dnk deoxyribonucleoside kinase [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: dnkprovided by FlyBase
Official Full Name: deoxyribonucleoside kinaseprovided by FlyBase
Primary source: FLYBASE:FBgn0022338
Locus tag: Dmel_CG5452
See related: AllianceGenome:FB:FBgn0022338
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: CG5452; Dm-dNK; DM-dNK; DmdNK; Dmel\CG5452; dNK; DNK
Summary: Enables deoxynucleoside kinase activity. Involved in nucleoside diphosphate phosphorylation. Located in cytoplasm. Is expressed in several structures, including embryonic brain; extended germ band embryo; gut section; imaginal disc; and pole plasm. Human ortholog(s) of this gene implicated in autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions 3 and mitochondrial DNA depletion syndrome 2. Orthologous to human TK2 (thymidine kinase 2). [provided by Alliance of Genome Resources, Apr 2022]
Orthologs: all
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Genomic context

Location:: 91E2-91E2; 3-65 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3R	NT_033777.3 (18980995..18982749)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3R	NT_033777.2 (14806717..14808471)

Chromosome 3R - NT_033777.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

We showed that sensitivity of the osteosarcoma cell line to the nucleoside analogs and the efficiency of bystander cell killing were independent of the subcellular localization of Dm-dNK.
Title: Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria.
Report synergistic antitumor effect of adenovirus armed with Drosophila melanogaster deoxyribonucleoside kinase and nucleoside analogs for human breast carcinoma.
Title: Synergistic antitumor effect of adenovirus armed with Drosophila melanogaster deoxyribonucleoside kinase and nucleoside analogs for human breast carcinoma in vitro and in vivo.
Data indicate that long term Dm-dNK ( nucleoside kinase from Drosophila melanogaster) expression rescued thymidine kinase 2 (Tk2)-deficient mice without lethal side effects.
Title: Long term expression of Drosophila melanogaster nucleoside kinase in thymidine kinase 2-deficient mice with no lethal effects caused by nucleotide pool imbalances.
Transgene expression of Drosophila melanogaster nucleoside kinase reverses mitochondrial thymidine kinase 2 deficiency
Title: Transgene expression of Drosophila melanogaster nucleoside kinase reverses mitochondrial thymidine kinase 2 deficiency.
Multisubstrate deoxyribonucleoside kinase could be used in a novel therapeutic strategy for treating breast cancer and improving anti-tumor efficacy, as well as for optimizing approaches for suicide gene therapy.
Title: The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster as a therapeutic suicide gene of breast cancer cells.
Structural studies of nucleoside analog and feedback inhibition binding to Drosophila melanogaster multisubstrate dnk are reported.
Title: Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase.
observations give insight into the mechanisms of substrate binding and catalysis, which is important for developing novel suicide genes and drugs for use in gene therapy
Title: Functional studies of active-site mutants from Drosophila melanogaster deoxyribonucleoside kinase. Investigations of the putative catalytic glutamate-arginine pair and of residues responsible for substrate specificity.
Results describe active-site mutants of Drosophila deoxyribonucleoside kinase (Dm-DNK) with reduced phosphorylation efficiency, supporting their importance for substrate binding and/or catalysis as proposed by the recently solved structure of Dm-dNK.
Title: Active site mutants of Drosophila melanogaster multisubstrate deoxyribonucleoside kinase.
This strongly suggests that dNK plays a role in cell proliferation in physiological conditions.
Title: In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance.
mechanism of feedback inhibition is presented based on the crystal structure of a complex between deoxyribonucleoside kinase and its feedback inhibitor deoxythymidine triphosphate
Title: Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables cytidine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxyadenosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxycytidine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxyguanosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxynucleoside kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables deoxynucleoside kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxynucleoside kinase activity	IEA Inferred from Electronic Annotation more info
enables kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables thymidine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables uridine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in nucleobase-containing compound metabolic process	IEA Inferred from Electronic Annotation more info
involved_in nucleoside phosphate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleoside salvage	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: deoxyribonucleoside kinase

Names: 2'-deoxynucleoside kinase; CG5452-PA; CG5452-PB; deoxynucleoside kinase; deoxyribonucleoside; dnk-PA; dnk-PB; kinase

NP_001262722.1

EC 2.7.1.113

EC 2.7.1.145

EC 2.7.1.21

EC 2.7.1.213

EC 2.7.1.74

EC 2.7.1.76

NP_524399.1

EC 2.7.1.113

EC 2.7.1.145

EC 2.7.1.21

EC 2.7.1.213

EC 2.7.1.74

EC 2.7.1.76

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033777.3 Reference assembly

Range

18980995..18982749

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001275793.1 → NP_001262722.1 deoxyribonucleoside kinase, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001262722.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9XZT6

UniProtKB/TrEMBL

Q540Z9

Conserved Domains (1) summary

cd01673
Location:23 → 214

dNK; Deoxyribonucleoside kinase (dNK) catalyzes the phosphorylation of deoxyribonucleosides to yield corresponding monophosphates (dNMPs). This family consists of various deoxynucleoside kinases including deoxyribo- cytidine (EC 2.7.1.74), guanosine (EC 2.7.1. ...
NM_079675.3 → NP_524399.1 deoxyribonucleoside kinase, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_524399.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9XZT6

UniProtKB/TrEMBL

Q540Z9

Related

FBpp0083121

Conserved Domains (1) summary

cd01673
Location:23 → 214

dNK; Deoxyribonucleoside kinase (dNK) catalyzes the phosphorylation of deoxyribonucleosides to yield corresponding monophosphates (dNMPs). This family consists of various deoxynucleoside kinases including deoxyribo- cytidine (EC 2.7.1.74), guanosine (EC 2.7.1. ...