{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P51530","secondaryAccessions":["Q2NKM1","Q5TC49","Q5TC50","Q6P455","Q6PI80","Q7Z6H9","Q8N346"],"uniProtkbId":"DNA2_HUMAN","entryAudit":{"firstPublicDate":"1996-10-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2006-12-12","entryVersion":192,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"DNA replication ATP-dependent helicase/nuclease DNA2"},"shortNames":[{"value":"hDNA2"}]},"alternativeNames":[{"fullName":{"value":"DNA replication ATP-dependent helicase-like homolog"}}],"includes":[{"recommendedName":{"fullName":{"value":"DNA replication nuclease DNA2"},"ecNumbers":[{"value":"3.1.-.-"}]}},{"recommendedName":{"fullName":{"value":"DNA replication ATP-dependent helicase DNA2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16595800"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20019387"}],"value":"5.6.2.3"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"DNA 5'-3' helicase DNA2"}}]}]},"genes":[{"geneName":{"value":"DNA2"},"synonyms":[{"value":"DNA2L"},{"value":"KIAA0083"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16595799"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16595800"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18995831"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19487465"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21325134"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21572043"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22570407"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22570476"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31478350"}],"value":"Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is absent to weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Couples ATP hydrolysis with the unwinding of duplex DNA at the replication fork by translocating in the 5'-3' direction.","ecNumber":"5.6.2.3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16595800"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20019387"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"ATP + H2O = ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:13065"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"5.6.2.3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16595800"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20019387"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"[4Fe-4S] cluster","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P38859"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:49883"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P38859"}],"value":"Binds 1 [4Fe-4S] cluster."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21325134"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22570476"}],"value":"Interacts with BLM and WDHD1"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18995831"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19487465"}],"value":"Was initially reported to be exclusively mitochondrial (PubMed:18995831). However, it was later shown to localize both in mitochondrion and nucleus (PubMed:19487465)"}]},"subcellularLocations":[{"location":{"value":"Nucleus","id":"SL-0191"}},{"location":{"value":"Mitochondrion","id":"SL-0173"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P51530-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P51530-2"],"sequenceIds":["VSP_021870","VSP_021871"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P51530-3"],"sequenceIds":["VSP_021869"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["P51530-4"],"sequenceIds":["VSP_044185"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20019387"}],"value":"Acetylated by EP300, leading to stimulation of the 5'-3' endonuclease, and small increases in the weak 5'-3' helicase and DNA-dependent ATPase activities, possibly by increasing DNA substrate affinity"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6","diseaseAccession":"DI-03758","acronym":"PEOA6","description":"A disorder characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA deletions on muscle biopsy. 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