DNA2_SCHPO
ID DNA2_SCHPO Reviewed; 1397 AA.
AC Q9URU2; O74241; Q9UTT6; Q9UUK8;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=DNA replication ATP-dependent helicase/nuclease dna2;
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; ORFNames=SPBC16D10.04c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RX PubMed=10880469; DOI=10.1093/genetics/155.3.1055;
RA Kang H.-Y., Choi E., Bae S.-H., Lee K.-H., Gim B.-S., Kim H.-D., Park C.,
RA MacNeill S.A., Seo Y.-S.;
RT "Genetic analyses of Schizosaccharomyces pombe dna2+ reveal that dna2 plays
RT an essential role in Okazaki fragment metabolism.";
RL Genetics 155:1055-1067(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP REVISION OF GENE MODEL.
RX PubMed=21511999; DOI=10.1126/science.1203357;
RA Rhind N., Chen Z., Yassour M., Thompson D.A., Haas B.J., Habib N.,
RA Wapinski I., Roy S., Lin M.F., Heiman D.I., Young S.K., Furuya K., Guo Y.,
RA Pidoux A., Chen H.M., Robbertse B., Goldberg J.M., Aoki K., Bayne E.H.,
RA Berlin A.M., Desjardins C.A., Dobbs E., Dukaj L., Fan L., FitzGerald M.G.,
RA French C., Gujja S., Hansen K., Keifenheim D., Levin J.Z., Mosher R.A.,
RA Mueller C.A., Pfiffner J., Priest M., Russ C., Smialowska A., Swoboda P.,
RA Sykes S.M., Vaughn M., Vengrova S., Yoder R., Zeng Q., Allshire R.,
RA Baulcombe D., Birren B.W., Brown W., Ekwall K., Kellis M., Leatherwood J.,
RA Levin H., Margalit H., Martienssen R., Nieduszynski C.A., Spatafora J.W.,
RA Friedman N., Dalgaard J.Z., Baumann P., Niki H., Regev A., Nusbaum C.;
RT "Comparative functional genomics of the fission yeasts.";
RL Science 332:930-936(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 120-140, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=ATCC 38364 / 968;
RX PubMed=10759889; DOI=10.1046/j.1365-2443.2000.00317.x;
RA Ding D.-Q., Tomita Y., Yamamoto A., Chikashige Y., Haraguchi T.,
RA Hiraoka Y.;
RT "Large-scale screening of intracellular protein localization in living
RT fission yeast cells by the use of a GFP-fusion genomic DNA library.";
RL Genes Cells 5:169-190(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1053-1243.
RC STRAIN=972 / ATCC 24843;
RX PubMed=9649516; DOI=10.1093/genetics/149.3.1221;
RA Gould K.L., Burns C.G., Feoktistova A., Hu C.-P., Pasion S.G.,
RA Forsburg S.L.;
RT "Fission yeast cdc24(+) encodes a novel replication factor required for
RT chromosome integrity.";
RL Genetics 149:1221-1233(1998).
RN [6]
RP FUNCTION.
RX PubMed=15302919; DOI=10.1093/nar/gkh720;
RA Ryu G.H., Tanaka H., Kim D.H., Kim J.H., Bae S.H., Kwon Y.N., Rhee J.S.,
RA MacNeill S.A., Seo Y.S.;
RT "Genetic and biochemical analyses of Pfh1 DNA helicase function in fission
RT yeast.";
RL Nucleic Acids Res. 32:4205-4216(2004).
RN [7]
RP FUNCTION, AND TELOMERE-BINDING.
RX PubMed=15485922; DOI=10.1128/mcb.24.21.9557-9567.2004;
RA Tomita K., Kibe T., Kang H.Y., Seo Y.S., Uritani M., Ushimaru T., Ueno M.;
RT "Fission yeast Dna2 is required for generation of the telomeric single-
RT strand overhang.";
RL Mol. Cell. Biol. 24:9557-9567(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH CDC24.
RX PubMed=15576681; DOI=10.1093/nar/gkh963;
RA Tanaka H., Ryu G.H., Seo Y.S., MacNeill S.A.;
RT "Genetics of lagging strand DNA synthesis and maturation in fission yeast:
RT suppression analysis links the Dna2-Cdc24 complex to DNA polymerase
RT delta.";
RL Nucleic Acids Res. 32:6367-6377(2004).
RN [9]
RP FUNCTION.
RX PubMed=15915339; DOI=10.1007/s00294-005-0584-2;
RA Tsutsui Y., Morishita T., Natsume T., Yamashita K., Iwasaki H., Yamao F.,
RA Shinagawa H.;
RT "Genetic and physical interactions between Schizosaccharomyces pombe Mcl1
RT and Rad2, Dna2 and DNA polymerase alpha: evidence for a multifunctional
RT role of Mcl1 in DNA replication and repair.";
RL Curr. Genet. 48:34-43(2005).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT SER-134 AND SER-219, AND MUTAGENESIS OF
RP SER-219; GLU-559 AND LYS-960.
RX PubMed=22682245; DOI=10.1016/j.cell.2012.04.030;
RA Hu J., Sun L., Shen F., Chen Y., Hua Y., Liu Y., Zhang M., Hu Y., Wang Q.,
RA Xu W., Sun F., Ji J., Murray J.M., Carr A.M., Kong D.;
RT "The intra-s phase checkpoint targets dna2 to prevent stalled replication
RT forks from reversing.";
RL Cell 149:1221-1232(2012).
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. Is a target of the intra-S phase checkpoint,
CC associating with stalled replication forks when phosphorylated at Ser-
CC 219 and preventing the stalled replication forks from reversing. Also
CC involved in 5'-end resection of DNA during double-strand break (DSB)
CC repair by mediating the cleavage of 5'-ssDNA. Also required for the
CC production of G-rich single-strand overhangs at telomere ends and thus
CC in telomere length maintenance. Possesses different enzymatic
CC activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3'
CC helicase and endonuclease activities. While the ATPase and endonuclease
CC activities are well-defined and play a key role in Okazaki fragments
CC processing and DSB repair, the 5'-3' DNA helicase activity is atypical:
CC it cannot load onto its tracking strand internally and has an absolute
CC free 5'-end requirement. Helicase activity may promote the motion of
CC dna2 on the flap, helping the nuclease function.
CC {ECO:0000269|PubMed:15302919, ECO:0000269|PubMed:15485922,
CC ECO:0000269|PubMed:15576681, ECO:0000269|PubMed:15915339,
CC ECO:0000269|PubMed:22682245}.
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 cdc1, cdc24 and rad2.
CC {ECO:0000269|PubMed:15576681}.
CC -!- INTERACTION:
CC Q9URU2; O75004: cdc24; NbExp=3; IntAct=EBI-16120355, EBI-1559355;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Chromosome, telomere.
CC Note=Recruited to double-strand. break (DSB) sites.
CC -!- PTM: Phosphorylated at Ser-219 by cds1/check2, leading to association
CC with stalled replication forks. {ECO:0000269|PubMed:22682245}.
CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.
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; AF144384; AAD38528.1; -; Genomic_DNA.
DR EMBL; CU329671; CAB38508.2; -; Genomic_DNA.
DR EMBL; AB028014; BAA87318.1; -; Genomic_DNA.
DR EMBL; AF075169; AAC39502.1; -; Genomic_DNA.
DR PIR; T39568; T39568.
DR PIR; T47242; T47242.
DR PIR; T51292; T51292.
DR RefSeq; NP_596499.2; NM_001022420.2.
DR AlphaFoldDB; Q9URU2; -.
DR SMR; Q9URU2; -.
DR BioGRID; 276685; 19.
DR DIP; DIP-61017N; -.
DR IntAct; Q9URU2; 3.
DR STRING; 4896.SPBC16D10.04c.1; -.
DR iPTMnet; Q9URU2; -.
DR MaxQB; Q9URU2; -.
DR PaxDb; Q9URU2; -.
DR PRIDE; Q9URU2; -.
DR EnsemblFungi; SPBC16D10.04c.1; SPBC16D10.04c.1:pep; SPBC16D10.04c.
DR GeneID; 2540148; -.
DR KEGG; spo:SPBC16D10.04c; -.
DR PomBase; SPBC16D10.04c; dna2.
DR VEuPathDB; FungiDB:SPBC16D10.04c; -.
DR eggNOG; KOG1805; Eukaryota.
DR HOGENOM; CLU_001666_2_1_1; -.
DR InParanoid; Q9URU2; -.
DR OMA; NYCEAAI; -.
DR Reactome; R-SPO-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-SPO-69166; Removal of the Flap Intermediate.
DR PRO; PR:Q9URU2; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0140445; C:chromosome, telomeric repeat region; IDA:PomBase.
DR GO; GO:0005737; C:cytoplasm; IDA:PomBase.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0043596; C:nuclear replication fork; IDA:PomBase.
DR GO; GO:0005654; C:nucleoplasm; IDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:PomBase.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:1990601; F:5' overhang single-stranded DNA endodeoxyribonuclease activity; IDA:PomBase.
DR GO; GO:0017108; F:5'-flap endonuclease activity; ISO:PomBase.
DR GO; GO:0005524; F:ATP binding; ISM:PomBase.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003682; F:chromatin binding; IDA:PomBase.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004518; F:nuclease activity; IMP:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0045145; F:single-stranded DNA 5'-3' exodeoxyribonuclease activity; IDA:PomBase.
DR GO; GO:0017116; F:single-stranded DNA helicase activity; IEA:InterPro.
DR GO; GO:0006281; P:DNA repair; ISS:PomBase.
DR GO; GO:1903461; P:Okazaki fragment processing involved in mitotic DNA replication; IMP:PomBase.
DR GO; GO:1903469; P:removal of RNA primer involved in mitotic DNA replication; IC:PomBase.
DR GO; GO:0031297; P:replication fork processing; IMP:PomBase.
DR GO; GO:0071932; P:replication fork reversal; IMP:UniProtKB.
DR GO; GO:0072429; P:response to intra-S DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0031860; P:telomeric 3' overhang formation; IGI:PomBase.
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; IPR022765; Dna2/Cas4_DUF83.
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; PF01930; Cas_Cas4; 1.
DR Pfam; PF08696; Dna2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; ATP-binding; Chromosome; Cytoplasm; DNA damage; DNA repair;
KW DNA replication; DNA-binding; Endonuclease; Helicase; Hydrolase; Iron;
KW Iron-sulfur; Metal-binding; Multifunctional enzyme; Nuclease;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Telomere.
FT CHAIN 1..1397
FT /note="DNA replication ATP-dependent helicase/nuclease
FT dna2"
FT /id="PRO_0000080710"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..808
FT /note="Nuclease activity"
FT /evidence="ECO:0000250"
FT REGION 809..1397
FT /note="Helicase activity"
FT /evidence="ECO:0000250"
FT BINDING 450
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 679
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 682
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 688
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 954..961
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22682245"
FT MOD_RES 219
FT /note="Phosphoserine; by CHEK2"
FT /evidence="ECO:0000269|PubMed:22682245"
FT MUTAGEN 219
FT /note="S->A: Impaired phosphorylation by cds1/check2,
FT leading to stalled fork reversing."
FT /evidence="ECO:0000269|PubMed:22682245"
FT MUTAGEN 219
FT /note="S->D: Mimics phosphorylation; not able to rescue
FT hydroxyurea-sensitivity in cds1 mutant cells."
FT /evidence="ECO:0000269|PubMed:22682245"
FT MUTAGEN 559
FT /note="E->A: Not able to complement a dna2(ts) mutant at
FT restrictive temperature of 36 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:22682245"
FT MUTAGEN 960
FT /note="K->T: Able to complement a dna2(ts) mutant at
FT restrictive temperature of 36 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:22682245"
SQ SEQUENCE 1397 AA; 157659 MW; 5BE34210382E4B8C CRC64;
MFNDQSKTTS SVKGICATTD NNHGNLKKTN STPFRKNYLL NGRTKLKLEN FAYNASTEIS
SPKISEKKHS SLPIKRKNTF NESSTSFSPF TKAHKEITDD LKPDKSFTRK SDLNSQDMPV
CFQETSKDLC RSSSTQHLLD HQTTDSTIID MKPVSTNSKS DVFTLYTDET VLLRRCASDN
KPLINNNLSS SNVSENQSRS FGSYDEVKNQ GNNLHKVPSL VSIIRNARSS EQSRIAANSS
CLLKGSDTEI DEDDFALEAE DLAALDSLER QYSQLPNSTV TASAKDIEKT AKVNHVGGDL
QSYCSATKAS DATINEEPVN LALDKACNSL PDINSDFIDD WDDSCDGCTP GELCEFSSEY
TVLEVHEDFI FHEGNHFRQL KLILEANDIL HQLFLRGDWT ETSIFVGDSI RVEATFDKDN
TAIVDNDKGL IIIHPKILMS ATAVASSFPC LRKAVISDRV GIYGPPTKAM VTGNILHDFF
QHALYRGIDA LENVDINLET SIKTYISDIY FADLSLDEIR EELDARLPLL KSIVERYLIS
KKNDNNNESI HISRLLDIEE SIWSPRFGLK GNIDATVEVV LTEKPESSST LTLPLELKTG
RYVDNISHFA QSLLYTLLIS DRYGINTNQA LLCYLENSTI KNLVASNSQL RGLIMTRNSL
AQHNFRRSLP EMISNRKICD HCSLVSECLF FQKMSDKGVA NSNGLTESWN EWMREVKDED
LEFYKKWEKL LNQEERLLLL KRGDVLTFDT EELEAYGKTL YPLYITKEDI VCLEIDDRVF
HYKFAFLNDN GYPRNFLHSG FSVGERVFIS DEHGHWSLAK GHIVHIQDSC IEVRTRHRLH
IPWLKMPNFD FKKNQVFFGN YEDSKLSFIG SNHTRYRIDK DEFSSGIASI RGTLMSSVLP
DAPLIIRDMI IRLKPPKFCN SALIDPEFLK CLNEDQITAL KKCHAAEHYS LILGMPGTGK
TTTISSLIRS LLAKKKKILL TSFTHLAVDN ILIKLKGCDS TIVRLGSPHK IHPLVKEFCL
TEGTTFDDLA SLKHFYEDPQ IVACSSLGVY HSIFNKRKFD YCIIDEASQI PLPICLGPLQ
LAEKFVLVGD HYQLPPLVKN SRTSKDGLSL SLFKLLSEKH PEAVTTLRLQ YRMNEDINSL
SSELIYGGNL VCGSKTISQK KLILPKAHLS DGLPDSSSSL HWVNKLINPS HSVIFFNTDD
ILGVESKTNN ILENHTEAFL IEQAVSSFLE RGVKQSSIGI ISIYKSQVEL LSKNLKSFTE
IEINTVDRYQ GRDKDIILIS FVRSNSKNLV GELLRDWHRL NVALSRAKVK CIMFGSLSTL
SSSNIVSHLL KLLEKNKWIF TLNENDIATK FDENSSPIKD CSQVATTNNA KVIIRKNQRF
FNSDNLCEKA ILPQLEF
