ID Q8IRL9_DROME Unreviewed; 1100 AA. AC Q8IRL9; DT 01-MAR-2003, integrated into UniProtKB/TrEMBL. DT 01-MAR-2003, sequence version 1. DT 10-FEB-2021, entry version 146. DE RecName: Full=DNA replication ATP-dependent helicase/nuclease {ECO:0000256|RuleBase:RU367041}; DE EC=3.1.-.- {ECO:0000256|RuleBase:RU367041}; DE EC=3.6.4.12 {ECO:0000256|RuleBase:RU367041}; GN Name=DNA2 {ECO:0000313|EMBL:AAN09623.1}; GN Synonyms=CG2990-RB {ECO:0000313|EMBL:ACS78060.1}, Dmel\CG2990 GN {ECO:0000313|EMBL:AAN09623.1}; GN ORFNames=CG2990 {ECO:0000313|EMBL:AAN09623.1, GN ECO:0000313|FlyBase:FBgn0030170}, Dmel_CG2990 GN {ECO:0000313|EMBL:AAN09623.1}; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227 {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803}; RN [1] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.H., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Gabor G.L., Abril J.F., Agbayani A., RA An H.J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., Spier E., RA Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., RA Turner R., Venter E., Wang A.H., Wang X., Wang Z.Y., Wassarman D.A., RA Weinstock G.M., Weissenbach J., Williams S.M., WoodageT, Worley K.C., RA Wu D., Yang S., Yao Q.A., Ye J., Yeh R.F., Zaveri J.S., Zhan M., Zhang G., RA Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S., RA Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [2] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537568; RA Celniker S.E., Wheeler D.A., Kronmiller B., Carlson J.W., Halpern A., RA Patel S., Adams M., Champe M., Dugan S.P., Frise E., Hodgson A., RA George R.A., Hoskins R.A., Laverty T., Muzny D.M., Nelson C.R., RA Pacleb J.M., Park S., Pfeiffer B.D., Richards S., Sodergren E.J., RA Svirskas R., Tabor P.E., Wan K., Stapleton M., Sutton G.G., Venter C., RA Weinstock G., Scherer S.E., Myers E.W., Gibbs R.A., Rubin G.M.; RT "Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster RT euchromatic genome sequence."; RL Genome Biol. 3:RESEARCH0079-RESEARCH0079(2002). RN [3] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP GENOME REANNOTATION. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfied E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D., Drysdale R.A., Harris N.L., RA Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., RA Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537573; RA Kaminker J.S., Bergman C.M., Kronmiller B., Carlson J., Svirskas R., RA Patel S., Frise E., Wheeler D.A., Lewis S.E., Rubin G.M., Ashburner M., RA Celniker S.E.; RT "The transposable elements of the Drosophila melanogaster euchromatin: a RT genomics perspective."; RL Genome Biol. 3:RESEARCH0084-RESEARCH0084(2002). RN [5] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537574; RA Hoskins R.A., Smith C.D., Carlson J.W., Carvalho A.B., Halpern A., RA Kaminker J.S., Kennedy C., Mungall C.J., Sullivan B.A., Sutton G.G., RA Yasuhara J.C., Wakimoto B.T., Myers E.W., Celniker S.E., Rubin G.M., RA Karpen G.H.; RT "Heterochromatic sequences in a Drosophila whole-genome shotgun assembly."; RL Genome Biol. 3:RESEARCH0085-RESEARCH0085(2002). RN [6] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=16110336; DOI=10.1371/journal.pcbi.0010022; RA Quesneville H., Bergman C.M., Andrieu O., Autard D., Nouaud D., RA Ashburner M., Anxolabehere D.; RT "Combined evidence annotation of transposable elements in genome RT sequences."; RL PLoS Comput. Biol. 1:166-175(2005). RN [7] {ECO:0000313|EMBL:AAN09623.1} RP NUCLEOTIDE SEQUENCE. RG Berkeley Drosophila Genome Project; RA Celniker S., Carlson J., Wan K., Pfeiffer B., Frise E., George R., RA Hoskins R., Stapleton M., Pacleb J., Park S., Svirskas R., Smith E., Yu C., RA Rubin G.; RT "Drosophila melanogaster release 4 sequence."; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [8] {ECO:0000313|EMBL:AAN09623.1} RP NUCLEOTIDE SEQUENCE. RA Celniker S., Carlson J., Wan K., Frise E., Hoskins R., Park S., RA Svirskas R., Rubin G.; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [9] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=17569856; DOI=10.1126/science.1139815; RA Smith C.D., Shu S., Mungall C.J., Karpen G.H.; RT "The Release 5.1 annotation of Drosophila melanogaster heterochromatin."; RL Science 316:1586-1591(2007). RN [10] {ECO:0000313|EMBL:AAN09623.1, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=17569867; DOI=10.1126/science.1139816; RA Hoskins R.A., Carlson J.W., Kennedy C., Acevedo D., Evans-Holm M., RA Frise E., Wan K.H., Park S., Mendez-Lago M., Rossi F., Villasante A., RA Dimitri P., Karpen G.H., Celniker S.E.; RT "Sequence finishing and mapping of Drosophila melanogaster RT heterochromatin."; RL Science 316:1625-1628(2007). RN [11] {ECO:0000313|EMBL:ACS78060.1} RP NUCLEOTIDE SEQUENCE. RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.; RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases. RN [12] {ECO:0000313|EMBL:AAN09623.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=26109357; DOI=.1534/g3.115.018929; RG FlyBase Consortium; RA Matthews B.B., Dos Santos G., Crosby M.A., Emmert D.B., St Pierre S.E., RA Gramates L.S., Zhou P., Schroeder A.J., Falls K., Strelets V., Russo S.M., RA Gelbart W.M.; RT "Gene Model Annotations for Drosophila melanogaster: Impact of High- RT Throughput Data."; RL G3 (Bethesda) 5:1721-1736(2015). RN [13] {ECO:0000313|EMBL:AAN09623.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=26109356; DOI=.1534/g3.115.018937; RG FlyBase Consortium; RA Crosby M.A., Gramates L.S., Dos Santos G., Matthews B.B., St Pierre S.E., RA Zhou P., Schroeder A.J., Falls K., Emmert D.B., Russo S.M., Gelbart W.M.; RT "Gene Model Annotations for Drosophila melanogaster: The Rule-Benders."; RL G3 (Bethesda) 5:1737-1749(2015). RN [14] {ECO:0000313|EMBL:AAN09623.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=25589440; RA Hoskins R.A., Carlson J.W., Wan K.H., Park S., Mendez I., Galle S.E., RA Booth B.W., Pfeiffer B.D., George R.A., Svirskas R., Krzywinski M., RA Schein J., Accardo M.C., Damia E., Messina G., Mendez-Lago M., RA de Pablos B., Demakova O.V., Andreyeva E.N., Boldyreva L.V., Marra M., RA Carvalho A.B., Dimitri P., Villasante A., Zhimulev I.F., Rubin G.M., RA Karpen G.H., Celniker S.E.; RT "The Release 6 reference sequence of the Drosophila melanogaster genome."; RL Genome Res. 25:445-458(2015). RN [15] {ECO:0000313|EMBL:AAN09623.1} RP NUCLEOTIDE SEQUENCE. RG FlyBase; RL Submitted (APR-2020) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Key enzyme involved in DNA replication and DNA repair. CC Involved in Okazaki fragments processing by cleaving long flaps that CC escape FEN1: flaps that are longer than 27 nucleotides are coated by CC replication protein A complex (RPA), leading to recruit DNA2 which CC cleaves the flap until it is too short to bind RPA and becomes a CC substrate for FEN1. Also involved in 5'-end resection of DNA during CC double-strand break (DSB) repair by mediating the cleavage of 5'-ssDNA. CC {ECO:0000256|RuleBase:RU367041}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000256|ARBA:ARBA00001665, CC ECO:0000256|RuleBase:RU367041}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000256|ARBA:ARBA00001966}; CC -!- COFACTOR: CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000256|RuleBase:RU367041}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|RuleBase:RU367041}. CC Chromosome {ECO:0000256|RuleBase:RU367041}. CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. CC {ECO:0000256|ARBA:ARBA00007913, ECO:0000256|RuleBase:RU367041}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE014298; AAN09623.1; -; Genomic_DNA. DR EMBL; BT088860; ACS78060.1; -; mRNA. DR RefSeq; NP_727386.1; NM_167214.2. DR IntAct; Q8IRL9; 8. DR STRING; 7227.FBpp0071350; -. DR EnsemblMetazoa; FBtr0071415; FBpp0071350; FBgn0030170. DR GeneID; 31934; -. DR UCSC; CG2990-RB; d. melanogaster. DR FlyBase; FBgn0030170; CG2990. DR eggNOG; KOG1805; Eukaryota. DR GeneTree; ENSGT00940000165719; -. DR OrthoDB; 633768at2759; -. DR Reactome; R-DME-69166; Removal of the Flap Intermediate. DR BioGRID-ORCS; 31934; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 31934; -. DR Proteomes; UP000000803; Chromosome X. DR Bgee; FBgn0030170; Expressed in embryo and 24 other tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule. DR GO; GO:0043139; F:5'-3' DNA helicase activity; ISS:FlyBase. DR GO; GO:0017108; F:5'-flap endonuclease activity; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0017116; F:single-stranded DNA helicase activity; IEA:UniProtKB-UniRule. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0033567; P:DNA replication, Okazaki fragment processing; IEA:UniProtKB-UniRule. DR GO; GO:0071932; P:replication fork reversal; IBA:GO_Central. DR CDD; cd18808; SF1_C_Upf1; 1. DR InterPro; IPR026851; Dna2. DR InterPro; IPR041679; DNA2/NAM7-like_C. DR InterPro; IPR041677; DNA2/NAM7_AAA_11. DR InterPro; IPR014808; DNA_replication_fac_Dna2_N. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR10887:SF433; PTHR10887:SF433; 1. DR Pfam; PF13086; AAA_11; 2. DR Pfam; PF13087; AAA_12; 1. DR Pfam; PF08696; Dna2; 1. DR SUPFAM; SSF52540; SSF52540; 1. PE 1: Evidence at protein level; KW 4Fe-4S {ECO:0000256|RuleBase:RU367041}; KW ATP-binding {ECO:0000256|RuleBase:RU367041}; KW Chromosome {ECO:0000256|RuleBase:RU367041}; KW DNA damage {ECO:0000256|ARBA:ARBA00022763, ECO:0000256|RuleBase:RU367041}; KW DNA repair {ECO:0000256|ARBA:ARBA00023204, ECO:0000256|RuleBase:RU367041}; KW DNA replication {ECO:0000256|ARBA:ARBA00022705, KW ECO:0000256|RuleBase:RU367041}; KW DNA-binding {ECO:0000256|ARBA:ARBA00023125, ECO:0000256|RuleBase:RU367041}; KW Helicase {ECO:0000256|RuleBase:RU367041}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU367041}; KW Iron {ECO:0000256|RuleBase:RU367041}; KW Iron-sulfur {ECO:0000256|RuleBase:RU367041}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|RuleBase:RU367041}; KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268, KW ECO:0000256|RuleBase:RU367041}; Nuclease {ECO:0000256|RuleBase:RU367041}; KW Nucleotide-binding {ECO:0000256|RuleBase:RU367041}; KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|RuleBase:RU367041}; KW Proteomics identification {ECO:0000213|PeptideAtlas:Q8IRL9}; KW Reference proteome {ECO:0000313|Proteomes:UP000000803}. FT DOMAIN 101..297 FT /note="Dna2" FT /evidence="ECO:0000259|Pfam:PF08696" FT DOMAIN 637..731 FT /note="AAA_11" FT /evidence="ECO:0000259|Pfam:PF13086" FT DOMAIN 734..807 FT /note="AAA_11" FT /evidence="ECO:0000259|Pfam:PF13086" FT DOMAIN 815..1054 FT /note="AAA_12" FT /evidence="ECO:0000259|Pfam:PF13087" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 9..23 FT /note="Polar" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 1100 AA; 124589 MW; 45AB9774192C19FB CRC64; MATKRVLTPN ILENDNTDVT SSNPQKKFKE QLDFSSDEVE NIDWGDNDDF DLALIAAMDS ISNHRLELTK WQRCEVVRLE QLPNRKGLKV HVKRISGGDP ETADCQLLPP WNCMPMQVGD TVSLLGKWDP SAGCYVVDKE QGYCVSHPDF LISGTTVTGS LFCKRKSVLQ ERFRGLDSGN SVMVIGTLVH ELLQKVLRQK LFDKKHIQSA LQEMLASSSL AHLLYASNLI QVEMEDHLMK FIDPIVSFVA QYVKGEPPSV LLPEVYRGQI HEICDIEENL WVPQLGLKGK VDVSVKVKNQ RQREEIIPLE LKTGRASFSM EHKGQLLLYQ LMHSAQGRDT QSGLLLYLKE GLLREVASGR NEQRDLLMLR NDLAYWLTRE VAIPASKEDP LEQLPLPEPV YHHSACGNCA YNTICSSFAQ KDSSLQLSDS HPLKKLMPQL LEHLSEADHA YVQHWCGLLA LEEQHNRQSS HVRSFWTKDP AEREKEGIAI RHLKLVKGQE VILEEGRYRQ TLELGEEADP SRDLSLSGFD LGEYVVISST SRLAVAAGFI VSIEARRLDL RLERDLSQRY SEETFIIDKH DSQSFATFNF TNLGMLLSEG ERFQELRDII VAKKPPEQHK VLPKIILTKG APILLNLNKV QQNAALRALT TSSHLLIKGL PGTGKTQTLV ALVRLLHLLG KSVLITAQTH SAVDNLIMRL LPFGLPMMRL GSGSRIHKQL EEISEERLTK DCKTVEELEK ALGQPSIVGV TCLGCGHPLF QRRQFDYCIV DEATQVLQPT VLRPLIHCSK FVLVGDPEQL PPIVRSKEAR QRGADETLFQ RLDSEKATAV LSLQYRMNKT ITRLANELTY GGDLKCASDE VSGARFEVEL LNEAPRWVQR ALTTHLEQAV TLINTGDCLE RCQEFVYASQ RLVDTCSSIE QSFSEDKDEI RKLTSKKRVS KYTNYCEAGI VMHLLRYLLK SGYEASRIGV IAPYRAQVEL FKKLASKLDT DLECNTVDQF QGRDKNLIIY SCSKTGGDFS DMERSREAEI LEDQRRLTVA ITRAKNKLIL LGDIKCLEQY GPFRQLFKHI PDRCRLKLEE GRMEFGWQRI QEDLVGLMDT //