ID DCR2_DROME Reviewed; 1722 AA. AC A1ZAW0; Q95YG3; DT 28-JUN-2023, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 1. DT 02-SEP-2026, entry version 171. DE RecName: Full=Endoribonuclease Dcr-2 {ECO:0000303|PubMed:21245036}; DE Short=Protein Dicer-2 {ECO:0000303|Ref.1}; DE EC=3.1.26.3 {ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:21419681, ECO:0000269|PubMed:27872309, ECO:0000269|PubMed:28416567, ECO:0000269|PubMed:29550490, ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:34257295}; GN Name=Dcr-2 {ECO:0000303|PubMed:21245036, GN ECO:0000312|FlyBase:FBgn0034246}; GN Synonyms=dcr {ECO:0000312|EMBL:AAF57830.2}, dic2 GN {ECO:0000312|EMBL:AAF57830.2}, Dicer2 {ECO:0000312|EMBL:AAF57830.2}; GN ORFNames=CG6493 {ECO:0000312|FlyBase:FBgn0034246}; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida; OC Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota; OC Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803}; RN [1] {ECO:0000312|EMBL:BAB69959.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RA Zenno S.; RT "Cloning of Dicer-2 cDNA from Drosophila melanogaster."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000312|Proteomes:UP000000803} 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:0000312|Proteomes:UP000000803} 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:AEL30809.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley {ECO:0000312|EMBL:AEL30809.1}; RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.; RL Submitted (AUG-2011) to the EMBL/GenBank/DDBJ databases. RN [5] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, DISRUPTION PHENOTYPE, AND RP MUTAGENESIS OF GLY-31; GLY-173; GLU-1210; GLU-1237; GLU-1371 AND GLU-1617. RX PubMed=15066283; DOI=10.1016/s0092-8674(04)00261-2; RA Lee Y.S., Nakahara K., Pham J.W., Kim K., He Z., Sontheimer E.J., RA Carthew R.W.; RT "Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA RT silencing pathways."; RL Cell 117:69-81(2004). RN [6] {ECO:0000305} RP FUNCTION, COFACTOR, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-31. RX PubMed=15550672; DOI=10.1126/science.1102755; RA Tomari Y., Matranga C., Haley B., Martinez N., Zamore P.D.; RT "A protein sensor for siRNA asymmetry."; RL Science 306:1377-1380(2004). RN [7] {ECO:0000305} RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=16554838; DOI=10.1038/ni1335; RA Galiana-Arnoux D., Dostert C., Schneemann A., Hoffmann J.A., Imler J.L.; RT "Essential function in vivo for Dicer-2 in host defense against RNA viruses RT in drosophila."; RL Nat. Immunol. 7:590-597(2006). RN [8] {ECO:0000305} RP FUNCTION. RX PubMed=18953338; DOI=10.1038/ni.1664; RA Deddouche S., Matt N., Budd A., Mueller S., Kemp C., Galiana-Arnoux D., RA Dostert C., Antoniewski C., Hoffmann J.A., Imler J.L.; RT "The DExD/H-box helicase Dicer-2 mediates the induction of antiviral RT activity in drosophila."; RL Nat. Immunol. 9:1425-1432(2008). RN [9] RP FUNCTION, AND INTERACTION WITH LOQS (ISOFORM PD). RX PubMed=19635780; DOI=10.1261/rna.1611309; RA Zhou R., Czech B., Brennecke J., Sachidanandam R., Wohlschlegel J.A., RA Perrimon N., Hannon G.J.; RT "Processing of Drosophila endo-siRNAs depends on a specific Loquacious RT isoform."; RL RNA 15:1886-1895(2009). RN [10] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH R2D2, RP BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, AND MUTAGENESIS OF GLY-31. RX PubMed=21419681; DOI=10.1016/j.molcel.2011.03.002; RA Cenik E.S., Fukunaga R., Lu G., Dutcher R., Wang Y., Tanaka Hall T.M., RA Zamore P.D.; RT "Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP- RT driven ribonuclease."; RL Mol. Cell 42:172-184(2011). RN [11] {ECO:0000305} RP FUNCTION, IDENTIFICATION IN THE SIRNA-RISC LOADING COMPLEX, AND INTERACTION RP WITH R2D2 AND LOQS (ISOFORM PD). RX PubMed=21245036; DOI=10.1093/nar/gkq1324; RA Hartig J.V., Foerstemann K.; RT "Loqs-PD and R2D2 define independent pathways for RISC generation in RT Drosophila."; RL Nucleic Acids Res. 39:3836-3851(2011). RN [12] RP FUNCTION. RX PubMed=23063653; DOI=10.1016/j.cell.2012.09.027; RA Fukunaga R., Han B.W., Hung J.H., Xu J., Weng Z., Zamore P.D.; RT "Dicer partner proteins tune the length of mature miRNAs in flies and RT mammals."; RL Cell 151:533-546(2012). RN [13] {ECO:0000305} RP FUNCTION, DOMAIN, AND MUTAGENESIS OF ALA-500. RX PubMed=24009507; DOI=10.1371/journal.ppat.1003579; RA Marques J.T., Wang J.P., Wang X., de Oliveira K.P., Gao C., Aguiar E.R., RA Jafari N., Carthew R.W.; RT "Functional specialization of the small interfering RNA pathway in response RT to virus infection."; RL PLoS Pathog. 9:e1003579-e1003579(2013). RN [14] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF GLY-31. RX PubMed=24488111; DOI=10.1002/embj.201387176; RA Fukunaga R., Colpan C., Han B.W., Zamore P.D.; RT "Inorganic phosphate blocks binding of pre-miRNA to Dicer-2 via its PAZ RT domain."; RL EMBO J. 33:371-384(2014). RN [15] RP FUNCTION, AND MUTAGENESIS OF LYS-34; ASP-1217 AND ASP-1476. RX PubMed=25891075; DOI=10.1016/j.molcel.2015.03.012; RA Sinha N.K., Trettin K.D., Aruscavage P.J., Bass B.L.; RT "Drosophila dicer-2 cleavage is mediated by helicase- and dsRNA termini- RT dependent states that are modulated by Loquacious-PD."; RL Mol. Cell 58:406-417(2015). RN [16] {ECO:0000305} RP FUNCTION, IDENTIFICATION IN THE SIRNA-RISC LOADING COMPLEX, INTERACTION RP WITH R2D2 AND TAF11, AND SUBCELLULAR LOCATION. RX PubMed=26257286; DOI=10.1016/j.molcel.2015.07.006; RA Liang C., Wang Y., Murota Y., Liu X., Smith D., Siomi M.C., Liu Q.; RT "TAF11 Assembles the RISC Loading Complex to Enhance RNAi Efficiency."; RL Mol. Cell 59:807-818(2015). RN [17] {ECO:0000305} RP FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE. RX PubMed=26601278; DOI=10.1126/sciadv.1500228; RA Wang Z., Wu D., Liu Y., Xia X., Gong W., Qiu Y., Yang J., Zheng Y., Li J., RA Wang Y.F., Xiang Y., Hu Y., Zhou X.; RT "Drosophila Dicer-2 has an RNA interference-independent function that RT modulates Toll immune signaling."; RL Sci. Adv. 1:e1500228-e1500228(2015). RN [18] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF GLY-31; HIS-743; RP ARG-752; ARG-759; ARG-943; ARG-956; ASP-1217 AND ASP-1476. RX PubMed=27872309; DOI=10.1073/pnas.1612393113; RA Kandasamy S.K., Fukunaga R.; RT "Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA RT production."; RL Proc. Natl. Acad. Sci. U.S.A. 113:14031-14036(2016). RN [19] {ECO:0000305} RP FUNCTION, AND INTERACTION WITH LOQS (ISOFORM PD). RX PubMed=29040648; DOI=10.1093/nar/gkx886; RA Tants J.-N., Fesser S., Kern T., Stehle R., Geerlof A., Wunderlich C., RA Juen M., Hartlmuller C., Boettcher R., Kunzelmann S., Lange O., Kreutz C., RA Foerstemann K., Sattler M.; RT "Molecular basis for asymmetry sensing of siRNAs by the Drosophila Loqs- RT PD/Dcr-2 complex in RNA interference."; RL Nucleic Acids Res. 45:12536-12550(2017). RN [20] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH LOQS (ISOFORM PD). RX PubMed=28874570; DOI=10.1073/pnas.1707063114; RA Trettin K.D., Sinha N.K., Eckert D.M., Apple S.E., Bass B.L.; RT "Loquacious-PD facilitates Drosophila Dicer-2 cleavage through interactions RT with the helicase domain and dsRNA."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E7939-E7948(2017). RN [21] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH R2D2, TISSUE SPECIFICITY, RP DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 1653-PRO--ALA-1722. RX PubMed=28416567; DOI=10.1261/rna.059915.116; RA Kandasamy S.K., Zhu L., Fukunaga R.; RT "The C-terminal dsRNA-binding domain of Drosophila Dicer-2 is crucial for RT efficient and high-fidelity production of siRNA and loading of siRNA to RT Argonaute2."; RL RNA 23:1139-1153(2017). RN [22] {ECO:0000305} RP FUNCTION, INTERACTION WITH WISP, DEVELOPMENTAL STAGE, AND DISRUPTION RP PHENOTYPE. RX PubMed=29317541; DOI=10.1261/rna.065417.117; RA Coll O., Guitart T., Villalba A., Papin C., Simonelig M., Gebauer F.; RT "Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation."; RL RNA 24:529-539(2018). RN [23] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND COFACTOR. RX PubMed=29550490; DOI=10.1016/j.bbrc.2018.03.108; RA Fukunaga R.; RT "Loquacious-PD removes phosphate inhibition of Dicer-2 processing of RT hairpin RNAs into siRNAs."; RL Biochem. Biophys. Res. Commun. 498:1022-1027(2018). RN [24] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LOQS (ISOFORM PD), DOMAIN, RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-31; ARG-759; ARG-943 AND RP ARG-956. RX PubMed=32843367; DOI=10.1261/rna.077289.120; RA Donelick H.M., Talide L., Bellet M., Aruscavage P.J., Lauret E., RA Aguiar E.R.G.R., Marques J.T., Meignin C., Bass B.L.; RT "In vitro studies provide insight into effects of Dicer-2 helicase RT mutations in Drosophila melanogaster."; RL RNA 26:1847-1861(2020). RN [25] {ECO:0000305} RP FUNCTION, AND MUTAGENESIS OF GLY-31. RX PubMed=34590626; DOI=10.1039/d1cc03843e; RA Jonely M., Singh R.K., Donelick H.M., Bass B.L., Noriega R.; RT "Loquacious-PD regulates the terminus-dependent molecular recognition of RT Dicer-2 toward double-stranded RNA."; RL Chem. Commun. (Camb.) 57:10879-10882(2021). RN [26] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLY-31. RX PubMed=34257295; DOI=10.1038/s41467-021-24555-1; RA Naganuma M., Tadakuma H., Tomari Y.; RT "Single-molecule analysis of processive double-stranded RNA cleavage by RT Drosophila Dicer-2."; RL Nat. Commun. 12:4268-4268(2021). RN [27] {ECO:0007744|PDB:6BU9, ECO:0007744|PDB:6BUA} RP STRUCTURE BY ELECTRON MICROSCOPY (6.80 ANGSTROMS), FUNCTION, CATALYTIC RP ACTIVITY, COFACTOR, DOMAIN, AND MUTAGENESIS OF LYS-34; PHE-225; HIS-743; RP ARG-752; ARG-759; ARG-943; ARG-956; ASP-1217 AND ASP-1476. RX PubMed=29269422; DOI=10.1126/science.aaq0921; RA Sinha N.K., Iwasa J., Shen P.S., Bass B.L.; RT "Dicer uses distinct modules for recognizing dsRNA termini."; RL Science 359:329-334(2018). RN [28] {ECO:0007744|PDB:7V6B, ECO:0007744|PDB:7V6C} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS), FUNCTION, IDENTIFICATION RP IN THE SIRNA-RISC LOADING COMPLEX, INTERACTION WITH R2D2, DOMAIN, AND RP MUTAGENESIS OF ARG-324; GLU-331 AND ARG-759. RX PubMed=35768503; DOI=10.1038/s41586-022-04790-2; RA Yamaguchi S., Naganuma M., Nishizawa T., Kusakizako T., Tomari Y., RA Nishimasu H., Nureki O.; RT "Structure of the Dicer-2-R2D2 heterodimer bound to a small RNA duplex."; RL Nature 607:393-398(2022). RN [29] {ECO:0007744|PDB:7W0A, ECO:0007744|PDB:7W0B, ECO:0007744|PDB:7W0C, ECO:0007744|PDB:7W0D, ECO:0007744|PDB:7W0E, ECO:0007744|PDB:7W0F} RP STRUCTURE BY ELECTRON MICROSCOPY (3.12 ANGSTROMS), FUNCTION, CATALYTIC RP ACTIVITY, INTERACTION WITH LOQS (ISOFORM PD), COFACTOR, DOMAIN, AND RP MUTAGENESIS OF ARG-1330. RX PubMed=35768513; DOI=10.1038/s41586-022-04911-x; RA Su S., Wang J., Deng T., Yuan X., He J., Liu N., Li X., Huang Y., RA Wang H.W., Ma J.; RT "Structural insights into dsRNA processing by Drosophila Dicer-2-Loqs-PD."; RL Nature 607:399-406(2022). CC -!- FUNCTION: Double-stranded RNA (dsRNA) endoribonuclease which cleaves CC endogenous (endo), exogenous (exo), and viral dsRNAs to produce short CC interfering RNAs (siRNAs) (PubMed:15066283, PubMed:16554838, CC PubMed:18953338, PubMed:19635780, PubMed:21419681, PubMed:23063653, CC PubMed:24009507, PubMed:24488111, PubMed:25891075, PubMed:27872309, CC PubMed:28416567, PubMed:28874570, PubMed:29040648, PubMed:29317541, CC PubMed:29550490, PubMed:32843367, PubMed:34257295, PubMed:34590626, CC PubMed:35768513). The generated siRNAs then mediate gene silencing, CC also called RNA interference (RNAi), by controlling the elimination of CC endogenous transcripts from mobile and repetitive DNA elements of the CC genome as well as exogenous RNA of viral origin (PubMed:15066283, CC PubMed:16554838, PubMed:18953338, PubMed:21419681, PubMed:23063653, CC PubMed:24009507, PubMed:24488111, PubMed:27872309, PubMed:28416567, CC PubMed:28874570, PubMed:29040648, PubMed:29317541, PubMed:29550490, CC PubMed:32843367, PubMed:34257295, PubMed:34590626, PubMed:35768513). CC Also acts in an RNAi-independent manner to activate translation through CC cytoplasmic polyadenylation (PubMed:29317541). As well as its role in CC dsRNA processing, essential in several steps of the siRNA biogenesis CC pathway, including siRNA loading into the Argonaute 2 (AGO2)-containing CC RNA-induced silencing complex (siRISC), length-dependent dicing and CC guide strand selection for target silencing by the siRISC CC (PubMed:15066283, PubMed:15550672, PubMed:21245036, PubMed:21419681, CC PubMed:26257286, PubMed:27872309, PubMed:28416567, PubMed:34590626, CC PubMed:35768503). Cleaves dsRNAs into siRNAs that are predominantly CC around twenty-one nucleotides in length (PubMed:15066283, CC PubMed:21419681, PubMed:23063653, PubMed:24488111, PubMed:27872309, CC PubMed:28416567, PubMed:28874570, PubMed:29269422, PubMed:29550490, CC PubMed:32843367, PubMed:34257295, PubMed:35768513). Displays a CC preference for binding and processing blunt termini (BLT), likely non- CC self dsRNAs, over dsRNAs with 2 nucleotides 3' overhanging (3'ovr) CC termini, which are typically the structure of endogenous dsRNAs CC (PubMed:25891075, PubMed:29269422, PubMed:29550490, PubMed:32843367, CC PubMed:34257295, PubMed:34590626). According to many reports, the CC cleavage reaction mode of the enzyme changes according to the termini CC of the dsRNA substrate (PubMed:21419681, PubMed:25891075, CC PubMed:28416567, PubMed:29269422, PubMed:32843367, PubMed:34590626). CC BLT dsRNAs undergo an ATP-dependent processive reaction whereby CC multiple siRNAs of heterogeneous sizes are produced before the enzyme CC dissociates (PubMed:21419681, PubMed:25891075, PubMed:28416567, CC PubMed:29269422, PubMed:29550490, PubMed:32843367, PubMed:34590626). In CC contrast, dsRNAs with 3'ovr termini, which are typically the structure CC of endogenous dsRNAs, undergo ATP-independent, distributive cleavage CC whereby the enzyme dissociates after each cleavage to produce siRNAs of CC around 22 nucleotides (PubMed:25891075, PubMed:29269422, CC PubMed:32843367, PubMed:34590626). However, according to another CC report, the mode of cleavage reaction is not affected by the terminal CC structures of the dsRNAs substrates (PubMed:34257295). This report CC suggests that the enzyme is able to initiate processive cleavage of CC both BLT and 3'ovr dsRNA substrates, and only rarely initiates CC distributive cleavage (PubMed:34257295). During dsRNA processing and CC AGO2-loading, requires association with dsRNA-binding accessory CC proteins loqs isoform PD (loqs-PD) and r2d2 (PubMed:15550672, CC PubMed:21245036, PubMed:24009507, PubMed:28416567, PubMed:28874570, CC PubMed:29040648, PubMed:29550490). Functions with r2d2 to form the CC siRNA-mediated RISC loading complex (siRLC) which is responsible for CC Ago2-loading of endo- and exo-siRNAs (PubMed:15550672, PubMed:21245036, CC PubMed:28416567, PubMed:35768503). Interaction with loqs-PD increases CC initial binding to dsRNA substrates and promotes processing of a subset CC of endo- and exo-dsRNAs (PubMed:21245036, PubMed:24009507, CC PubMed:28874570, PubMed:29040648, PubMed:29550490, PubMed:34257295). In CC the absence of r2d2, may also form an alternative siRLC with loqs-PD to CC load siRNAs into the siRISC (PubMed:21245036). Function with loqs-PD CC allows the dicer enzyme to cleave endogenous dsRNA templates CC independently of their termini, and is required for ATP-dependent CC processing of a subset of siRNAs but is not required for antiviral RNAi CC (PubMed:24009507, PubMed:25891075, PubMed:29269422, PubMed:29550490, CC PubMed:32843367, PubMed:34590626). This suggests that the enzyme's CC intrinsic termini preferences function in viral defense, while function CC with loqs-PD allows processing of endogenous dsRNAs with diverse CC termini (PubMed:29269422, PubMed:32843367). However, according to CC another report the mode of cleavage reaction is not affected by the CC presence or absence of loqs-PD (PubMed:34257295). Loaded siRNAs serve CC as a guide to direct the siRISC to complementary RNAs to degrade them CC or prevent their translation (PubMed:15066283). The siRLC plays an CC important role in the ATP-dependent asymmetry sensing of the duplex, CC and is therefore also responsible for the selection of the strand that CC ultimately acts as the guide siRNA for the siRISC (PubMed:29040648, CC PubMed:35768503). Thermodynamically asymmetric siRNAs are preoriented CC in the siRLC by either the dsRNA-binding r2d2 protein, or the loqs-PD CC protein in the alternative siRLC, which preferentially bind to the most CC thermodynamically stable strand prior to loading onto AGO2 CC (PubMed:15550672, PubMed:29040648, PubMed:35768503). Both r2d2 and Dcr- CC 2 also initiate unwinding of the siRNA duplex, at which point the CC heterodimer is exchanged by AGO2 (PubMed:15550672). The strand that was CC bound by r2d2 is discarded while the one that was bound by Dcr-2 is CC loaded onto Ago2 and serves as guide to direct the siRISC to CC complementary RNAs to degrade them or prevent their translation CC (PubMed:15550672). Independently of its role in RNAi, acts with the CC cytoplasmic poly(A) polymerase wisp to promote cytoplasmic CC polyadenylation and translational activation of certain messenger RNAs CC including r2d2 and toll (Tl) transcripts (PubMed:26601278, CC PubMed:29317541). Consequently it is involved in the post- CC transcriptional regulation of the Toll immune signaling pathway and CC promoting resistance to fungal and viral infections (PubMed:26601278, CC PubMed:29317541). As an RNA-binding protein, likely functions in CC cytoplasmic polyadenylation by recruiting the poly(A) RNA polymerase CC wisp to target mRNAs (PubMed:26601278, PubMed:29317541). CC {ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:15550672, CC ECO:0000269|PubMed:16554838, ECO:0000269|PubMed:18953338, CC ECO:0000269|PubMed:19635780, ECO:0000269|PubMed:21245036, CC ECO:0000269|PubMed:21419681, ECO:0000269|PubMed:23063653, CC ECO:0000269|PubMed:24009507, ECO:0000269|PubMed:24488111, CC ECO:0000269|PubMed:25891075, ECO:0000269|PubMed:26257286, CC ECO:0000269|PubMed:26601278, ECO:0000269|PubMed:27872309, CC ECO:0000269|PubMed:28416567, ECO:0000269|PubMed:28874570, CC ECO:0000269|PubMed:29040648, ECO:0000269|PubMed:29269422, CC ECO:0000269|PubMed:29317541, ECO:0000269|PubMed:29550490, CC ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:34257295, CC ECO:0000269|PubMed:34590626, ECO:0000269|PubMed:35768503, CC ECO:0000269|PubMed:35768513}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3; CC Evidence={ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:21419681, CC ECO:0000269|PubMed:24488111, ECO:0000269|PubMed:27872309, CC ECO:0000269|PubMed:28416567, ECO:0000269|PubMed:28874570, CC ECO:0000269|PubMed:29269422, ECO:0000269|PubMed:29550490, CC ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:34257295}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:35768513}; CC -!- COFACTOR: CC Name=ATP; Xref=ChEBI:CHEBI:30616; CC Evidence={ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:15550672, CC ECO:0000269|PubMed:24488111, ECO:0000269|PubMed:29269422, CC ECO:0000269|PubMed:29550490, ECO:0000269|PubMed:35768513}; CC -!- ACTIVITY REGULATION: Activity towards dsRNAs such as hairpin dsRNAs, CC short dsRNAs and microRNAs, is inhibited by inorganic phosphate CC (PubMed:21419681, PubMed:24488111, PubMed:29550490). Binding to CC inorganic phosphate may function in substrate discrimination by CC blocking the enzyme from binding to nonphysiological substrates, as the CC presence of inorganic phosphate at physiological concentrations CC inhibits processing of the inappropriate substrates microRNAs (pre- CC miRNAs) and short dsRNAs but does not affect cleavage of long dsRNAs CC (PubMed:21419681, PubMed:24488111, PubMed:29550490). In the presence of CC inorganic phosphate, interaction with loqs (isoform PD) enables the CC enzyme to process blunt-end hairpin RNA substrates and produce endo- CC siRNAs, likely by increasing binding affinity of the enzyme to the CC hairpin dsRNAs (PubMed:29550490). {ECO:0000269|PubMed:21419681, CC ECO:0000269|PubMed:24488111, ECO:0000269|PubMed:29550490}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6 nM for 515 bp dsRNA {ECO:0000269|PubMed:21419681}; CC KM=2 nM for 515 bp dsRNA (in the presence of r2d2) CC {ECO:0000269|PubMed:21419681}; CC KM=0.4 nM for 515 bp dsRNA (in the presence of loqs isoform PD) CC {ECO:0000269|PubMed:21419681}; CC KM=14000 nM for ATP (in the presence of 515 bp dsRNA) CC {ECO:0000269|PubMed:21419681}; CC Note=kcat is 0.03 min(-1) for dsRNA consumption (PubMed:21419681). CC kcat is 0.03 min(-1) for dsRNA consumption (in the presence of r2d2) CC (PubMed:21419681). kcat is 0.03 min(-1) for dsRNA consumption (in the CC presence of loqs isoform PD) (PubMed:21419681). kcat is 4 min(-1) for CC siRNA production (PubMed:21419681). kcat is 93 min(-1) for ATP CC hydrolysis in the presence of dsRNA (PubMed:21419681). CC {ECO:0000269|PubMed:21419681}; CC -!- SUBUNIT: Component of the siRNA-directed RISC loading complex (siRLC), CC composed of at least Dcr-2, r2d2 and Taf11, which processes dsRNAs into CC duplex siRNAs which they then load onto AGO2 to initiate formation of CC the RNA-induced silencing complex (siRISC) (PubMed:21245036, CC PubMed:26257286, PubMed:35768503). The Dcr-2-r2d2 complex exists as a CC heterodimer and heterotetramer, with the latter showing higher siRNA CC binding activity (PubMed:26257286). Interacts (via N-terminus) with the CC siRISC loading cofactor r2d2; interaction is essential for formation of CC the siRLC and consequently, formation of the siRISC (PubMed:21245036, CC PubMed:21419681, PubMed:28416567, PubMed:35768503). Interacts with CC Taf11 (PubMed:26257286). Taf11 appears to form a tetramer which CC facilitates or stabilizes formation of the Dcr-2-r2d2 heterotetramer CC (PubMed:26257286). Interacts (via N-terminus) with dicing cofactor loqs CC isoform PD (loqs-PD) (via C-terminus); interaction is required for RNAi CC activity in producing siRNAs from a subset of endo- and exo-dsRNAs CC (PubMed:19635780, PubMed:21245036, PubMed:28874570, PubMed:29040648, CC PubMed:32843367, PubMed:35768513). In the absence of r2d2, may also be CC able to form an alternative siRLC with loqs-PD (PubMed:21245036). CC Interacts with wisp (via C-terminus) (PubMed:29317541). Able to CC interact with the other loqs isoforms (isoforms PA, PB and PC) CC (PubMed:19635780). {ECO:0000269|PubMed:19635780, CC ECO:0000269|PubMed:21245036, ECO:0000269|PubMed:21419681, CC ECO:0000269|PubMed:26257286, ECO:0000269|PubMed:28416567, CC ECO:0000269|PubMed:28874570, ECO:0000269|PubMed:29040648, CC ECO:0000269|PubMed:29317541, ECO:0000269|PubMed:32843367, CC ECO:0000269|PubMed:35768503, ECO:0000269|PubMed:35768513}. CC -!- INTERACTION: CC A1ZAW0; Q9VLW8: r2d2; NbExp=3; IntAct=EBI-84244, EBI-156415; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26257286}. Cytoplasm CC {ECO:0000269|PubMed:26257286}. Cytoplasm, Cytoplasmic ribonucleoprotein CC granule {ECO:0000269|PubMed:26257286}. CC -!- TISSUE SPECIFICITY: In ovary (at protein level). CC {ECO:0000269|PubMed:28416567}. CC -!- DEVELOPMENTAL STAGE: In embryos (at protein level). CC {ECO:0000269|PubMed:29317541}. CC -!- DOMAIN: When in complex with loqs isoform PD (loqs-PD), undergoes CC significant conformational changes during the full ATP-dependent dicing CC reaction cycle for processing a 50 bp dsRNA with a 3' two-nucleotide CC overhang and a 5' monophosphate terminus (PubMed:35768513). At the CC initial dsRNA binding stage, the helicase and DUF283 domains transition CC from an extended to a closed conformation, this anchors the bound dsRNA CC through major and minor groove recognition and forms the ATP- and 5'- CC phosphate binding pockets required for dicing activity CC (PubMed:35768513). In the next ATP hydrolysis-driven steps, the dsRNAs CC is thread through the helicase domain towards the catalytic center CC (PubMed:35768513). The overall domain configuration is relatively rigid CC during the translocation process until the dsRNA terminus reaches the CC Platform-PAZ domains (PubMed:35768513). During the early-translocation CC stage, in which about 8 bp of the dsRNA duplex is threaded through the CC helicase domain towards the catalytic center, interactions between the CC DUF283 and RIIIDb domains prevent non-specific cleavage by blocking the CC access of dsRNA to the RNase active center (PubMed:35768513). In the CC mid-translocation stage, in which about 17 bp of the dsRNA duplex is CC thread towards the catalytic center, the dsRBD domain binds to the CC dsRNA, in the process bending and pushing the dsRNA towards the PAZ CC domain (PubMed:35768513). At the end of the translocation stage, around CC 21 bp of the dsRNA threads through the helicase domain into the PAZ- CC platform cassette, in the process disrupting the DUF283-RNaseIIIb CC interaction, allowing the dsRNA substrate to enter the catalytic active CC center of the RIIID domains for precise cleavage, and thus achieves the CC fully active dicing conformation (PubMed:35768513). In this structure, CC a clear breakage of the dsRNA after the dicing near to the catalytic CC center occurs exactly 21 bp away from the PAZ-domain-binding terminus CC (PubMed:35768513). During the post-dicing state, the cleaved siRNA is CC released, and the remaining dsRNA duplex bound by the helicase domain CC returns to a conformation similar to the early-translocation state, CC which enables the complex to start the next dicing cycle CC (PubMed:35768513). {ECO:0000269|PubMed:35768513}. CC -!- DOMAIN: The N-terminal helicase domain, containing the Helicase ATP- CC binding, Helicase C-terminal and Helicase insertion domains, functions CC in dsRNA stimulated ATPase activity and RNA translocation during the CC dicing reaction (PubMed:15066283, PubMed:21419681, PubMed:35768503, CC PubMed:35768513). Essential for processing endogenous and viral dsRNAs CC (PubMed:24009507, PubMed:28416567, PubMed:32843367). Binds and CC hydrolyzes ATP enabling the dicer to translocate along the long dsRNA CC substrates, and produce siRNAs processively from the end CC (PubMed:21419681, PubMed:29269422). Some reports suggest the domain is CC essential for the recognition and initial binding of both blunt (BLT) CC and 3' overhanging (3'ovr) termini dsRNA substrates (PubMed:35768503, CC PubMed:35768513). However, another reports found that the helicase CC domain is only required for binding and correct cleavage of BLT dsRNAs CC and is dispensable for processing of 3'ovr termini dsRNAs CC (PubMed:29269422, PubMed:32843367). One of the reports suggest that the CC helicase domain recognizes dsRNA with BLT termini, and then initiates CC processive cleavage via a threading mechanism in which the BLT dsRNA is CC locally unwound and threaded through the helicase domain in an ATP- CC dependent manner (PubMed:29269422). {ECO:0000269|PubMed:15066283, CC ECO:0000269|PubMed:21419681, ECO:0000269|PubMed:24009507, CC ECO:0000269|PubMed:28416567, ECO:0000269|PubMed:29269422, CC ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:35768503, CC ECO:0000269|PubMed:35768513}. CC -!- DOMAIN: The PAZ and platform domain is important for ensuring length CC fidelity of siRNAs, substrate discrimination, cleavage and anchoring of CC 3' overhanging (3'ovr) termini substrates, and the positive regulation CC of Tl (PubMed:26601278, PubMed:27872309, PubMed:29269422, CC PubMed:35768503). The platform-PAZ domains are important for mediating CC the ATP-independent cleavage of dsRNAs with 3' overhanging (3'ovr) CC dsRNAs into 22mer siRNAs (PubMed:29269422). Substrate dsRNAs with blunt CC termini, are threaded through the helicase domain, cleaved and then the CC 2-nt 3' overhang of the dsRNA is recognized and anchored by the 5'- CC pocket in the platform-PAZ domain (PubMed:29269422). The PAZ domain CC recognizes and anchors the 5'-monophosphate of long dsRNA substrates, CC positioning the substrate so that the RNase III domain can cleave the CC dsRNAs 21 nt away from their 5' end (PubMed:27872309, PubMed:35768503). CC Although it is important for ensuring length fidelity of 21-nt siRNA CC production, it is not required for efficient siRNA production CC (PubMed:27872309, PubMed:35768503). Important for substrate CC discrimination (PubMed:24488111, PubMed:29550490). Inorganic phosphate CC appears to occupy the same binding pocket in the PAZ domain as the 5' CC monophosphorylated end of short dsRNAs, pre-miRNAs or hairpin RNA CC substrates, and so once bound, the inorganic phosphate likely blocks CC binding and thus cleavage of the dsRNAs (PubMed:24488111, CC PubMed:29550490). Physiological concentrations of inorganic phosphate CC inhibit processing of the inappropriate substrates microRNAs (pre- CC miRNAs) and short dsRNAs, whereas cleavage of long dsRNAs is not CC inhibited possibly because they are recognized by a different domain/s CC i.e. the helicase domain and/or the central dsRNA binding domain CC (PubMed:21419681, PubMed:24488111, PubMed:29550490). This suggests that CC binding to inorganic phosphate may block binding to nonphysiological CC substrates, such as pre-miRNAs function to prevent the enzyme from CC processing nonphysiological dsRNAs substrates (PubMed:21419681, CC PubMed:24488111, PubMed:29550490). This domain is also important for CC the ATP-dependent cleavage reaction (PubMed:32843367). The PAZ domain CC also interacts with the Tl mRNA 3'UTR, and is therefore important for CC the positive regulation of Tl at the post-transcriptional level, and CC thus mediating Toll signaling (PubMed:26601278). CC {ECO:0000269|PubMed:21419681, ECO:0000269|PubMed:24488111, CC ECO:0000269|PubMed:26601278, ECO:0000269|PubMed:27872309, CC ECO:0000269|PubMed:29269422, ECO:0000269|PubMed:29550490, CC ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:35768503}. CC -!- DOMAIN: The DRBM domain or RNA binding domain (RBD), is important for CC efficient and high-fidelity production of 21 nucleotide siRNAs, and CC siRNA loading onto AGO2. {ECO:0000269|PubMed:28416567}. CC -!- DOMAIN: Interactions between the DUF283 and RIIIDb domains prevent non- CC specific cleavage by blocking the access of dsRNA to the RNase active CC center. {ECO:0000269|PubMed:35768513}. CC -!- DISRUPTION PHENOTYPE: Abolishes RNA-induced silencing complex (RISC) CC assembly and RNAi silencing activity (PubMed:15066283, PubMed:28416567, CC PubMed:29317541, PubMed:32843367). Abolishes siRNA unwinding prior to CC loading onto the RNA-induced silencing complex (RISC) CC (PubMed:15550672). Decreased levels of endo-siRNAs (PubMed:15066283, CC PubMed:16554838, PubMed:24488111, PubMed:28416567, PubMed:29317541, CC PubMed:32843367). Increased susceptibility to infection with RNA CC viruses such as Flock House virus, Drosophila C virus or Sindbis virus CC (PubMed:16554838). No effect on the processing of pre-miRNAs CC (PubMed:24488111). RNAi-mediated knockdown inhibits the induction of CC the antifungal peptide Drs in response to M.luteus challenge CC (PubMed:26601278). Also highly susceptible to infection with CC A.fumigatus, with 80% of flies dying six days after infection CC (PubMed:26601278). {ECO:0000269|PubMed:15066283, CC ECO:0000269|PubMed:15550672, ECO:0000269|PubMed:16554838, CC ECO:0000269|PubMed:24488111, ECO:0000269|PubMed:26601278, CC ECO:0000269|PubMed:28416567, ECO:0000269|PubMed:29317541, CC ECO:0000269|PubMed:32843367}. CC -!- SIMILARITY: Belongs to the helicase family. Dicer subfamily. CC {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; AE013599; AAF57830.2; -; Genomic_DNA. DR EMBL; AB073024; BAB69959.1; -; mRNA. DR EMBL; BT128787; AEL30809.1; -; mRNA. DR RefSeq; NP_523778.2; NM_079054.5. DR PDB; 6BU9; EM; 6.80 A; A=1-1722. DR PDB; 6BUA; EM; 7.10 A; A=1-1722. DR PDB; 7V6B; EM; 3.30 A; A=1-1722. DR PDB; 7V6C; EM; 3.30 A; A=1-1722. DR PDB; 7W0A; EM; 3.12 A; A/E=1-1722. DR PDB; 7W0B; EM; 3.33 A; A=1-1722. DR PDB; 7W0C; EM; 3.93 A; A=1-1722. DR PDB; 7W0D; EM; 4.18 A; A/F=1-1722. DR PDB; 7W0E; EM; 4.03 A; A=1-1722. DR PDB; 7W0F; EM; 4.55 A; A=1-1722. DR PDB; 8HF0; EM; 3.72 A; A/D=1-1722. DR PDB; 8HF1; EM; 3.70 A; A/D/G=2-1722. DR PDB; 8YIG; EM; 3.15 A; A/E=2-1722. DR PDB; 8YIH; EM; 4.08 A; A=2-1722. DR PDB; 8YII; EM; 3.42 A; A=2-1722. DR AlphaFoldDB; A1ZAW0; -. DR EMDB; EMD-31741; -. DR EMDB; EMD-31742; -. DR EMDB; EMD-32236; -. DR EMDB; EMD-32237; -. DR EMDB; EMD-32238; -. DR EMDB; EMD-32239; -. DR EMDB; EMD-32240; -. DR EMDB; EMD-32241; -. DR EMDB; EMD-34707; -. DR EMDB; EMD-34708; -. DR EMDB; EMD-39318; -. DR EMDB; EMD-39319; -. DR EMDB; EMD-39320; -. DR EMDB; EMD-39321; -. DR EMDB; EMD-7290; -. DR EMDB; EMD-7291; -. DR SMR; A1ZAW0; -. DR ComplexPortal; CPX-2730; siRNA RISC-loading complex, R2D2 variant. DR ComplexPortal; CPX-2732; siRNA RISC-loading complex, loqs variant. DR DIP; DIP-54444N; -. DR FunCoup; A1ZAW0; 134. DR IntAct; A1ZAW0; 17. DR STRING; 7227.FBpp0086061; -. DR GlyGen; A1ZAW0; 1 site. DR PaxDb; 7227-FBpp0086061; -. DR PeptideAtlas; A1ZAW0; -. DR EnsemblMetazoa; FBtr0086904; FBpp0086061; FBgn0034246. DR GeneID; 36993; -. DR KEGG; dme:Dmel_CG6493; -. DR UCSC; CG6493-RA; d. melanogaster. DR AGR; FB:FBgn0034246; -. DR CTD; 36993; -. DR FlyBase; FBgn0034246; Dcr-2. DR VEuPathDB; VectorBase:FBgn0034246; -. DR eggNOG; KOG0701; Eukaryota. DR InParanoid; A1ZAW0; -. DR OMA; YHVNRMC; -. DR OrthoDB; 416741at2759; -. DR BioGRID-ORCS; 36993; 1 hit in 1 CRISPR screen. DR GenomeRNAi; 36993; -. DR PRO; PR:A1ZAW0; -. DR Proteomes; UP000000803; Chromosome 2R. DR Bgee; FBgn0034246; Expressed in adult midgut enterocyte in digestive tract and 131 other cell types or tissues. DR ExpressionAtlas; A1ZAW0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:FlyBase. DR GO; GO:0016442; C:RISC complex; IDA:FlyBase. DR GO; GO:0070578; C:RISC-loading complex; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:FlyBase. DR GO; GO:0008186; F:ATP-dependent activity, acting on RNA; IDA:FlyBase. DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central. DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:FlyBase. DR GO; GO:0004525; F:ribonuclease III activity; IDA:FlyBase. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0035197; F:siRNA binding; IDA:UniProtKB. DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central. DR GO; GO:0098586; P:cellular response to virus; IMP:FlyBase. DR GO; GO:0051607; P:defense response to virus; IMP:FlyBase. DR GO; GO:0009597; P:detection of virus; IMP:FlyBase. DR GO; GO:0009047; P:dosage compensation by hyperactivation of X chromosome; IGI:FlyBase. DR GO; GO:0098795; P:global gene silencing by mRNA cleavage; IMP:FlyBase. DR GO; GO:0031507; P:heterochromatin formation; IMP:FlyBase. DR GO; GO:0110064; P:lncRNA catabolic process; IMP:FlyBase. DR GO; GO:0007626; P:locomotory behavior; IMP:FlyBase. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:FlyBase. DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:FlyBase. DR GO; GO:0045752; P:positive regulation of Toll signaling pathway; IMP:FlyBase. DR GO; GO:0035194; P:regulatory ncRNA-mediated post-transcriptional gene silencing; IDA:FlyBase. DR GO; GO:0070922; P:RISC complex assembly; IDA:FlyBase. DR GO; GO:0009616; P:RNAi-mediated antiviral immune response; IMP:FlyBase. DR GO; GO:0030422; P:siRNA processing; IDA:UniProtKB. DR CDD; cd18034; DEXHc_dicer; 1. DR CDD; cd15903; Dicer_PBD; 1. DR CDD; cd00593; RIBOc; 2. DR CDD; cd18802; SF2_C_dicer; 1. DR FunFam; 3.30.160.20:FF:000089; Dicer-2; 1. DR FunFam; 3.40.50.300:FF:000628; Endoribonuclease Dicer; 1. DR Gene3D; 3.30.160.20; -; 1. DR Gene3D; 3.30.160.380; Dicer dimerisation domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 2.170.260.10; paz domain; 1. DR Gene3D; 1.10.1520.10; Ribonuclease III domain; 2. DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom. DR InterPro; IPR038248; Dicer_dimer_sf. DR InterPro; IPR005034; Dicer_dimerisation. DR InterPro; IPR048513; Dicer_PBD. DR InterPro; IPR048512; Dicer_platform. DR InterPro; IPR014720; dsRBD_dom. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR003100; PAZ_dom. DR InterPro; IPR000999; RNase_III_dom. DR InterPro; IPR036389; RNase_III_sf. DR PANTHER; PTHR14950; DICER-RELATED; 1. DR PANTHER; PTHR14950:SF36; ENDORIBONUCLEASE DCR-2; 1. DR Pfam; PF00270; DEAD; 1. DR Pfam; PF03368; Dicer_dimer; 1. DR Pfam; PF20931; Dicer_platform; 1. DR Pfam; PF00035; dsrm; 1. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF00636; Ribonuclease_3; 2. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SMART; SM00949; PAZ; 1. DR SMART; SM00535; RIBOc; 2. DR SUPFAM; SSF54768; dsRNA-binding domain-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF69065; RNase III domain-like; 2. DR PROSITE; PS51327; DICER_DSRBF; 1. DR PROSITE; PS50137; DS_RBD; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS50142; RNASE_3_2; 2. DR PDBsum; 6BU9; -. DR PDBsum; 6BUA; -. DR PDBsum; 7V6B; -. DR PDBsum; 7V6C; -. DR PDBsum; 7W0A; -. DR PDBsum; 7W0B; -. DR PDBsum; 7W0C; -. DR PDBsum; 7W0D; -. DR PDBsum; 7W0E; -. DR PDBsum; 7W0F; -. DR PDBsum; 8HF0; -. DR PDBsum; 8HF1; -. DR PDBsum; 8YIG; -. DR PDBsum; 8YIH; -. DR PDBsum; 8YII; -. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cytoplasm; Helicase; Hydrolase; Nuclease; KW Nucleotide-binding; Nucleus; Reference proteome; RNA-binding; KW RNA-mediated gene silencing. FT CHAIN 1..1722 FT /note="Endoribonuclease Dcr-2" FT /id="PRO_0000458153" FT DOMAIN 15..193 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 366..536 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT DOMAIN 571..673 FT /note="Dicer dsRNA-binding fold" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00657" FT DOMAIN 875..929 FT /note="PAZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142" FT DOMAIN 1177..1382 FT /note="RNase III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177" FT DOMAIN 1433..1628 FT /note="RNase III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177" FT DOMAIN 1697..1719 FT /note="DRBM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266" FT REGION 1..555 FT /note="Essential for binding and cleaving blunt termini FT (BLT) dsRNA substrates. No effect on binding or cleaving 3' FT overhanging (3'ovr) termini substrates" FT /evidence="ECO:0000269|PubMed:29269422" FT REGION 1..540 FT /note="Helicase domain; essential for RNAi silencing FT activity and binding to r2d2" FT /evidence="ECO:0000269|PubMed:28416567" FT REGION 230..347 FT /note="Helicase insertion domain; involved in FT homodimerization" FT /evidence="ECO:0000269|PubMed:35768513" FT REGION 497..509 FT /note="Sufficient for interaction with loqs isoform PD FT (loqs-PD)" FT /evidence="ECO:0000269|PubMed:28874570" FT REGION 713..855 FT /note="Platform domain" FT /evidence="ECO:0000269|PubMed:35768513" FT REGION 1268..1362 FT /note="RNase III insertion domain a; involved in FT homodimerization" FT /evidence="ECO:0000269|PubMed:35768513" FT REGION 1520..1609 FT /note="RNase III insertion domain b" FT /evidence="ECO:0000269|PubMed:35768513" FT REGION 1653..1722 FT /note="Essential for efficient and high-fidelity siRNA FT production and siRNA loading" FT /evidence="ECO:0000269|PubMed:28416567" FT MOTIF 139..142 FT /note="DEAH box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT BINDING 28..35 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MUTAGEN 31 FT /note="G->R: Disrupts ATP binding and thus ATP hydrolysis. FT Also effects binding to dsRNA substrates and siRNA FT unwinding by the RISC-loading complex is decreased. FT Severely reduced RNAi activity due to decreased generation FT of siRNAs from endogenous and viral dsRNAs. Abolishes FT ATP-dependent cleavage of blunt termini (BLT) dsRNAs but FT has no effect on ATP-independent cleavage of 3' overhanging FT (3'ovr) termini dsRNAs. Decreased binding affinities for FT BLT and 3'ovr dsRNAs. Also reduces binding to loqs. Fails FT to rescue loss of RNA silencing activity in mutants." FT /evidence="ECO:0000269|PubMed:15066283, FT ECO:0000269|PubMed:15550672, ECO:0000269|PubMed:21419681, FT ECO:0000269|PubMed:24488111, ECO:0000269|PubMed:27872309, FT ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:34257295, FT ECO:0000269|PubMed:34590626" FT MUTAGEN 34 FT /note="K->A: ATPase-defective. Unable to unwind blunt FT termini (BLT) dsRNAs but is able to bind BLT dsRNAs. No FT effect on binding to 3' overhanging (3'ovr) termini but FT abolishes binding to BLT dsRNAs; when associated with FT A-1217 and A-1476." FT /evidence="ECO:0000269|PubMed:25891075, FT ECO:0000269|PubMed:29269422" FT MUTAGEN 173 FT /note="G->E: Decreased production of siRNAs from dsRNA FT precursors." FT /evidence="ECO:0000269|PubMed:15066283" FT MUTAGEN 225 FT /note="F->G: Reduced RNAi activity due to decreased FT generation of siRNAs from endogenous and viral dsRNAs. In FT vitro, abolishes ATP-dependent cleavage of blunt termini FT (BLT) dsRNAs but has no effect on ATP-independent cleavage FT of 3' overhanging (3'ovr) termini dsRNAs. Decreased binding FT affinities for BLT and 3'ovr dsRNAs. Binding affinity for FT BLT dsRNAs is further decreased by addition of ATP. Also FT displays severely reduced binding to loqs (isoform PD). No FT effect on ATP hydrolysis. Abolishes binding to BLT and FT 3'ovr dsRNAs; when associated with A-493 and A-596." FT /evidence="ECO:0000269|PubMed:29269422, FT ECO:0000269|PubMed:32843367" FT MUTAGEN 324 FT /note="R->E: Decreased binding to r2d2." FT /evidence="ECO:0000269|PubMed:35768503" FT MUTAGEN 331 FT /note="E->R: Decreased binding to r2d2." FT /evidence="ECO:0000269|PubMed:35768503" FT MUTAGEN 500 FT /note="A->V: Increased viral replication of the Sindbis FT virus (SINV)." FT /evidence="ECO:0000269|PubMed:24009507" FT MUTAGEN 743 FT /note="H->A: Partially rescues RNA silencing activity in FT mutants. Abolishes cleavage of 3' overhanging (3'ovr) FT termini dsRNAs but has no effect on cleavage of blunt FT termini (BLT) dsRNAs, when associated with A-752, A-759, FT A-943 and A-956." FT /evidence="ECO:0000269|PubMed:27872309, FT ECO:0000269|PubMed:35768503" FT MUTAGEN 752 FT /note="R->A: Decreased siRNA length fidelity. Abundance of FT 21-nucleotide siRNAs produced by the enzyme is decreased FT whereas the abundance of both 20- and 22-nucleotide siRNAs FT is increased. Partially rescues RNA silencing activity in FT mutants. Abolishes cleavage of 3' overhanging (3'ovr) FT termini dsRNAs but has no effect on cleavage of blunt FT termini (BLT) dsRNAs, when associated with A-743, A-759, FT A-943 and A-956." FT /evidence="ECO:0000269|PubMed:27872309, FT ECO:0000269|PubMed:35768503" FT MUTAGEN 759 FT /note="R->A: Decreased siRNA length fidelity. Abundance of FT 21-nucleotide siRNAs produced by the enzyme is decreased FT whereas the abundance of both 20- and 22-nucleotide siRNAs FT is increased. Partially rescues RNA silencing activity in FT mutants. Abolishes cleavage of 3' overhanging (3'ovr) FT termini dsRNAs but has no effect on cleavage of blunt FT termini (BLT) dsRNAs, when associated with A-743, A-752, FT A-943 and A-956." FT /evidence="ECO:0000269|PubMed:27872309, FT ECO:0000269|PubMed:32843367, ECO:0000269|PubMed:35768503" FT MUTAGEN 943 FT /note="R->A: Decreased siRNA length fidelity. Abundance of FT 21-nucleotide siRNAs produced by the enzyme is decreased FT whereas the abundance of both 20- and 22-nucleotide siRNAs FT is increased. However, has no effect on RNA cleavage rates, FT when associated with A-956. Decreased siRNA length FT fidelity, partially rescues RNA silencing activity in FT mutants and abolishes cleavage of 3' overhanging (3'ovr) FT termini dsRNAs but has no effect on cleavage of blunt FT termini (BLT) dsRNAs, when associated with A-743, A-752, FT A-759 and A-956. Abolishes binding to BLT and 3'ovr dsRNAs; FT when associated with G-225 and A-956." FT /evidence="ECO:0000269|PubMed:27872309, FT ECO:0000269|PubMed:29269422, ECO:0000269|PubMed:32843367" FT MUTAGEN 943 FT /note="R->E: Decreased siRNA length fidelity. Abundance of FT 21-nucleotide siRNAs produced by the enzyme is decreased FT whereas the abundance of both 20- and 22-nucleotide siRNAs FT is increased. However, has no effect on RNA cleavage rates, FT when associated with E-956." FT /evidence="ECO:0000269|PubMed:27872309" FT MUTAGEN 956 FT /note="R->A: Decreased siRNA length fidelity. Abundance of FT 21-nucleotide siRNAs produced by the enzyme is decreased FT whereas the abundance of both 20- and 22-nucleotide siRNAs FT is increased. However, has no effect on RNA cleavage rates FT when associated with A-943. Partially rescues RNA silencing FT activity in mutants. Abolishes cleavage of 3' overhanging FT (3'ovr) termini dsRNAs but has no effect on cleavage of FT blunt termini (BLT) dsRNAs, when associated with A-743, FT A-752, A-759 and A-943. Abolishes binding to BLT and 3'ovr FT dsRNAs; when associated with G-225 and A-493." FT /evidence="ECO:0000269|PubMed:27872309, FT ECO:0000269|PubMed:29269422, ECO:0000269|PubMed:32843367" FT MUTAGEN 956 FT /note="R->E: Decreased siRNA length fidelity. Abundance of FT 21-nucleotide siRNAs produced by the enzyme is decreased FT whereas the abundance of both 20- and 22-nucleotide siRNAs FT is increased. However, has no effect on RNA cleavage rates, FT when associated with E-943." FT /evidence="ECO:0000269|PubMed:27872309" FT MUTAGEN 1210 FT /note="E->V: No effect on RNAi silencing activity." FT /evidence="ECO:0000269|PubMed:15066283" FT MUTAGEN 1217 FT /note="D->A: Unable to unwind blunt termini (BLT) dsRNAs FT and fails to rescue loss of RNA silencing activity in FT mutants. No effect on binding to BLT or 3' overhanging FT (3'ovr) termini dsRNAs; when associated with A-1476. No FT effect on binding to 3' overhanging (3'ovr) termini but FT abolishes binding to BLT dsRNAs; when associated with A-34 FT and A-1476." FT /evidence="ECO:0000269|PubMed:25891075, FT ECO:0000269|PubMed:27872309, ECO:0000269|PubMed:29269422" FT MUTAGEN 1237 FT /note="E->A: No effect on RNAi silencing activity." FT /evidence="ECO:0000269|PubMed:15066283" FT MUTAGEN 1330 FT /note="R->A: Loss of dimerization, likely affecting FT formation of the initial binding complex with loqs and FT dsRNA." FT /evidence="ECO:0000269|PubMed:35768513" FT MUTAGEN 1371 FT /note="E->K: Loss of RNAi silencing activity. Decreased FT processing of dsRNAs into SiRNAs. No effect on mRNA FT cleavage." FT /evidence="ECO:0000269|PubMed:15066283" FT MUTAGEN 1476 FT /note="D->A: Unable to unwind blunt termini (BLT) dsRNAs FT and fails to rescue loss of RNA silencing activity in FT mutants. No effect on binding to BLT or 3' overhanging FT (3'ovr) termini dsRNAs; when associated with A-1217. No FT effect on binding to 3' overhanging (3'ovr) termini but FT abolishes binding to BLT dsRNAs; when associated with A-34 FT and A-1217." FT /evidence="ECO:0000269|PubMed:25891075, FT ECO:0000269|PubMed:27872309, ECO:0000269|PubMed:29269422" FT MUTAGEN 1617 FT /note="E->K: Loss of RNAi silencing activity. Decreased FT processing of dsRNAs into SiRNAs. No effect on mRNA FT cleavage." FT /evidence="ECO:0000269|PubMed:15066283" FT MUTAGEN 1653..1722 FT /note="Missing: Decreased RNAi silencing activity, likely FT due, at least in part, to the loss of efficient and FT high-fidelity production of 21-nucleotide siRNAs. Abolishes FT formation of siRLC and siRISC. Also displays a severe FT reduction in processing of short (30 bp) dsRNA substrates. FT Abundance and length of miRNAs, and interaction with r2d2 FT is unaffected." FT /evidence="ECO:0000269|PubMed:28416567" FT CONFLICT 134 FT /note="S -> G (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 222 FT /note="M -> L (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 254 FT /note="I -> F (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 1293 FT /note="R -> Q (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 1362 FT /note="P -> L (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 1568 FT /note="L -> P (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 1601 FT /note="N -> S (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 1671 FT /note="S -> G (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT CONFLICT 1678 FT /note="E -> G (in Ref. 1; BAB69959)" FT /evidence="ECO:0000305" FT HELIX 6..8 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 10..21 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 24..27 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 32..44 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 46..48 FT /evidence="ECO:0007829|PDB:8YII" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 53..55 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 59..66 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 67..80 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 85..88 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 90..92 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 94..96 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 99..108 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 110..115 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 116..124 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 130..132 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 133..140 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 149..155 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 156..158 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 162..164 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 167..173 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 184..194 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 197..200 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 205..211 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 212..214 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 216..218 FT /evidence="ECO:0007829|PDB:8YII" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 233..249 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:7W0B" FT STRAND 265..269 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 272..291 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 293..313 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 317..342 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 345..347 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 351..361 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 365..377 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 383..385 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 388..391 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 395..409 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 413..418 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 421..424 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 426..428 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 429..431 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 433..435 FT /evidence="ECO:0007829|PDB:7W0B" FT HELIX 446..452 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 457..463 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 466..468 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 471..473 FT /evidence="ECO:0007829|PDB:7V6C" FT STRAND 474..478 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 485..492 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 501..507 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 508..510 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 511..534 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 538..540 FT /evidence="ECO:0007829|PDB:7W0B" FT HELIX 544..551 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 555..557 FT /evidence="ECO:0007829|PDB:8YIG" FT STRAND 561..563 FT /evidence="ECO:0007829|PDB:7V6C" FT HELIX 568..570 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 571..579 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 585..587 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 589..592 FT /evidence="ECO:0007829|PDB:7W0B" FT STRAND 593..596 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 599..606 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 607..610 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 611..614 FT /evidence="ECO:0007829|PDB:7V6B" FT STRAND 616..619 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 622..625 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 632..634 FT /evidence="ECO:0007829|PDB:8YIG" FT STRAND 635..637 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 638..655 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 661..665 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 668..679 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 681..686 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 690..692 FT /evidence="ECO:0007829|PDB:8YII" FT HELIX 694..696 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 702..706 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 711..715 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 722..733 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 739..741 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 742..748 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 754..760 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 761..764 FT /evidence="ECO:0007829|PDB:8YIG" FT STRAND 768..772 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 775..781 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 786..790 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 793..805 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 806..810 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 825..827 FT /evidence="ECO:0007829|PDB:7V6B" FT STRAND 830..836 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 838..841 FT /evidence="ECO:0007829|PDB:7V6C" FT STRAND 842..844 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 846..851 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 855..858 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 863..868 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 870..872 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 874..877 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 880..883 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 885..888 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 892..901 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 906..908 FT /evidence="ECO:0007829|PDB:8YII" FT STRAND 909..911 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 917..929 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 930..932 FT /evidence="ECO:0007829|PDB:7V6B" FT STRAND 935..937 FT /evidence="ECO:0007829|PDB:7W0B" FT STRAND 939..943 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 955..957 FT /evidence="ECO:0007829|PDB:8YII" FT HELIX 961..966 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 969..971 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 973..975 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 976..982 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 983..990 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 992..1015 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 1022..1024 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1025..1027 FT /evidence="ECO:0007829|PDB:7W0B" FT HELIX 1030..1033 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 1037..1040 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 1045..1047 FT /evidence="ECO:0007829|PDB:7V6C" FT STRAND 1070..1072 FT /evidence="ECO:0007829|PDB:7V6C" FT HELIX 1076..1078 FT /evidence="ECO:0007829|PDB:7V6C" FT HELIX 1079..1083 FT /evidence="ECO:0007829|PDB:7V6C" FT HELIX 1088..1090 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 1091..1094 FT /evidence="ECO:0007829|PDB:7V6B" FT TURN 1095..1097 FT /evidence="ECO:0007829|PDB:7V6B" FT TURN 1099..1101 FT /evidence="ECO:0007829|PDB:7V6C" FT HELIX 1104..1115 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 1122..1133 FT /evidence="ECO:0007829|PDB:7W0B" FT HELIX 1145..1148 FT /evidence="ECO:0007829|PDB:7W0B" FT HELIX 1172..1174 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1175..1181 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1183..1185 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1188..1190 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1191..1198 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 1201..1203 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1210..1231 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 1232..1234 FT /evidence="ECO:0007829|PDB:8YII" FT HELIX 1237..1247 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1250..1258 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 1259..1261 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1263..1265 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1273..1276 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 1282..1284 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1286..1293 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 1296..1300 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1304..1307 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1316..1320 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1325..1336 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1337..1339 FT /evidence="ECO:0007829|PDB:7W0A" FT TURN 1342..1345 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1349..1356 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 1358..1362 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1363..1392 FT /evidence="ECO:0007829|PDB:7W0A" FT STRAND 1400..1402 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1404..1409 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1417..1419 FT /evidence="ECO:0007829|PDB:7W0B" FT HELIX 1423..1429 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1433..1440 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1448..1454 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1462..1465 FT /evidence="ECO:0007829|PDB:8YII" FT HELIX 1469..1490 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1496..1506 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1509..1518 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1522..1524 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1530..1546 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1552..1556 FT /evidence="ECO:0007829|PDB:7V6B" FT TURN 1560..1562 FT /evidence="ECO:0007829|PDB:7V6C" FT HELIX 1607..1609 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1610..1627 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1630..1648 FT /evidence="ECO:0007829|PDB:7W0A" FT HELIX 1652..1655 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 1656..1661 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 1663..1665 FT /evidence="ECO:0007829|PDB:7W0B" FT STRAND 1678..1680 FT /evidence="ECO:0007829|PDB:7W0B" FT STRAND 1684..1688 FT /evidence="ECO:0007829|PDB:7V6B" FT STRAND 1691..1695 FT /evidence="ECO:0007829|PDB:7V6B" FT HELIX 1702..1719 FT /evidence="ECO:0007829|PDB:7V6B" SQ SEQUENCE 1722 AA; 197765 MW; 73755021033C399A CRC64; MEDVEIKPRG YQLRLVDHLT KSNGIVYLPT GSGKTFVAIL VLKRFSQDFD KPIESGGKRA LFMCNTVELA RQQAMAVRRC TNFKVGFYVG EQGVDDWTRG MWSDEIKKNQ VLVGTAQVFL DMVTQTYVAL SSLSVVIIDE CHHGTGHHPF REFMRLFTIA NQTKLPRVVG LTGVLIKGNE ITNVATKLKE LEITYRGNII TVSDTKEMEN VMLYATKPTE VMVSFPHQEQ VLTVTRLISA EIEKFYVSLD LMNIGVQPIR RSKSLQCLRD PSKKSFVKQL FNDFLYQMKE YGIYAASIAI ISLIVEFDIK RRQAETLSVK LMHRTALTLC EKIRHLLVQK LQDMTYDDDD DNVNTEEVIM NFSTPKVQRF LMSLKVSFAD KDPKDICCLV FVERRYTCKC IYGLLLNYIQ STPELRNVLT PQFMVGRNNI SPDFESVLER KWQKSAIQQF RDGNANLMIC SSVLEEGIDV QACNHVFILD PVKTFNMYVQ SKGRARTTEA KFVLFTADKE REKTIQQIYQ YRKAHNDIAE YLKDRVLEKT EPELYEIKGH FQDDIDPFTN ENGAVLLPNN ALAILHRYCQ TIPTDAFGFV IPWFHVLQED ERDRIFGVSA KGKHVISINM PVNCMLRDTI YSDPMDNVKT AKISAAFKAC KVLYSLGELN ERFVPKTLKE RVASIADVHF EHWNKYGDSV TATVNKADKS KDRTYKTECP LEFYDALPRV GEICYAYEIF LEPQFESCEY TEHMYLNLQT PRNYAILLRN KLPRLAEMPL FSNQGKLHVR VANAPLEVII QNSEQLELLH QFHGMVFRDI LKIWHPFFVL DRRSKENSYL VVPLILGAGE QKCFDWELMT NFRRLPQSHG SNVQQREQQP APRPEDFEGK IVTQWYANYD KPMLVTKVHR ELTPLSYMEK NQQDKTYYEF TMSKYGNRIG DVVHKDKFMI EVRDLTEQLT FYVHNRGKFN AKSKAKMKVI LIPELCFNFN FPGDLWLKLI FLPSILNRMY FLLHAEALRK RFNTYLNLHL LPFNGTDYMP RPLEIDYSLK RNVDPLGNVI PTEDIEEPKS LLEPMPTKSI EASVANLEIT EFENPWQKYM EPVDLSRNLL STYPVELDYY YHFSVGNVCE MNEMDFEDKE YWAKNQFHMP TGNIYGNRTP AKTNANVPAL MPSKPTVRGK VKPLLILQKT VSKEHITPAE QGEFLAAITA SSAADVFDME RLEILGDSFL KLSATLYLAS KYSDWNEGTL TEVKSKLVSN RNLLFCLIDA DIPKTLNTIQ FTPRYTWLPP GISLPHNVLA LWRENPEFAK IIGPHNLRDL ALGDEESLVK GNCSDINYNR FVEGCRANGQ SFYAGADFSS EVNFCVGLVT IPNKVIADTL EALLGVIVKN YGLQHAFKML EYFKICRADI DKPLTQLLNL ELGGKKMRAN VNTTEIDGFL INHYYLEKNL GYTFKDRRYL LQALTHPSYP TNRITGSYQE LEFIGDAILD FLISAYIFEN NTKMNPGALT DLRSALVNNT TLACICVRHR LHFFILAENA KLSEIISKFV NFQESQGHRV TNYVRILLEE ADVQPTPLDL DDELDMTELP HANKCISQEA EKGVPPKGEF NMSTNVDVPK ALGDVLEALI AAVYLDCRDL QRTWEVIFNL FEPELQEFTR KVPINHIRQL VEHKHAKPVF SSPIVEGETV MVSCQFTCME KTIKVYGFGS NKDQAKLSAA KHALQQLSKC DA //