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 16-OCT-2019, entry version 169. 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; OC Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; 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., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA 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., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA 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., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic 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., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., 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- RT recombination 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., RA Rojas A.M., Antolin-Fontes A., Samino-Gene S., Raught B., RA Gonzalez-Reyes A., Ribas de Pouplana L., Doherty A.J., Yanes O., RA 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 CC metabolism. {ECO:0000269|PubMed:18056975, CC 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 CC antioxidant diet. {ECO:0000269|PubMed:29335528}. CC -!- SIMILARITY: Belongs to the EXD2 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; 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 SMR; Q9VGN7; -. DR DIP; DIP-23707N; -. DR IntAct; Q9VGN7; 2. DR STRING; 7227.FBpp0081878; -. DR PRIDE; Q9VGN7; -. 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 eggNOG; KOG4373; Eukaryota. DR eggNOG; ENOG410XS63; LUCA. DR GeneTree; ENSGT00390000014318; -. DR KO; K20777; -. DR OMA; DCEWITV; -. DR OrthoDB; 692844at2759; -. DR GenomeRNAi; 41374; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0037901; Expressed in 32 organ(s), highest expression level in embryonic/larval hemocyte (Drosophila). 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: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 Complete proteome; Exonuclease; Hydrolase; Membrane; Metal-binding; KW Mitochondrion; Nuclease; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1 583 Exonuclease 3'-5' domain-containing FT protein 2. FT /FTId=PRO_0000447986. FT TOPO_DOM 1 11 Mitochondrial intermembrane. FT {ECO:0000305}. FT TRANSMEM 12 29 Helical. {ECO:0000255}. FT TOPO_DOM 30 583 Cytoplasmic. {ECO:0000305}. FT DOMAIN 62 228 3'-5' exonuclease. {ECO:0000255}. FT METAL 83 83 Divalent metal cation 1; catalytic. FT {ECO:0000250|UniProtKB:Q9NVH0}. FT METAL 83 83 Divalent metal cation 2; catalytic. FT {ECO:0000250|UniProtKB:Q9NVH0}. FT METAL 85 85 Divalent metal cation 1; catalytic. FT {ECO:0000250|UniProtKB:Q9NVH0}. FT METAL 213 213 Divalent metal cation 1; catalytic. FT {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 //