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

Gene ID: 1763, updated on 10-Dec-2019

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
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
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

Genomic context

See DNA2 in Genome Data Viewer
Location:
10q21.3
Exon count:
22
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 10 NC_000010.11 (68414064..68472521, complement)
105 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 phenazine biosynthesis like protein domain containing Neighboring gene Sharpr-MPRA regulatory region 82 Neighboring gene heterogeneous nuclear ribonucleoprotein H3 Neighboring gene RUN and FYVE domain containing 2 Neighboring gene ribosomal protein L26 pseudogene 29 Neighboring gene RNA, 5S ribosomal pseudogene 319 Neighboring gene solute carrier family 25 member 16 Neighboring gene ribosomal protein L26 pseudogene 27 Neighboring gene Sharpr-MPRA regulatory region 5966

Genomic regions, transcripts, and products

Expression

  • Project title: 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pathways from BioSystems

  • Cell Cycle, organism-specific biosystem (from REACTOME)
    Cell Cycle, organism-specific biosystem
    Cell Cycle
  • Cell Cycle Checkpoints, organism-specific biosystem (from REACTOME)
    Cell Cycle Checkpoints, organism-specific biosystemA hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell...
  • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
    Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
  • Chromosome Maintenance, organism-specific biosystem (from REACTOME)
    Chromosome Maintenance, organism-specific biosystemChromosome maintenance is critical for stable chromosome function in mammalian and other eukaryotic cells. Aspects of telomere maintenance and nucleosome assembly are covered here.
  • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
    DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • DNA Replication, organism-specific biosystem (from REACTOME)
    DNA Replication, organism-specific biosystemStudies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyce...
  • DNA replication, organism-specific biosystem (from KEGG)
    DNA replication, organism-specific biosystemA complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (D...
  • DNA replication, conserved biosystem (from KEGG)
    DNA replication, conserved biosystemA complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (D...
  • DNA strand elongation, organism-specific biosystem (from REACTOME)
    DNA strand elongation, organism-specific biosystemAccurate and efficient genome duplication requires coordinated processes to replicate two template strands at eucaryotic replication forks. Knowledge of the fundamental reactions involved in replicat...
  • Extension of Telomeres, organism-specific biosystem (from REACTOME)
    Extension of Telomeres, organism-specific biosystemTelomerase acts as reverse transcriptase in the elongation of telomeres (Smogorzewska and de Lange 2004).
  • G2/M Checkpoints, organism-specific biosystem (from REACTOME)
    G2/M Checkpoints, organism-specific biosystemG2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they f...
  • G2/M DNA damage checkpoint, organism-specific biosystem (from REACTOME)
    G2/M DNA damage checkpoint, organism-specific biosystemThroughout the cell cycle, the genome is constantly monitored for damage, resulting either from errors of replication, by-products of metabolism or through extrinsic sources such as ultra-violet or i...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
    HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) of replication-independent DNA double strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM fol...
  • HDR through Homologous Recombination (HRR), organism-specific biosystem (from REACTOME)
    HDR through Homologous Recombination (HRR), organism-specific biosystemHomology directed repair (HDR) through homologous recombination is known as homologous recombination repair (HRR). HRR occurs after extensive resection of DNA double strand break (DSB) ends, which cr...
  • HDR through Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
    HDR through Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) through single strand annealing (SSA), similar to HDR through homologous recombination repair (HRR), involves extensive resection of DNA double strand break ends (DSBs)...
  • Homologous DNA Pairing and Strand Exchange, organism-specific biosystem (from REACTOME)
    Homologous DNA Pairing and Strand Exchange, organism-specific biosystemThe presynaptic phase of homologous DNA pairing and strand exchange begins with the displacement of RPA from 3'-ssDNA overhangs created by extensive resection of DNA double strand break (DSB) ends. R...
  • Homology Directed Repair, organism-specific biosystem (from REACTOME)
    Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
  • Lagging Strand Synthesis, organism-specific biosystem (from REACTOME)
    Lagging Strand Synthesis, organism-specific biosystemDue to the antiparallel nature of DNA, DNA polymerization is unidirectional, and one strand is synthesized discontinuously. This strand is called the lagging strand. Although the polymerase switching...
  • Presynaptic phase of homologous DNA pairing and strand exchange, organism-specific biosystem (from REACTOME)
    Presynaptic phase of homologous DNA pairing and strand exchange, organism-specific biosystemThe presynaptic phase of homologous DNA pairing and strand exchange during homologous recombination repair (HRR) begins with the displacement of RPA from ssDNA (Thompson and Limoli 2003) by the joint...
  • Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
    Processing of DNA double-strand break ends, organism-specific biosystemHomology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ci...
  • Processive synthesis on the C-strand of the telomere, organism-specific biosystem (from REACTOME)
    Processive synthesis on the C-strand of the telomere, organism-specific biosystemOnce polymerase switching from pol alpha to pol delta is complete the processive synthesis of a short run of DNA called an Okazaki fragment begins. DNA synthesis is discontinuous and as the extending...
  • Processive synthesis on the lagging strand, organism-specific biosystem (from REACTOME)
    Processive synthesis on the lagging strand, organism-specific biosystemThe key event that allows the processive synthesis on the lagging strand, is polymerase switching from pol alpha to pol delta, as on the leading strand. However, the processive synthesis on the laggi...
  • Regulation of TP53 Activity, organism-specific biosystem (from REACTOME)
    Regulation of TP53 Activity, organism-specific biosystemProtein stability and transcriptional activity of TP53 (p53) tumor suppressor are regulated by post-translational modifications that include ubiquitination, phosphorylation, acetylation, methylation,...
  • Regulation of TP53 Activity through Phosphorylation, organism-specific biosystem (from REACTOME)
    Regulation of TP53 Activity through Phosphorylation, organism-specific biosystemPhosphorylation of TP53 (p53) at the N-terminal serine residues S15 and S20 plays a critical role in protein stabilization as phosphorylation at these sites interferes with binding of the ubiquitin l...
  • Removal of the Flap Intermediate, organism-specific biosystem (from REACTOME)
    Removal of the Flap Intermediate, organism-specific biosystemTwo endonucleases, Dna2 and flap endonuclease 1 (FEN-1), are responsible for resolving the nascent flap structure (Tsurimoto and Stillman 1991). The Dna2 endonuclease/helicase in yeast is a monomer o...
  • Removal of the Flap Intermediate from the C-strand, organism-specific biosystem (from REACTOME)
    Removal of the Flap Intermediate from the C-strand, organism-specific biosystemTwo endonucleases, Dna2 and flap endonuclease 1 (FEN-1), are responsible for resolving the nascent flap structure (Tsurimoto and Stillman 1991). The Dna2 endonuclease/helicase in yeast is a monomer o...
  • Resolution of D-Loop Structures, organism-specific biosystem (from REACTOME)
    Resolution of D-Loop Structures, organism-specific biosystemOnce repair synthesis has occurred, the D-loop structure may be resolved either through Holliday junction intermediates or through synthesis-dependent strand-annealing (SDSA) (Prado and Aguilera 2003...
  • Resolution of D-loop Structures through Holliday Junction Intermediates, organism-specific biosystem (from REACTOME)
    Resolution of D-loop Structures through Holliday Junction Intermediates, organism-specific biosystemD-loops generated after strand invasion and DNA repair synthesis during homologous recombination repair (HRR) can be resolved through Holliday junction intermediates.A D-loop can be cleaved by the co...
  • Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA), organism-specific biosystem (from REACTOME)
    Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA), organism-specific biosystemIn the synthesis-dependent strand-annealing (SDSA) model of D-loop resolution, D-loop strands extended by DNA repair synthesis dissociate from their sister chromatid complements and reanneal with the...
  • S Phase, organism-specific biosystem (from REACTOME)
    S Phase, organism-specific biosystemDNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues,...
  • Synthesis of DNA, organism-specific biosystem (from REACTOME)
    Synthesis of DNA, organism-specific biosystemThe actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of ...
  • Telomere C-strand (Lagging Strand) Synthesis, organism-specific biosystem (from REACTOME)
    Telomere C-strand (Lagging Strand) Synthesis, organism-specific biosystemDue to the antiparallel nature of DNA, DNA polymerization is unidirectional, and one strand is synthesized discontinuously. This strand is called the lagging strand. Although the polymerase switching...
  • Telomere Maintenance, organism-specific biosystem (from REACTOME)
    Telomere Maintenance, organism-specific biosystemTelomeres are protein-DNA complexes at the ends of linear chromosomes that are important for genome stability. Telomeric DNA in humans, as in many eukaryotic organisms, consists of tandem repeats (B...
  • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
    Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ10063, KIAA0083, MGC133297

Gene Ontology Provided by GOA

Function Evidence Code Pubs
4 iron, 4 sulfur cluster binding IEA
Inferred from Electronic Annotation
more info
 
5'-3' DNA helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
5'-flap endonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
5'-flap endonuclease activity IDA
Inferred from Direct Assay
more info
PubMed 
ATP binding IEA
Inferred from Electronic Annotation
more info
 
ATPase activity TAS
Traceable Author Statement
more info
PubMed 
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
DNA helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
NOT DNA helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
RNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
helicase activity TAS
Traceable Author Statement
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
nuclease activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
single-stranded DNA-dependent ATP-dependent DNA helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
site-specific endodeoxyribonuclease activity, specific for altered base IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
DNA double-strand break processing IDA
Inferred from Direct Assay
more info
PubMed 
DNA duplex unwinding IEA
Inferred from Electronic Annotation
more info
 
DNA replication IMP
Inferred from Mutant Phenotype
more info
PubMed 
DNA replication TAS
Traceable Author Statement
more info
 
DNA replication checkpoint IMP
Inferred from Mutant Phenotype
more info
PubMed 
DNA replication, Okazaki fragment processing IDA
Inferred from Direct Assay
more info
PubMed 
DNA replication, removal of RNA primer IDA
Inferred from Direct Assay
more info
PubMed 
G-quadruplex DNA unwinding TAS
Traceable Author Statement
more info
PubMed 
base-excision repair IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrial DNA repair IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrial DNA replication IDA
Inferred from Direct Assay
more info
PubMed 
mitotic telomere maintenance via semi-conservative replication ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
nucleic acid phosphodiester bond hydrolysis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of DNA replication IDA
Inferred from Direct Assay
more info
PubMed 
regulation of signal transduction by p53 class mediator TAS
Traceable Author Statement
more info
 
replication fork reversal IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
t-circle formation TAS
Traceable Author Statement
more info
PubMed 
telomere maintenance ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
telomere maintenance via semi-conservative replication TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
colocalizes_with gamma DNA polymerase complex IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrial nucleoid IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrion IDA
Inferred from Direct Assay
more info
 
nuclear chromosome, telomeric region IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nuclear chromosome, telomeric region ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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

NCBI Reference Sequences (RefSeq)

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_001080449.3NP_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
    Related
    ENSP00000351185.3, ENST00000358410.8
    Conserved Domains (5) summary
    TIGR00376
    Location:4711032
    TIGR00376; DNA helicase, putative
    pfam08696
    Location:71282
    Dna2; DNA replication factor Dna2
    pfam13087
    Location:8051017
    AAA_12; AAA domain
    cl00641
    Location:261397
    Cas4_I-A_I-B_I-C_I-D_II-B; CRISPR/Cas system-associated protein Cas4
    cl21455
    Location:625875
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

RNA

  1. NR_102264.1 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: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p13 Primary Assembly

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

mRNA and Protein(s)

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

    Conserved Domains (5) summary
    TIGR00376
    Location:5011062
    TIGR00376; DNA helicase, putative
    pfam08696
    Location:101312
    Dna2; DNA replication factor Dna2
    pfam13087
    Location:8351047
    AAA_12; AAA domain
    cl00641
    Location:291427
    Cas4_I-A_I-B_I-C_I-D_II-B; CRISPR/Cas system-associated protein Cas4
    cl21455
    Location:655905
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
  2. XM_017015799.1XP_016871288.1  DNA replication ATP-dependent helicase/nuclease DNA2 isoform X2

  3. XM_011539417.1XP_011537719.1  DNA replication ATP-dependent helicase/nuclease DNA2 isoform X3

    Conserved Domains (3) summary
    TIGR00376
    Location:111672
    TIGR00376; DNA helicase, putative
    pfam13087
    Location:445657
    AAA_12; AAA domain
    cl21455
    Location:265515
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
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