WRNXO_DROME
ID WRNXO_DROME Reviewed; 353 AA.
AC Q9VE86; A7L742; B6IDR2; Q961E1;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=3'-5' exonuclease {ECO:0000303|PubMed:18346216};
DE EC=3.1.11.-;
DE AltName: Full=Werner Syndrome-like exonuclease;
DE Short=DmWRNexo {ECO:0000303|PubMed:18346216};
GN Name=WRNexo {ECO:0000312|FlyBase:FBgn0038608}; ORFNames=CG7670;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ABS71855.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18346216; DOI=10.1111/j.1474-9726.2008.00388.x;
RA Saunders R.D., Boubriak I., Clancy D.J., Cox L.S.;
RT "Identification and characterization of a Drosophila ortholog of WRN
RT exonuclease that is required to maintain genome integrity.";
RL Aging Cell 7:418-425(2008).
RN [2] {ECO:0000312|EMBL:AAF55541.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., 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.A., 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.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., 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.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAF55541.2}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., 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:0000312|EMBL:AAK93071.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Ovary {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5] {ECO:0000312|EMBL:ACJ13209.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION.
RX PubMed=18056975; DOI=10.1196/annals.1404.009;
RA Cox L.S., Clancy D.J., Boubriak I., Saunders R.D.;
RT "Modeling Werner Syndrome in Drosophila melanogaster: hyper-recombination
RT in flies lacking WRN-like exonuclease.";
RL Ann. N. Y. Acad. Sci. 1119:274-288(2007).
RN [7] {ECO:0000305}
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103; SER-109 AND SER-111, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo {ECO:0000269|PubMed:18327897};
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-162; GLU-164 AND ASP-229.
RX PubMed=18956248; DOI=10.1007/s10522-008-9181-3;
RA Boubriak I., Mason P.A., Clancy D.J., Dockray J., Saunders R.D., Cox L.S.;
RT "DmWRNexo is a 3'-5' exonuclease: phenotypic and biochemical
RT characterization of mutants of the Drosophila orthologue of human WRN
RT exonuclease.";
RL Biogerontology 10:267-277(2009).
CC -!- FUNCTION: Has exonuclease activity on both single-stranded and duplex
CC templates bearing overhangs, but not blunt ended duplex DNA, and
CC cleaves in a 3'-5' direction (PubMed:18346216, PubMed:18056975,
CC PubMed:18956248). Essential for the formation of DNA replication focal
CC centers (PubMed:18346216, PubMed:18956248). Has an important role in
CC maintaining genome stability (PubMed:18346216, PubMed:18956248).
CC {ECO:0000269|PubMed:18056975, ECO:0000269|PubMed:18346216,
CC ECO:0000269|PubMed:18956248}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18956248}.
CC -!- DISRUPTION PHENOTYPE: Females are sterile. Hypersensitive to the
CC topoisomerase I inhibitor camptothecin. Highly elevated rates of
CC mitotic DNA recombination resulting from excessive reciprocal exchange.
CC {ECO:0000269|PubMed:18346216, ECO:0000269|PubMed:18956248}.
CC -!- SIMILARITY: Belongs to the WRNexo family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACJ13209.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EF680279; ABS71854.1; -; mRNA.
DR EMBL; EF680280; ABS71855.1; -; mRNA.
DR EMBL; AE014297; AAF55541.2; -; Genomic_DNA.
DR EMBL; AY051647; AAK93071.1; -; mRNA.
DR EMBL; BT050502; ACJ13209.1; ALT_INIT; mRNA.
DR RefSeq; NP_001163646.1; NM_001170175.2.
DR RefSeq; NP_650715.3; NM_142458.4.
DR AlphaFoldDB; Q9VE86; -.
DR SMR; Q9VE86; -.
DR BioGRID; 67224; 6.
DR IntAct; Q9VE86; 3.
DR STRING; 7227.FBpp0291513; -.
DR iPTMnet; Q9VE86; -.
DR PaxDb; Q9VE86; -.
DR DNASU; 42208; -.
DR EnsemblMetazoa; FBtr0083586; FBpp0083007; FBgn0038608.
DR GeneID; 42208; -.
DR KEGG; dme:Dmel_CG7670; -.
DR UCSC; CG7670-RA; d. melanogaster.
DR CTD; 42208; -.
DR FlyBase; FBgn0038608; WRNexo.
DR VEuPathDB; VectorBase:FBgn0038608; -.
DR eggNOG; KOG4373; Eukaryota.
DR InParanoid; Q9VE86; -.
DR PhylomeDB; Q9VE86; -.
DR BioGRID-ORCS; 42208; 0 hits in 1 CRISPR screen.
DR ChiTaRS; WRNexo; fly.
DR GenomeRNAi; 42208; -.
DR PRO; PR:Q9VE86; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038608; Expressed in secondary oocyte and 30 other tissues.
DR ExpressionAtlas; Q9VE86; baseline and differential.
DR Genevisible; Q9VE86; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IMP:UniProtKB.
DR GO; GO:0008311; F:double-stranded DNA 3'-5' exodeoxyribonuclease activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0008310; F:single-stranded DNA 3'-5' exodeoxyribonuclease activity; IDA:FlyBase.
DR GO; GO:0000738; P:DNA catabolic process, exonucleolytic; IDA:FlyBase.
DR GO; GO:0045950; P:negative regulation of mitotic recombination; IMP:FlyBase.
DR GO; GO:0048478; P:replication fork protection; IGI:FlyBase.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR002562; 3'-5'_exonuclease_dom.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF01612; DNA_pol_A_exo1; 1.
DR SMART; SM00474; 35EXOc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW Exonuclease; Hydrolase; Magnesium; Metal-binding; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..353
FT /note="3'-5' exonuclease"
FT /id="PRO_0000399376"
FT DOMAIN 145..313
FT /note="3'-5' exonuclease"
FT /evidence="ECO:0000255"
FT REGION 1..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 162
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18956248"
FT BINDING 162
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18956248"
FT BINDING 164
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18956248"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 162
FT /note="D->A: Completely lacks exonuclease activity, when
FT associated with A-164."
FT /evidence="ECO:0000269|PubMed:18956248"
FT MUTAGEN 164
FT /note="E->A: Completely lacks exonuclease activity, when
FT associated with A-162."
FT /evidence="ECO:0000269|PubMed:18956248"
FT MUTAGEN 229
FT /note="D->V: 20-fold increase in levels of mitotic
FT recombination, very limited 3'-5' exonuclease activity."
FT /evidence="ECO:0000269|PubMed:18956248"
FT CONFLICT 78
FT /note="V -> VK (in Ref. 1; ABS71854)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="D -> A (in Ref. 4; AAK93071)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 353 AA; 40293 MW; CA608DB630678EE6 CRC64;
MEKYLTKMPI KSKANEVPKE EAGVKKETPK VARKATKKDT PKELKDKENA GDDNTPKQTK
GRPGRPAAKR KNLDTPDVTE KLAMEEENPP KRRSSRLTRS TRSMAEDGSP SPEKEKPEKL
PFIKYKGAIK YFTESQDIAA SADDVLQWVE KQKDEVVPMA FDMEWPFSFQ TGPGKSAVIQ
ICVDEKCCYI YQLTNVKKLP AALVALINHP KVRLHGVNIK NDFRKLARDF PEVTAEPLIE
KCVDLGLWCN EVCETGGRWS LERLTNFIAK KAMDKSKKVR MSKWHVIPLD ENQLMYAAID
VYIGQVIYRE LERREKVKIK NEEEFKEKNG DAAFKAMKAL GETFLTKINE VTL
