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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
    mouse all
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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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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