DNA2

Protein identityUniProt · HPA

UniProt accession

P51530

Gene

DNA2

Ensembl

ENSG00000138346

Chromosome

10

Canonical length

1060 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1060 residues, UniProt reviewed canonical sequence.

>P51530|DNA2
     1  MEQLNELELL MEKSFWEEAE LPAELFQKKV VASFPRTVLS TGMDNRYLVL AVNTVQNKEG
    61  NCEKRLVITA SQSLENKELC ILRNDWCSVP VEPGDIIHLE GDCTSDTWII DKDFGYLILY
   121  PDMLISGTSI ASSIRCMRRA VLSETFRSSD PATRQMLIGT VLHEVFQKAI NNSFAPEKLQ
   181  ELAFQTIQEI RHLKEMYRLN LSQDEIKQEV EDYLPSFCKW AGDFMHKNTS TDFPQMQLSL
   241  PSDNSKDNST CNIEVVKPMD IEESIWSPRF GLKGKIDVTV GVKIHRGYKT KYKIMPLELK
   301  TGKESNSIEH RSQVVLYTLL SQERRADPEA GLLLYLKTGQ MYPVPANHLD KRELLKLRNQ
   361  MAFSLFHRIS KSATRQKTQL ASLPQIIEEE KTCKYCSQIG NCALYSRAVE QQMDCSSVPI
   421  VMLPKIEEET QHLKQTHLEY FSLWCLMLTL ESQSKDNKKN HQNIWLMPAS EMEKSGSCIG
   481  NLIRMEHVKI VCDGQYLHNF QCKHGAIPVT NLMAGDRVIV SGEERSLFAL SRGYVKEINM
   541  TTVTCLLDRN LSVLPESTLF RLDQEEKNCD IDTPLGNLSK LMENTFVSKK LRDLIIDFRE
   601  PQFISYLSSV LPHDAKDTVA CILKGLNKPQ RQAMKKVLLS KDYTLIVGMP GTGKTTTICT
   661  LVRILYACGF SVLLTSYTHS AVDNILLKLA KFKIGFLRLG QIQKVHPAIQ QFTEQEICRS
   721  KSIKSLALLE ELYNSQLIVA TTCMGINHPI FSRKIFDFCI VDEASQISQP ICLGPLFFSR
   781  RFVLVGDHQQ LPPLVLNREA RALGMSESLF KRLEQNKSAV VQLTVQYRMN SKIMSLSNKL
   841  TYEGKLECGS DKVANAVINL RHFKDVKLEL EFYADYSDNP WLMGVFEPNN PVCFLNTDKV
   901  PAPEQVEKGG VSNVTEAKLI VFLTSIFVKA GCSPSDIGII APYRQQLKII NDLLARSIGM
   961  VEVNTVDKYQ GRDKSIVLVS FVRSNKDGTV GELLKDWRRL NVAITRAKHK LILLGCVPSL
  1021  NCYPPLEKLL NHLNSEKLII DLPSREHESL CHILGDFQRE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DNA2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

7.6 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DNA2.

Disease | AllUniProt

Conditions DNA2 is implicated in, by any mechanism.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6 (PEOA6) MIM:615156
• Seckel syndrome 8 (SCKL8) MIM:615807
• Rothmund-Thomson syndrome 4 (RTS4) MIM:620819

Disease | GeneticClinVar

18 pathogenic / likely-pathogenic of 1,024 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Rothmund-Thomson syndrome
• Rothmund-Thomson syndrome type 4
• Mitochondrial DNA deletion syndrome with progressive myopathy
• Seckel syndrome 8
• Ateleiotic dwarfism

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.93

gnomAD pLI

0

gnomAD missense Z

0.74

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• base-excision repair
• DNA double-strand break processing
• DNA geometric change
• DNA replication
• DNA replication checkpoint signaling
• DNA replication, removal of RNA primer
• mitochondrial DNA repair
• mitochondrial DNA replication
• mitotic telomere maintenance via semi-conservative replication
• positive regulation of DNA replication
• replication fork reversal
• t-circle formation
• telomere maintenance
• telomere maintenance via semi-conservative replication
• DNA replication, Okazaki fragment processing

Molecular functions

• 4 iron, 4 sulfur cluster binding
• 5'-3' DNA helicase activity
• 5'-flap endonuclease activity
• ATP binding
• ATP hydrolysis activity
• deoxyribonuclease (pyrimidine dimer) activity
• DNA binding
• DNA helicase activity
• helicase activity
• metal ion binding
• nuclease activity
• RNA binding
• single-stranded DNA helicase activity

Cellular components

• chromosome, telomeric region
• cytoplasm
• mitochondrial nucleoid
• mitochondrion
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• PD-(D/E)XK endonuclease-like domain superfamily
• P-loop containing nucleoside triphosphate hydrolase
• DNA2/NAM7 helicase, helicase domain
• DNA2/NAM7 helicase-like, C-terminal
• Upf1-like, C-terminal helicase domain
• AAA domain
• AAA domain
• DNA replication factor Dna2, N-terminal
• DNA replication ATP-dependent helicase/nuclease Dna2/JHS1, DEXXQ-box helicase domain
• DNA2, rift barrel domain
• CRISPR-associated exonuclease Cas4
• DNA replication factor Dna2
• Dna2 Rift barrel domain

KeywordsUniProt

• 4Fe-4S
• Acetylation
• ATP-binding
• DNA damage
• DNA repair
• DNA replication
• DNA-binding
• Dwarfism
• Ectodermal dysplasia
• Endonuclease
• Helicase
• Hydrolase
• Hypotrichosis
• Intellectual disability
• Iron
• Iron-sulfur
• Metal-binding
• Mitochondrion
• Multifunctional enzyme
• Nuclease
• Nucleotide-binding
• Nucleus
• Primary mitochondrial disease
• Progressive external ophthalmoplegia

InteractionsUniProt · HPA

Protein binding partners of DNA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BLM
• WDHD1
• CIAO1
• CIAO2B
• MMS19
• PTGES3