DNA2_RAT
ID DNA2_RAT Reviewed; 1059 AA.
AC D3ZG52;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=DNA replication ATP-dependent helicase/nuclease DNA2;
DE AltName: Full=DNA replication ATP-dependent helicase-like homolog;
DE Includes:
DE RecName: Full=DNA replication nuclease DNA2;
DE EC=3.1.-.-;
DE Includes:
DE RecName: Full=DNA replication ATP-dependent helicase DNA2;
DE EC=3.6.4.12;
GN Name=Dna2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: Key enzyme involved in DNA replication and DNA repair in
CC nucleus and mitochondrion. Involved in Okazaki fragments processing by
CC cleaving long flaps that escape FEN1: flaps that are longer than 27
CC nucleotides are coated by replication protein A complex (RPA), leading
CC to recruit DNA2 which cleaves the flap until it is too short to bind
CC RPA and becomes a substrate for FEN1. Also involved in 5'-end resection
CC of DNA during double-strand break (DSB) repair: recruited by BLM and
CC mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is
CC prevented by the presence of RPA. Also involved in DNA replication
CC checkpoint independently of Okazaki fragments processing. Possesses
CC different enzymatic activities, such as single-stranded DNA (ssDNA)-
CC dependent ATPase, 5'-3' helicase and endonuclease activities. While the
CC ATPase and endonuclease activities are well-defined and play a key role
CC in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase
CC activity is subject to debate. According to various reports, the
CC helicase activity is weak and its function remains largely unclear.
CC Helicase activity may promote the motion of DNA2 on the flap, helping
CC the nuclease function (By similarity). {ECO:0000250}.
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 -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250};
CC -!- SUBUNIT: Interacts with BLM and WDHD1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Mitochondrion
CC {ECO:0000250}.
CC -!- PTM: Acetylated by EP300, leading to stimulate the 5'-3' endonuclease,
CC the 5'-3' helicase and DNA-dependent ATPase activities, possibly by
CC increasing DNA substrate affinity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.
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DR AlphaFoldDB; D3ZG52; -.
DR SMR; D3ZG52; -.
DR STRING; 10116.ENSRNOP00000000438; -.
DR PaxDb; D3ZG52; -.
DR PeptideAtlas; D3ZG52; -.
DR PRIDE; D3ZG52; -.
DR UCSC; RGD:1306791; rat.
DR RGD; 1306791; Dna2.
DR eggNOG; KOG1805; Eukaryota.
DR HOGENOM; CLU_001666_2_0_1; -.
DR InParanoid; D3ZG52; -.
DR PhylomeDB; D3ZG52; -.
DR TreeFam; TF314903; -.
DR Reactome; R-RNO-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-RNO-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-RNO-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-RNO-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-RNO-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-RNO-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-RNO-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-69166; Removal of the Flap Intermediate.
DR Reactome; R-RNO-69473; G2/M DNA damage checkpoint.
DR PRO; PR:D3ZG52; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0042645; C:mitochondrial nucleoid; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0043139; F:5'-3' DNA helicase activity; ISS:UniProtKB.
DR GO; GO:0017108; F:5'-flap endonuclease activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003678; F:DNA helicase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004518; F:nuclease activity; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0017116; F:single-stranded DNA helicase activity; ISS:UniProtKB.
DR GO; GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; ISO:RGD.
DR GO; GO:0006284; P:base-excision repair; ISO:RGD.
DR GO; GO:0000729; P:DNA double-strand break processing; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; ISS:UniProtKB.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0033567; P:DNA replication, Okazaki fragment processing; ISS:UniProtKB.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; ISO:RGD.
DR GO; GO:0043504; P:mitochondrial DNA repair; ISO:RGD.
DR GO; GO:0006264; P:mitochondrial DNA replication; ISO:RGD.
DR GO; GO:1902990; P:mitotic telomere maintenance via semi-conservative replication; ISO:RGD.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISO:RGD.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:RGD.
DR GO; GO:0071932; P:replication fork reversal; IBA:GO_Central.
DR GO; GO:0000723; P:telomere maintenance; ISO:RGD.
DR CDD; cd18808; SF1_C_Upf1; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR Gene3D; 3.90.320.10; -; 1.
DR InterPro; IPR026851; Dna2.
DR InterPro; IPR045055; DNA2/NAM7-like.
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 InterPro; IPR011604; PDDEXK-like_dom_sf.
DR PANTHER; PTHR10887; PTHR10887; 1.
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 3: Inferred from homology;
KW 4Fe-4S; Acetylation; ATP-binding; DNA damage; DNA repair; DNA replication;
KW DNA-binding; Endonuclease; Helicase; Hydrolase; Iron; Iron-sulfur;
KW Metal-binding; Mitochondrion; Multifunctional enzyme; Nuclease;
KW Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..1059
FT /note="DNA replication ATP-dependent helicase/nuclease
FT DNA2"
FT /id="PRO_0000419466"
FT REGION 82..519
FT /note="Nuclease activity"
FT /evidence="ECO:0000250"
FT REGION 520..1059
FT /note="Helicase activity"
FT /evidence="ECO:0000250"
FT BINDING 137
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 394
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 397
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 403
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 648..655
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1059 AA; 119588 MW; AAFC221E6785C5AF CRC64;
MEPLDDLDLL LLEEDSGAEA VPRMEILQKK ADAFFAETVL SRGVDNRYLV LAVETKLNER
GAEEKHLLIT VSQEGEQEVL CILRNGWSSV PVEPGDIIHI EGDCTSEPWI VDDDFGYFIL
SPDMLISGTS VASSIRCLRR AVLSETFRVS DTATRQMLIG TILHEVFQKA ISESFAPEKL
QELALQTLRE VRHLKEMYRL NLSQDEVRCE VEEYLPSFSK WADEFMHKGT KAEFPQMHLS
LPSDSSDRSS PCNIEVVKSL DIEESIWSPR FGLKGKIDVT VGVKIHRDCK TKYKIMPLEL
KTGKESNSIE HRGQVILYTL LSQERREDPE AGWLLYLKTG QMYPVPANHL DKRELLKLRN
QLAFSLLHRV SRAAAGEEAR LLALPQIIEE EKTCKYCSQM GNCALYSRAV EQVHDTSIPE
GMRSKIQEGT QHLTRAHLKY FSLWCLMLTL ESQSKDTKKS HQSIWLTPAS KLEESGNCIG
SLVRTEPVKR VCDGHYLHNF QRKNGPMPAT NLMAGDRIIL SGEERKLFAL SKGYVKRIDT
AAVTCLLDRN LSTLPETTLF RLDREEKHGD INTPLGNLSK LMENTDSSKR LRELIIDFKE
PQFIAYLSSV LPHDAKDTVA NILKGLNKPQ RQAMKKVLLS KDYTLIVGMP GTGKTTTICA
LVRILSACGF SVLLTSYTHS AVDNILLKLA KFKIGFLRLG QSHKVHPDIQ KFTEEEMCRL
RSIASLAHLE ELYNSHPVVA TTCMGISHPM FSRKTFDFCI VDEASQISQP ICLGPLFFSR
RFVLVGDHKQ LPPLVLNREA RALGMSESLF KRLERNESAV VQLTIQYRMN RKIMSLSNKL
TYEGKLECGS DRVANAVITL PNLKDVRLEF YADYSDNPWL AGVFEPDNPV CFLNTDKVPA
PEQIENGGVS NVTEARLIVF LTSTFIKAGC SPSDIGIIAP YRQQLRTITD LLARSSVGMV
EVNTVDKYQG RDKSLILVSF VRSNEDGTLG ELLKDWRRLN VAITRAKHKL ILLGSVSSLK
RFPPLEKLFD HLNAEQLISN LPSREHESLY HILGDCQRD
