefSeqiNP_001262722.1. NM_001275793.1.
NP_524399.1. NM_079675.3.
UniGeneiDm.1248.

Genome annotation databases

EnsemblMetazoaiFBtr0083707; FBpp0083121; FBgn0022338.
FBtr0321263; FBpp0302815; FBgn0022338.
GeneIDi42273.
KEGGidme:Dmel_CG5452.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045610 mRNA. Translation: AAD47355.2.
AF185268 Genomic DNA. Translation: AAD56545.1.
Y18048 mRNA. Translation: CAB41881.1.
AE014297 Genomic DNA. Translation: AAF55615.1.
RefSeqiNP_001262722.1. NM_001275793.1.
NP_524399.1. NM_079675.3.
UniGeneiDm.1248.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1J90X-ray2.56A/B1-230[»]
1OE0X-ray2.40A/B/C/D1-230[»]
1OT3X-ray2.50A/B/C/D/E/F/G/H1-250[»]
1ZM7X-ray2.20A/B/C/D1-230[»]
1ZMXX-ray3.10A/B/C/D/E/F/G/H1-230[»]
2JCSX-ray2.50A/B1-230[»]
2JJ8X-ray2.80A/B/C/D1-230[»]
2VP0X-ray2.20A/B1-250[»]
2VP2X-ray2.50A/B1-230[»]
2VP4X-ray2.20A/B/C/D1-230[»]
2VP5X-ray2.30A/B1-230[»]
2VP6X-ray3.00A/B/C/D/E/F/G/H1-230[»]
2VP9X-ray2.90A/B/C/D/E/F/G/H1-230[»]
2VPPX-ray2.20A/B1-230[»]
2VQSX-ray2.90A/B/C/D1-230[»]
ProteinModelPortaliQ9XZT6.
SMRiQ9XZT6. Positions 12-210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi67276. 8 interactions.
DIPiDIP-23491N.
IntActiQ9XZT6. 1 interaction.
MINTiMINT-879155.
STRINGi7227.FBpp0302815.

Chemistry

BindingDBiQ9XZT6.
ChEMBLiCHEMBL4760.

PTM databases

iPTMnetiQ9XZT6.

Proteomic databases

PaxDbiQ9XZT6.
PRIDEiQ9XZT6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0083707; FBpp0083121; FBgn0022338.
FBtr0321263; FBpp0302815; FBgn0022338.
GeneIDi42273.
KEGGidme:Dmel_CG5452.

Organism-specific databases

CTDi42273.
FlyBaseiFBgn0022338. dnk.

Phylogenomic databases

eggNOGiKOG4235. Eukaryota.
COG1428. LUCA.
GeneTreeiENSGT00510000046588.
InParanoidiQ9XZT6.
KOiK05961.
OMAiMYRDACR.
OrthoDBiEOG7R56T9.
PhylomeDBiQ9XZT6.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-17889.
BRENDAi2.7.1.145. 1994.
ReactomeiR-DME-73614. Pyrimidine salvage reactions.
R-DME-74217. Purine salvage.
SABIO-RKQ9XZT6.

Miscellaneous databases

EvolutionaryTraceiQ9XZT6.
GenomeRNAii42273.
NextBioi828000.
PROiQ9XZT6.

Gene expression databases

BgeeiQ9XZT6.
ExpressionAtlasiQ9XZT6. differential.
GenevisibleiQ9XZT6. DM.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR002624. DCK/DGK.
IPR031314. DNK_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF01712. dNK. 1 hit.
[Graphical view]
PIRSFiPIRSF000705. DNK. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of the multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster."
    Johansson M., Van Rompay A.R., Degreve B., Balzarini J., Karlsson A.
    J. Biol. Chem. 274:23814-23819(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION.
  2. "Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants."
    Munch-Petersen B., Knecht W., Lenz C., Sondergaard L., Piskur J.
    J. Biol. Chem. 275:6673-6679(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION.
    Strain: Oregon-R.
  3. "The genome sequence of Drosophila melanogaster."
    Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D.
    , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
    Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Berkeley.
  4. Cited for: GENOME REANNOTATION.
    Strain: Berkeley.
  5. "Four deoxynucleoside kinase activities from Drosophila melanogaster are contained within a single monomeric enzyme, a new multifunctional deoxynucleoside kinase."
    Munch-Petersen B., Piskur J., Sondergaard L.
    J. Biol. Chem. 273:3926-3931(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME ACTIVITY, SUBUNIT.
  6. "An integrated chemical, mass spectrometric and computational strategy for (quantitative) phosphoproteomics: application to Drosophila melanogaster Kc167 cells."
    Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A., Eng J.K., Aebersold R., Tao W.A.
    Mol. Biosyst. 3:275-286(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, IDENTIFICATION BY MASS SPECTROMETRY.
  7. "Phosphoproteome analysis of Drosophila melanogaster embryos."
    Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.
    J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236 AND SER-243, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Embryo.
  8. "Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase."
    Mikkelsen N.E., Johansson K., Karlsson A., Knecht W., Andersen G., Piskur J., Munch-Petersen B., Eklund H.
    Biochemistry 42:5706-5712(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-230 IN COMPLEXES WITH DEOXYTHIMIDINE AND DEOXY-TTP.
  9. "Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D."
    Welin M., Skovgaard T., Knecht W., Zhu C., Berenstein D., Munch-Petersen B., Piskur J., Eklund H.
    FEBS J. 272:3733-3742(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-230 OF MUTANT ASP-45/ASP-64 IN COMPLEXES WITH THYMIDINE AND TTP, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASN-45 AND ASN-64, ENZYME REGULATION.
  10. "Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase."
    Mikkelsen N.E., Munch-Petersen B., Eklund H.
    FEBS J. 275:2151-2160(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH DEOXY-CTP; DEOXY-GTP; DEOXY-TTP; FLOXURIDINE; AZIDO-DIDEOXYTHYMIDINE; DIDEOXYCYTIDINE AND BRIVUDINE.

Entry informationi

Entry nameiDNK_DROME
AccessioniPrimary (citable) accession number: Q9XZT6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: November 1, 1999
Last modified: May 11, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.