DNA2_XENLA
ID DNA2_XENLA Reviewed; 1053 AA.
AC Q8QHA5;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 79.
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; Synonyms=dna2l;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF LYS-655.
RC TISSUE=Oocyte;
RX PubMed=10636853; DOI=10.1074/jbc.275.3.1615;
RA Liu Q., Choe W.-C., Campbell J.L.;
RT "Identification of the Xenopus laevis homolog of Saccharomyces cerevisiae
RT DNA2 and its role in DNA replication.";
RL J. Biol. Chem. 275:1615-1624(2000).
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 by mediating the
CC cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the
CC presence of RPA. Also involved in DNA replication checkpoint
CC independently of Okazaki fragments processing (By similarity).
CC Possesses different enzymatic activities, such as single-stranded DNA
CC (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities.
CC While the ATPase and endonuclease activities are well-defined and play
CC a key role in Okazaki fragments processing and DSB repair, the 5'-3'
CC DNA helicase activity is subject to debate. According to various
CC reports, the helicase activity is weak and its function remains largely
CC unclear. Helicase activity may promote the motion of dna2 on the flap,
CC helping the nuclease function. {ECO:0000250,
CC ECO:0000269|PubMed:10636853}.
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Mitochondrion
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.
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DR EMBL; AF474372; AAL79550.1; -; mRNA.
DR RefSeq; NP_001079231.1; NM_001085762.1.
DR AlphaFoldDB; Q8QHA5; -.
DR SMR; Q8QHA5; -.
DR BioGRID; 97075; 1.
DR IntAct; Q8QHA5; 1.
DR PRIDE; Q8QHA5; -.
DR GeneID; 378492; -.
DR KEGG; xla:378492; -.
DR CTD; 378492; -.
DR Xenbase; XB-GENE-5829000; dna2.S.
DR OrthoDB; 633768at2759; -.
DR Proteomes; UP000186698; Chromosome 7S.
DR Bgee; 378492; Expressed in egg cell and 13 other tissues.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0017116; F:single-stranded DNA helicase activity; ISS:UniProtKB.
DR GO; GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; ISS:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0045002; P:double-strand break repair via single-strand annealing; IDA:CACAO.
DR GO; GO:0006264; P:mitochondrial DNA replication; ISS:UniProtKB.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISS:UniProtKB.
DR CDD; cd18808; SF1_C_Upf1; 1.
DR Gene3D; 3.40.50.300; -; 3.
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 1: Evidence at protein level;
KW 4Fe-4S; ATP-binding; DNA damage; DNA repair; DNA replication; DNA-binding;
KW Endonuclease; Helicase; Hydrolase; Iron; Iron-sulfur; Metal-binding;
KW Mitochondrion; Multifunctional enzyme; Nuclease; Nucleotide-binding;
KW Nucleus; Reference proteome.
FT CHAIN 1..1053
FT /note="DNA replication ATP-dependent helicase/nuclease
FT DNA2"
FT /id="PRO_0000263606"
FT REGION 86..521
FT /note="Nuclease activity"
FT /evidence="ECO:0000250"
FT REGION 522..1053
FT /note="Helicase activity"
FT /evidence="ECO:0000250"
FT BINDING 142
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 395
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 404
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 649..656
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MUTAGEN 655
FT /note="K->E: Loss of ATPase activity in vitro."
FT /evidence="ECO:0000269|PubMed:10636853"
SQ SEQUENCE 1053 AA; 119732 MW; DB08973372DFA9EF CRC64;
MEPVSAECHL PPEDDLLEMM MEQSFTEPEE KSQDKPTRKI IPKTKLCKGV NNRYCVLHIK
EVYAQREEKH LTITASQEGD DLELCILKDD WVALQIKPGD IIHLEGNCSV DNTWTISRDT
GYLILYPDLL ISGTSIANGI RCLRRSVLSE KFKVCDKGSR QMLNGTMLHD IFQRATTCGF
TDSVLQELAH HTVHGPKYLK EMYQLKLNQA DVMGEIQEYL PSLSKWATDF MTHPLNQQQI
NRTKSTAGDP TETTKVSEFL DIEENIWSPR FGLKGKIDVT ARVKIHQKSK AHLKIMPLEL
KTGKESNSIE HRSQVVLYTL LSQERREDPE AGLLLYLKTG NMYTVPGNRL DRRELLKIRN
ELSYYLTNVL HKSDNGSKET TLASLPAMIA DRQACKYCSQ MRNCALYNRS VEQQTENCYI
PPEMIPVVQK ETEHLTEDHL QYFRLWYLMC TLEANSKDSK MGRKNIWMMS SSEREEDGQC
IGNLIRTGHV QTISDVQYLH SFQRRSGSVP ATNLASGDRV VVSGEERFLA LSTGYIKEVK
DENITCILDR SLVKLPEDLL FRLDHEEGGG GLEFHLGNLS RLMENSSVSE KLRKLIIDFS
KPNFVQHLSS ILPPDAKDIV ASILRGLNKP QKQAMKRVLL SKDYTLIVGM PGTGKTTTIC
TLVRILYACG FSVLLTSYTH SAVDNILLKL KKFQVGFLRL GRTQKLHPDV QEFSEEEICK
AKSIKSLSAL EELYNSQPVV ATTCMGVNHP IFTRRRFDFC IVDEASQISQ PICLGPLFFA
DRFVLVGDHQ QLPPLVKSAE ARELGMSESL FKRLERNQEA VVQLTVQYRM NSKIMALSNK
LVYEGRLECA SDRVSNAVVQ LPHIKTLLLE LEFRESQESM WIKDVLEPSN PVCFLNTEKI
PALETEEKGG ISNWIEAKLV FHLTKLYLKA GCRPSDIGII APYRQQLKMI SNYFNSLSAS
AVEVNTVDKY QGRDKSVIIV SFVRSNIDGK LGDLLKDWRR LNVALTRAKH KLIMLGCVPT
LNRFDCLEQL ICNLKTENQI YDLPEGAHEH FPV
