DNA2 DNA replication helicase/nuclease 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DNA2provided by HGNC
Official Full Name: DNA replication helicase/nuclease 2provided by HGNC
Primary source: HGNC:HGNC:2939
See related: Ensembl:ENSG00000138346 MIM:601810; AllianceGenome:HGNC:2939
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RTS4; DNA2L; hDNA2
Summary: This gene encodes a member of the DNA2/NAM7 helicase family. The encoded protein is a conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. Mutations in this gene are associated with autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) and Seckel syndrome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
Expression: Broad expression in lymph node (RPKM 2.7), testis (RPKM 1.9) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q21.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (68414064..68472521, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (69283292..69341758, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (70173821..70231878, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.
Title: USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.
EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.
Title: EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.
Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma.
Title: Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma.
FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.
Title: FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.
Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma.
Title: Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma.
The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.
Title: The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.
Up-regulation of DNA2 results in cell proliferation and migration in endometriosis.
Title: Up-regulation of DNA2 results in cell proliferation and migration in endometriosis.
Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.
Title: Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.
The iron-sulphur cluster in human DNA2 is required for all biochemical activities of DNA2.
Title: The iron-sulphur cluster in human DNA2 is required for all biochemical activities of DNA2.
Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue.
Title: Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mitochondrial DNA deletion syndrome with progressive myopathy MedGen: C3554599 OMIM: 615156 GeneReviews: Mitochondrial DNA Maintenance Defects Overview	not available
Seckel syndrome 8 MedGen: C3891452 OMIM: 615807 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S274 (e-PCR)
- UniSTS:147991

D10S309 (e-PCR)
- UniSTS:148030

RH25311 (e-PCR)
- UniSTS:36266

D10S2165 (e-PCR)
- UniSTS:40119

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables 5'-3' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables 5'-flap endonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables 5'-flap endonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables 5'-flap endonuclease activity	TAS Traceable Author Statement more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP hydrolysis activity	TAS Traceable Author Statement more info	PubMed
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
NOT enables DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables RNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables helicase activity	TAS Traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables nuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables site-specific endodeoxyribonuclease activity, specific for altered base	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA double-strand break processing	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
involved_in DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication, Okazaki fragment processing	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA replication, removal of RNA primer	IDA Inferred from Direct Assay more info	PubMed
involved_in G-quadruplex DNA unwinding	TAS Traceable Author Statement more info	PubMed
involved_in base-excision repair	IDA Inferred from Direct Assay more info	PubMed
involved_in base-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in mitotic telomere maintenance via semi-conservative replication	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in nucleic acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in replication fork reversal	IBA Inferred from Biological aspect of Ancestor more info
involved_in t-circle formation	TAS Traceable Author Statement more info	PubMed
involved_in telomere maintenance	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in telomere maintenance via semi-conservative replication	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in chromosome, telomeric region	ISS Inferred from Sequence or Structural Similarity more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
part_of gamma DNA polymerase complex	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial nucleoid	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA replication ATP-dependent helicase/nuclease DNA2

Names: DNA replication ATP-dependent helicase-like homolog; DNA replication helicase 2 homolog; DNA2 DNA replication helicase 2-like; DNA2-like helicase

NP_001073918.2

EC 3.6.4.12

XP_006717743.1

EC 3.6.4.12

XP_011537719.1

EC 3.6.4.12

XP_016871288.1

EC 3.6.4.12

XP_054220919.1

EC 3.6.4.12

XP_054220920.1

EC 3.6.4.12

XP_054220921.1

EC 3.6.4.12

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_034247.1 RefSeqGene

Range

5001..62910

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001080449.3 → NP_001073918.2 DNA replication ATP-dependent helicase/nuclease DNA2

See identical proteins and their annotated locations for NP_001073918.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the functional protein.

Source sequence(s)

BC073945, D42046, DC404138

Consensus CDS

CCDS44415.2

UniProtKB/Swiss-Prot

P51530, Q2NKM1, Q5TC49, Q5TC50, Q6P455, Q6PI80, Q7Z6H9, Q8N346

Related

ENSP00000351185.3, ENST00000358410.8

Conserved Domains (5) summary

TIGR00376
Location:471 → 1032

TIGR00376; DNA helicase, putative

pfam08696
Location:71 → 282

Dna2; DNA replication factor Dna2

pfam13087
Location:805 → 1017

AAA_12; AAA domain

cl00641
Location:261 → 397

Cas4_I-A_I-B_I-C_I-D_II-B; CRISPR/Cas system-associated protein Cas4

cl21455
Location:625 → 875

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

RNA

NR_102264.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs at the 5' end and uses an alternate internal splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC063664, BC111740

Related

ENST00000551118.6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

68414064..68472521 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006717680.3 → XP_006717743.1 DNA replication ATP-dependent helicase/nuclease DNA2 isoform X1

Conserved Domains (5) summary

TIGR00376
Location:501 → 1062

TIGR00376; DNA helicase, putative

pfam08696
Location:101 → 312

Dna2; DNA replication factor Dna2

pfam13087
Location:835 → 1047

AAA_12; AAA domain

cl00641
Location:291 → 427

Cas4_I-A_I-B_I-C_I-D_II-B; CRISPR/Cas system-associated protein Cas4

cl21455
Location:655 → 905

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
XM_017015799.1 → XP_016871288.1 DNA replication ATP-dependent helicase/nuclease DNA2 isoform X2
XM_011539417.1 → XP_011537719.1 DNA replication ATP-dependent helicase/nuclease DNA2 isoform X3

Conserved Domains (3) summary

TIGR00376
Location:111 → 672

TIGR00376; DNA helicase, putative

pfam13087
Location:445 → 657

AAA_12; AAA domain

cl21455
Location:265 → 515

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

69283292..69341758 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054364944.1 → XP_054220919.1 DNA replication ATP-dependent helicase/nuclease DNA2 isoform X1
XM_054364945.1 → XP_054220920.1 DNA replication ATP-dependent helicase/nuclease DNA2 isoform X2
XM_054364946.1 → XP_054220921.1 DNA replication ATP-dependent helicase/nuclease DNA2 isoform X3