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

Gene ID: 1763, updated on 3-Nov-2024

Summary

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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
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Genomic context

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See DNA2 in Genome Data Viewer
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_000010.11Genomic Context describing neighboring genes Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16457 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16478 Neighboring gene MPRA-validated peak989 silencer Neighboring gene MPRA-validated peak990 silencer Neighboring gene phenazine biosynthesis like protein domain containing Neighboring gene MPRA-validated peak991 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3460 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3461 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3462 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:70091533-70092347 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:70092348-70093161 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16564 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16571 Neighboring gene heterogeneous nuclear ribonucleoprotein H3 Neighboring gene MPRA-validated peak992 silencer Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16583 Neighboring gene RUN and FYVE domain containing 2 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16593 Neighboring gene MPRA-validated peak994 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:70166191-70166692 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:70166693-70167192 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16635 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16643 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16656 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_16661/16662 and experimental_16666/16667 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16674 Neighboring gene ribosomal protein L26 pseudogene 29 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16683 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16686/16687 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16694 Neighboring gene RNA, 5S ribosomal pseudogene 319 Neighboring gene MPRA-validated peak997 silencer Neighboring gene solute carrier family 25 member 16 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:70255753-70256326 Neighboring gene ribosomal protein L26 pseudogene 27 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:70285872-70286556 Neighboring gene Sharpr-MPRA regulatory region 5966 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:70287929-70288614 Neighboring gene transmembrane protein 14D, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Isolation of human Dna2 endonuclease and characterization of its enzymatic properties. Kim JH, et al. Nucleic Acids Res, 2006. PMID 16595799, Free PMC Article
  2. The iron-sulphur cluster in human DNA2 is required for all biochemical activities of DNA2. Mariotti L, et al. Commun Biol, 2020 Jun 23. PMID 32576938, Free PMC Article
  3. Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue. Appanah R, et al. Curr Genet, 2020 Dec. PMID 32909097, Free PMC Article
  4. Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases. Zheng L, et al. Nucleic Acids Res, 2020 Jan 10. PMID 31754720, Free PMC Article
  5. Dna2 on the road to Okazaki fragment processing and genome stability in eukaryotes. Kang YH, et al. Crit Rev Biochem Mol Biol, 2010 Apr. PMID 20131965

See all (81) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma.
    Title: Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma.
  4. 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.
  5. 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.
  6. The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.
    Title: The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.
  7. 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.
  8. 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.
  9. 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.
  10. 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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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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Markers

Homology

Clone Names

  • FLJ10063, KIAA0083, MGC133297

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 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
XP_006717743.1
XP_011537719.1
XP_016871288.1
XP_054220919.1
XP_054220920.1
XP_054220921.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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

  1. NG_034247.1 RefSeqGene

    Range
    5001..62910
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  1. 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

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    68414064..68472521 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. XM_017015799.1 → XP_016871288.1  DNA replication ATP-dependent helicase/nuclease DNA2 isoform X2

  3. 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

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    69283292..69341758 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054364944.1 → XP_054220919.1  DNA replication ATP-dependent helicase/nuclease DNA2 isoform X1

  2. XM_054364945.1 → XP_054220920.1  DNA replication ATP-dependent helicase/nuclease DNA2 isoform X2

  3. XM_054364946.1 → XP_054220921.1  DNA replication ATP-dependent helicase/nuclease DNA2 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51530.3 GenPept UniProtKB/Swiss-Prot:P51530

Gene LinkOut

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