EXD2_DROME
ID EXD2_DROME Reviewed; 583 AA.
AC Q9VGN7;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Exonuclease 3'-5' domain-containing protein 2;
DE Short=dEXD2 {ECO:0000303|PubMed:29335528};
DE EC=3.1.13.- {ECO:0000269|PubMed:29335528};
GN Name=Exd2 {ECO:0000312|FlyBase:FBgn0037901};
GN ORFNames=CG6744 {ECO:0000312|FlyBase:FBgn0037901};
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]
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 [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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Testis;
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 [4]
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=29335528; DOI=10.1038/s41556-017-0016-9;
RA Silva J., Aivio S., Knobel P.A., Bailey L.J., Casali A., Vinaixa M.,
RA Garcia-Cao I., Coyaud E., Jourdain A.A., Perez-Ferreros P., Rojas A.M.,
RA Antolin-Fontes A., Samino-Gene S., Raught B., Gonzalez-Reyes A.,
RA Ribas de Pouplana L., Doherty A.J., Yanes O., Stracker T.H.;
RT "EXD2 governs germ stem cell homeostasis and lifespan by promoting
RT mitoribosome integrity and translation.";
RL Nat. Cell Biol. 20:162-174(2018).
CC -!- FUNCTION: 3'-5' exoribonuclease required for mitochondrial metabolism.
CC {ECO:0000269|PubMed:18056975, ECO:0000269|PubMed:29335528}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9NVH0};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9NVH0};
CC Note=Divalent metal cations; Mg(2+) or Mn(2+).
CC {ECO:0000250|UniProtKB:Q9NVH0};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9NVH0}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Developmental delays and premature female
CC germline stem cell attrition, reduced fecundity, associated with a
CC dramatic extension of lifespan that is reversed with an antioxidant
CC diet. {ECO:0000269|PubMed:29335528}.
CC -!- SIMILARITY: Belongs to the EXD2 family. {ECO:0000305}.
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DR EMBL; AE014297; AAF54639.2; -; Genomic_DNA.
DR EMBL; AE014297; AFH06366.1; -; Genomic_DNA.
DR EMBL; AY089433; AAL90171.1; -; mRNA.
DR RefSeq; NP_001247048.1; NM_001260119.2.
DR RefSeq; NP_650075.1; NM_141818.2.
DR AlphaFoldDB; Q9VGN7; -.
DR SMR; Q9VGN7; -.
DR DIP; DIP-23707N; -.
DR IntAct; Q9VGN7; 2.
DR STRING; 7227.FBpp0081878; -.
DR PaxDb; Q9VGN7; -.
DR PRIDE; Q9VGN7; -.
DR DNASU; 41374; -.
DR EnsemblMetazoa; FBtr0082402; FBpp0081878; FBgn0037901.
DR EnsemblMetazoa; FBtr0308211; FBpp0300531; FBgn0037901.
DR GeneID; 41374; -.
DR KEGG; dme:Dmel_CG6744; -.
DR UCSC; CG6744-RA; d. melanogaster.
DR CTD; 55218; -.
DR FlyBase; FBgn0037901; Exd2.
DR VEuPathDB; VectorBase:FBgn0037901; -.
DR eggNOG; KOG4373; Eukaryota.
DR GeneTree; ENSGT00390000014318; -.
DR HOGENOM; CLU_019718_0_0_1; -.
DR InParanoid; Q9VGN7; -.
DR OMA; RYYQTPK; -.
DR OrthoDB; 692844at2759; -.
DR PhylomeDB; Q9VGN7; -.
DR BioGRID-ORCS; 41374; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 41374; -.
DR PRO; PR:Q9VGN7; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037901; Expressed in embryonic/larval hemocyte (Drosophila) and 25 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008408; F:3'-5' exonuclease activity; ISS:FlyBase.
DR GO; GO:0000175; F:3'-5'-exoribonuclease 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:0070131; P:positive regulation of mitochondrial translation; IMP:FlyBase.
DR GO; GO:0016444; P:somatic cell DNA recombination; IMP: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 2: Evidence at transcript level;
KW Exonuclease; Hydrolase; Membrane; Metal-binding; Mitochondrion; Nuclease;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..583
FT /note="Exonuclease 3'-5' domain-containing protein 2"
FT /id="PRO_0000447986"
FT TOPO_DOM 1..11
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 12..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..583
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 62..228
FT /note="3'-5' exonuclease"
FT /evidence="ECO:0000255"
FT REGION 266..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..285
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 83
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT BINDING 83
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT BINDING 85
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT BINDING 213
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
SQ SEQUENCE 583 AA; 66867 MW; 562984B177952AD0 CRC64;
MTRESAVATK RNWAILAAGV GLVYVLVRHR HRLLCPLRRV WSFGSLVPQR RIEVINSVQD
PTTQWVLNEL KNHCQTFKVL GFDCEWITVG GSRRPVALLQ LSSHRGLCAL FRLCHMKQIP
QDLRELLEDD SVIKVGVAPQ EDAMKLSHDY GVGVASTLDL RFLCVMAGHK PEGLGKLSKT
HLNYTLDKHW RLACSNWEAK TLEPKQLDYA ANDALMAVAI YQKLCRDLQP KHFWQRRQLD
DNSMHNKFEP FLDVDFTKGF TLNPSGSGVT RSKGSTQSKS NKWVPKKQPY RQIATRTKDF
YDNCLLQAPD GELLCTIDRR KASWYLNQNL GTHISEEPFT VRLNFEPAGR AVGDVGRFYQ
TIKKNQCVVC GDRDAYIRKN VVPREYRKHF PLVMKSHTSD DVLLLCPTCH QLSNISDLRV
RSKLAVQCEA PFKQEDGSVK YHDDPQLKRV QSAGKALLHH GAKIPAAKKA EMEKTLLDYY
SDQTDITEDL LRQAASVEYR VENSDYCQHG ERVVQQYRDH FGGLVELERL WRQHFLHTMQ
PRFLPELWNV NHNADRLEVR ASEGRIDKAD LMVAGLDAKI KET
