Protein: DNA replication ATP-dependent helicase/nuclease DNA2 (hDNA2) (DNA replication ATP-dependent helicase-like homolog) [Includes: DNA replication nuclease DNA2 (EC 3.1.-.-); DNA replication ATP-dependent helicase DNA2 (EC 3.6.4.12)] (P51530)
Organism: Homo sapiens (Human)
Function: 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 weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function.
Subcellular location: Nucleus. Mitochondrion. Note=Was initially reported to be exclusively mitochondrial (PubMed:18995831). However, it was later shown to localize both in mitochondrion and nucleus (PubMed:19487465). {ECO:0000269|PubMed:18995831, ECO:0000269|PubMed:19487465}.
Sequence: MEQLNELELLMEKSFWEEAELPAELFQKKVVASFPRTVLSTGMDNRYLVLAVNTVQNKEGNCEKRLVITASQSLENKELCILRNDWCSVPVEPGDIIHLEGDCTSDTWIIDKDFGYLILYPDMLISGTSIASSIRCMRRAVLSETFRSSDPATRQMLIGTVLHEVFQKAINNSFAPEKLQELAFQTIQEIRHLKEMYRLNLSQDEIKQEVEDYLPSFCKWAGDFMHKNTSTDFPQMQLSLPSDNSKDNSTCNIEVVKPMDIEESIWSPRFGLKGKIDVTVGVKIHRGYKTKYKIMPLELKTGKESNSIEHRSQVVLYTLLSQERRADPEAGLLLYLKTGQMYPVPANHLDKRELLKLRNQMAFSLFHRISKSATRQKTQLASLPQIIEEEKTCKYCSQIGNCALYSRAVEQQMDCSSVPIVMLPKIEEETQHLKQTHLEYFSLWCLMLTLESQSKDNKKNHQNIWLMPASEMEKSGSCIGNLIRMEHVKIVCDGQYLHNFQCKHGAIPVTNLMAGDRVIVSGEERSLFALSRGYVKEINMTTVTCLLDRNLSVLPESTLFRLDQEEKNCDIDTPLGNLSKLMENTFVSKKLRDLIIDFREPQFISYLSSVLPHDAKDTVACILKGLNKPQRQAMKKVLLSKDYTLIVGMPGTGKTTTICTLVRILYACGFSVLLTSYTHSAVDNILLKLAKFKIGFLRLGQIQKVHPAIQQFTEQEICRSKSIKSLALLEELYNSQLIVATTCMGINHPIFSRKIFDFCIVDEASQISQPICLGPLFFSRRFVLVGDHQQLPPLVLNREARALGMSESLFKRLEQNKSAVVQLTVQYRMNSKIMSLSNKLTYEGKLECGSDKVANAVINLRHFKDVKLELEFYADYSDNPWLMGVFEPNNPVCFLNTDKVPAPEQVEKGGVSNVTEAKLIVFLTSIFVKAGCSPSDIGIIAPYRQQLKIINDLLARSIGMVEVNTVDKYQGRDKSIVLVSFVRSNKDGTVGELLKDWRRLNVAITRAKHKLILLGCVPSLNCYPPLEKLLNHLNSEKLIIDLPSREHESLCHILGDFQRE
InterPro domains: - IPR041677: DNA2/NAM7 helicase, helicase domain (domain) [626-797]
- IPR047187: Upf1-like, C-terminal helicase domain (domain) [829-1033]
- IPR051827: CRISPR-associated exonuclease Cas4 (family) [11-551]
- IPR011604: PD-(D/E)XK endonuclease-like domain superfamily (homologous_superfamily) [125-403]
- IPR041679: DNA2/NAM7 helicase-like, C-terminal (domain) [805-1016]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [558-1044]
- IPR048459: DNA2, rift barrel domain (domain) [469-566]
- IPR026851: DNA replication ATP-dependent helicase/nuclease Dna2/JHS1, DEXXQ-box helicase domain (domain) [625-828]
- IPR014808: DNA replication factor Dna2, N-terminal (domain) [74-281]
Interaction partners: - Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
- Exonuclease 1
- DNA topoisomerase 3-alpha
- WD repeat and HMG-box DNA-binding protein 1
- Replication protein A 70 kDa DNA-binding subunit
- Flap endonuclease 1
- RecQ-mediated genome instability protein 1
- RecQ-like DNA helicase BLM
- DNA repair protein RAD51 homolog 1
- DNA endonuclease RBBP8
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140657 (ATP-dependent activity), GO:0140640 (catalytic activity, acting on a nucleic acid), GO:0004386 (helicase activity), GO:0008094 (ATP-dependent activity, acting on DNA), GO:0005515 (protein binding), GO:0140097 (catalytic activity, acting on DNA), GO:0003678 (DNA helicase activity), GO:0043139 (5'-3' DNA helicase activity), GO:0017116 (single-stranded DNA helicase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0050896 (response to stimulus), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0033554 (cellular response to stress), GO:0006259 (DNA metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0006281 (DNA repair), GO:0006302 (double-strand break repair), GO:0045002 (double-strand break repair via single-strand annealing)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0098687 (chromosomal region), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0000781 (chromosome, telomeric region), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005694 (chromosome), GO:0005634 (nucleus)