ID DCR1_DROME Reviewed; 2249 AA. AC Q9VCU9; Q961S7; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 175. DE RecName: Full=Endoribonuclease Dcr-1 {ECO:0000303|PubMed:17666393}; DE Short=Protein dicer-1 {ECO:0000303|PubMed:15066283}; DE EC=3.1.26.3 {ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:15918769, ECO:0000269|PubMed:17666393, ECO:0000269|PubMed:21926993}; GN Name=Dcr-1 {ECO:0000303|PubMed:17666393, GN ECO:0000312|FlyBase:FBgn0039016}; GN ORFNames=CG4792 {ECO:0000312|FlyBase:FBgn0039016}; 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:0000312|EMBL:AAF56056.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132}; 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] {ECO:0000305, ECO:0000312|EMBL:AAF56056.1} 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] {ECO:0000305, ECO:0000312|EMBL:AAK84929.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1338-2249. RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569}; RC TISSUE=Embryo {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 [4] {ECO:0000305} RP FUNCTION. RX PubMed=11201747; DOI=10.1038/35053110; RA Bernstein E., Caudy A.A., Hammond S.M., Hannon G.J.; RT "Role for a bidentate ribonuclease in the initiation step of RNA RT interference."; RL Nature 409:363-366(2001). RN [5] {ECO:0000305} RP FUNCTION, AND INTERACTION WITH AGO2. RX PubMed=11498593; DOI=10.1126/science.1064023; RA Hammond S.M., Boettcher S., Caudy A.A., Kobayashi R., Hannon G.J.; RT "Argonaute2, a link between genetic and biochemical analyses of RNAi."; RL Science 293:1146-1150(2001). RN [6] {ECO:0000305} RP INTERACTION WITH FMR1. RX PubMed=12368261; DOI=10.1101/gad.1022002; RA Ishizuka A., Siomi M.C., Siomi H.; RT "A Drosophila fragile X protein interacts with components of RNAi and RT ribosomal proteins."; RL Genes Dev. 16:2497-2508(2002). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. 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 [8] RP FUNCTION, INTERACTION WITH LOQS (ISOFORM PB), AND SUBCELLULAR LOCATION. RX PubMed=15985611; DOI=10.1101/gad.1334005; RA Jiang F., Ye X., Liu X., Fincher L., McKearin D., Liu Q.; RT "Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila."; RL Genes Dev. 19:1674-1679(2005). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, IDENTIFICATION IN THE MIRNA-RISC RP LOADING COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=15918769; DOI=10.1371/journal.pbio.0030235; RA Saito K., Ishizuka A., Siomi H., Siomi M.C.; RT "Processing of pre-microRNAs by the Dicer-1-Loquacious complex in RT Drosophila cells."; RL PLoS Biol. 3:e235-e235(2005). RN [10] RP FUNCTION, AND INTERACTION WITH PIWI AND VAS. RX PubMed=16949822; DOI=10.1016/j.cub.2006.08.051; RA Megosh H.B., Cox D.N., Campbell C., Lin H.; RT "The role of PIWI and the miRNA machinery in Drosophila germline RT determination."; RL Curr. Biol. 16:1884-1894(2006). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LOQS (ISOFORMS PA; PB AND RP PC), DOMAIN, AND MUTAGENESIS OF ASP-1749; GLU-1908; ASP-2036; GLU-2139 AND RP 2186-LEU--ASP-2249. RX PubMed=17666393; DOI=10.1074/jbc.m705208200; RA Ye X., Paroo Z., Liu Q.; RT "Functional anatomy of the Drosophila microRNA-generating enzyme."; RL J. Biol. Chem. 282:28373-28378(2007). RN [12] RP FUNCTION. RX PubMed=17928574; DOI=10.1261/rna.723707; RA Liu X., Park J.K., Jiang F., Liu Y., McKearin D., Liu Q.; RT "Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced RT silencing complexes."; RL RNA 13:2324-2329(2007). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1423; SER-1877 AND SER-1880, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryo; 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 [14] RP FUNCTION, AND IDENTIFICATION IN THE MIRNA-RISC LOADING COMPLEX. RX PubMed=19451544; DOI=10.1261/rna.1541209; RA Miyoshi K., Okada T.N., Siomi H., Siomi M.C.; RT "Characterization of the miRNA-RISC loading complex and miRNA-RISC formed RT in the Drosophila miRNA pathway."; RL RNA 15:1282-1291(2009). RN [15] RP FUNCTION, AND INTERACTION WITH LOQS (ISOFORMS PA AND PB). 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 [16] RP FUNCTION, AND ACTIVITY REGULATION. 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 [17] RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF GLU-1908 AND RP GLU-2139. RX PubMed=21926993; DOI=10.1038/nsmb.2125; RA Tsutsumi A., Kawamata T., Izumi N., Seitz H., Tomari Y.; RT "Recognition of the pre-miRNA structure by Drosophila Dicer-1."; RL Nat. Struct. Mol. Biol. 18:1153-1158(2011). RN [18] 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 [19] RP FUNCTION, AND ACTIVITY REGULATION. 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 [20] {ECO:0007744|PDB:8DFV, ECO:0007744|PDB:8DG5, ECO:0007744|PDB:8DG7, ECO:0007744|PDB:8DGA, ECO:0007744|PDB:8DGI, ECO:0007744|PDB:8DGJ} RP STRUCTURE BY ELECTRON MICROSCOPY (3.06 ANGSTROMS) IN COMPLEX WITH LOQS RP (ISOFORM PB), FUNCTION, INTERACTION WITH LOQS (ISOFORM PB), COFACTOR, AND RP DOMAIN. RX PubMed=36182693; DOI=10.1016/j.molcel.2022.09.002; RA Jouravleva K., Golovenko D., Demo G., Dutcher R.C., Hall T.M.T., RA Zamore P.D., Korostelev A.A.; RT "Structural basis of microRNA biogenesis by Dicer-1 and its partner protein RT Loqs-PB."; RL Mol. Cell 82:4049-4063.e6(2022). CC -!- FUNCTION: Endoribonuclease which functions in microRNA- (miRNA) gene CC silencing and, independently of its ribonuclease III activity, also CC acts in the short interfering RNA- (siRNA) gene silencing pathway CC (PubMed:11201747, PubMed:11498593, PubMed:15066283, PubMed:15985611, CC PubMed:24488111, PubMed:17666393, PubMed:17928574, PubMed:19451544, CC PubMed:15918769, PubMed:21926993, PubMed:21419681, PubMed:36182693, CC PubMed:19635780). Cleaves hairpin precursor miRNAs (pre-miRNA) to CC generate mature miRNAs (miRNAs) that are between twenty-one to twenty- CC four nucleotides in length and function in RNA silencing and post- CC transcriptional regulation of gene expression (PubMed:15066283, CC PubMed:15985611, PubMed:24488111, PubMed:17666393, PubMed:17928574, CC PubMed:19451544, PubMed:21419681, PubMed:15918769, PubMed:21926993, CC PubMed:36182693, PubMed:19635780, PubMed:23063653). Also functions in CC miRNA loading and assembly of the Argonaute 1 (AGO1)-containing RNA- CC induced silencing complex (miRISC), with the miRNAs serving as a guide CC to direct the miRISC to complementary RNAs to degrade them or prevent CC their translation (PubMed:15066283, PubMed:19451544, PubMed:17928574). CC Independently of its catalytic activity, functions in the siRNA CC silencing pathway by promoting assembly of the siRNA-directed Argonaute CC 2 (AGO2)-containing RISC (siRISC) (PubMed:15066283). Required for the CC proper formation of a stable intermediate (R2) in siRISC assembly, CC which is formed from the R1 precursor complex (containing Dcr-2, R2D2 CC and the siRNA) and is used for assembly of the mature (R3) siRISC CC complex (PubMed:15066283). It is not required for siRNA biogenesis CC (PubMed:15066283, PubMed:21419681). During embryogenesis, involved in CC germline fate determination (PubMed:16949822). CC {ECO:0000269|PubMed:11201747, ECO:0000269|PubMed:11498593, CC ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:15918769, CC ECO:0000269|PubMed:15985611, ECO:0000269|PubMed:16949822, CC ECO:0000269|PubMed:17666393, ECO:0000269|PubMed:17928574, CC ECO:0000269|PubMed:19451544, ECO:0000269|PubMed:19635780, CC ECO:0000269|PubMed:21419681, ECO:0000269|PubMed:21926993, CC ECO:0000269|PubMed:23063653, ECO:0000269|PubMed:24488111, CC ECO:0000269|PubMed:36182693}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3; CC Evidence={ECO:0000269|PubMed:15066283, ECO:0000269|PubMed:15918769, CC ECO:0000269|PubMed:17666393, ECO:0000269|PubMed:21926993}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:15918769, ECO:0000269|PubMed:36182693}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activity towards pre-miRNAs is not inhibited by CC inorganic phosphate. {ECO:0000269|PubMed:21419681, CC ECO:0000269|PubMed:24488111}. CC -!- SUBUNIT: Component of the miRNA-directed RISC loading complex (miRLC), CC composed of at least Dcr-1, AGO1 and loqs, which processes pre-miRNAs CC and loads the resulting miRNAs into the Argonaute 1 (AGO1)-containing CC RNA-induced silencing complex (miRISC) (PubMed:19451544, CC PubMed:15918769). Interacts (via helicase domain) with dicing cofactor CC loqs isoform-PB (loqs-PB) (via DRBM 3 domain); this interaction CC enhances processing of pre-miRNAs by increasing substrate binding CC affinity of the dicer (PubMed:17666393, PubMed:36182693, CC PubMed:15985611, PubMed:19635780). Also able to interact with loqs CC isoforms PA and PC, however the relevance of such interactions are CC unclear in vivo (PubMed:17666393, PubMed:19635780). Different regions CC of the Dcr-1-loqs-PB heterodimer collaborate to recognize, bind and CC position the pre-miRNA for Dcr-1 mediated cleavage (PubMed:36182693). CC In the absence of authentic miRNA substrates, the heterodimer favors a CC closed, catalytically incompetent, conformation, whereas binding of CC authentic pre-miRNA substrates stabilizes the relatively rare open, CC catalytically competent, conformation of the heterodimer CC (PubMed:36182693). During substrate recognition, the Dcr-1 PAZ domain CC and pre-miRNA interact with the DRBM 1 domain of loqs-PB, which likely CC contributes to substrate recognition and stabilization CC (PubMed:36182693). At the miRNA binding stage, the Dcr-1 DRBM domain CC and loqs-PB DRBM domains then bind the pre-miRNA in tandem to form a CC tight 'belt' around the pre-miRNA stem, the pre-miRNA loop is docked in CC the loop-binding region formed by DUF283, DRBM and part of the N CC terminus of Dcr-1, and the loqs-PB DRBM 1 and the wing domain of Dcr-1 CC act together to bind the 5' and 3' pre-miRNA termini within the PAZ and CC platform domains of Dcr-1 (PubMed:36182693). These interactions between CC the proteins and their pre-miRNA substrate stabilize a distorted form CC of the pre-miRNA and position the scissile phosphodiester bonds of the CC pre-miRNA at the RNase III catalytic cleavage sites of Dcr-1 CC (PubMed:36182693). Following Dcr-1 mediated cleavage, the miRNA duplex CC remains bound to loqs-PB DRBM 1, which dissociates from the Dcr-1 RNase CC III 1 domain but remains in contact with the PAZ and wing domains, CC suggesting that the heterodimer presents the mature miRNA to Ago2 for CC loading into the RNA-induced silencing complex (miRISC) CC (PubMed:36182693). Interacts with AGO2 and Fmr1 to form a RNA-induced CC silencing complex (siRISC), a ribonucleoprotein (RNP) complex involved CC in translation regulation; other components of the complex are RpL5, CC RpL11, AGO2 and Rm62 (PubMed:11498593, PubMed:12368261). Interacts with CC piwi and vas; these interactions occur in the polar granules CC (PubMed:16949822). {ECO:0000269|PubMed:11498593, CC ECO:0000269|PubMed:12368261, ECO:0000269|PubMed:15918769, CC ECO:0000269|PubMed:15985611, ECO:0000269|PubMed:16949822, CC ECO:0000269|PubMed:17666393, ECO:0000269|PubMed:19451544, CC ECO:0000269|PubMed:19635780, ECO:0000269|PubMed:36182693}. CC -!- INTERACTION: CC Q9VCU9; Q8IP72: loqs; NbExp=4; IntAct=EBI-112170, EBI-162836; CC Q9VCU9; Q9VJY9: loqs; NbExp=12; IntAct=EBI-112170, EBI-638074; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15918769}. CC Cytoplasm, cytosol {ECO:0000303|PubMed:15985611}. CC -!- DOMAIN: The helicase domain is essential for substrate discrimination CC (PubMed:21926993). Probably identifies authentic miRNA substrates, by CC binding to the miRNA characteristic single-stranded terminal loop, CC checking the loop size, and measuring the distance between the terminal CC loop and the 3' overhanging (3'ovr) termini which is bound by the PAZ CC domain (PubMed:21926993). {ECO:0000269|PubMed:21926993}. CC -!- DOMAIN: The PAZ domain is important for substrate discrimination as it CC recognizes and binds the characteristic two-nucleotide, 3' overhanging CC (3'ovr) termini of pre-miRNA substrates prior to cleavage CC (PubMed:36182693). The PAZ and platform domains form a binding pocket CC that binds the 5' terminal nucleotide of the pre-miRNA CC (PubMed:36182693). {ECO:0000269|PubMed:36182693}. CC -!- DOMAIN: RNase III 1 domain is necessary for cleaving the 3' (bottom) CC strand of pre-miRNA hairpins (pri-let-7) (PubMed:17666393, CC PubMed:36182693). Together with the RNase III 2 domain forms a cleavage CC processing center with the RNase III 1 and RNase III 2 domains cutting CC the 3' (bottom) and 5' (top) strand respectively, excising the miRNA CC from the pre-miRNA pri-let-7 and creating the characteristic two- CC nucleotide 3' overhang terminus (PubMed:17666393, PubMed:36182693). CC {ECO:0000269|PubMed:17666393, ECO:0000269|PubMed:36182693}. CC -!- DOMAIN: RNase III 2 domain is necessary for cleaving the 5' (top) CC strand of pre-miRNA hairpins (pri-let-7) (PubMed:17666393, CC PubMed:36182693). Together with the RNase III 1 domain forms a cleavage CC processing center with the RNase III 1 and RNase III 2 domains cutting CC the 3' (bottom) and 5' (top) strand respectively, excising the miRNA CC from the pre-miRNA pri-let-7 and creating the characteristic two- CC nucleotide 3' overhang terminus (PubMed:17666393, PubMed:36182693). CC {ECO:0000269|PubMed:17666393, ECO:0000269|PubMed:36182693}. CC -!- DOMAIN: Within the closed conformation of the Dcr-1-loqs-PB CC heterodimer, the DRBM domain blocks access of pre-miRNA substrates to CC the RNase III active sites. {ECO:0000269|PubMed:36182693}. CC -!- SIMILARITY: Belongs to the helicase family. Dicer subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00657}. CC -!- SEQUENCE CAUTION: CC Sequence=AAK84929.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AAF56056.1; -; Genomic_DNA. DR EMBL; AY050230; AAK84929.1; ALT_INIT; mRNA. DR RefSeq; NP_524453.1; NM_079729.3. DR PDB; 8DFV; EM; 3.06 A; A=1-2249. DR PDB; 8DG5; EM; 3.26 A; A=1-2249. DR PDB; 8DG7; EM; 3.32 A; A=1-2249. DR PDB; 8DGA; EM; 3.73 A; A=1-2249. DR PDB; 8DGI; EM; 3.94 A; A=1-2249. DR PDB; 8DGJ; EM; 4.02 A; A=1-2249. DR PDBsum; 8DFV; -. DR PDBsum; 8DG5; -. DR PDBsum; 8DG7; -. DR PDBsum; 8DGA; -. DR PDBsum; 8DGI; -. DR PDBsum; 8DGJ; -. DR AlphaFoldDB; Q9VCU9; -. DR EMDB; EMD-27415; -. DR EMDB; EMD-27416; -. DR EMDB; EMD-27417; -. DR EMDB; EMD-27420; -. DR EMDB; EMD-27423; -. DR EMDB; EMD-27427; -. DR EMDB; EMD-7292; -. DR SMR; Q9VCU9; -. DR BioGRID; 67642; 24. DR ComplexPortal; CPX-2737; miRNA RISC-loading complex. DR DIP; DIP-23028N; -. DR IntAct; Q9VCU9; 11. DR STRING; 7227.FBpp0083717; -. DR iPTMnet; Q9VCU9; -. DR PaxDb; 7227-FBpp0083717; -. DR EnsemblMetazoa; FBtr0084324; FBpp0083717; FBgn0039016. DR GeneID; 42693; -. DR KEGG; dme:Dmel_CG4792; -. DR UCSC; CG4792-RA; d. melanogaster. DR AGR; FB:FBgn0039016; -. DR CTD; 42693; -. DR FlyBase; FBgn0039016; Dcr-1. DR VEuPathDB; VectorBase:FBgn0039016; -. DR eggNOG; KOG0701; Eukaryota. DR GeneTree; ENSGT00940000156287; -. DR HOGENOM; CLU_000907_4_4_1; -. DR InParanoid; Q9VCU9; -. DR OMA; LCAIHPF; -. DR OrthoDB; 342391at2759; -. DR PhylomeDB; Q9VCU9; -. DR Reactome; R-DME-203927; MicroRNA (miRNA) biogenesis. DR Reactome; R-DME-426486; Small interfering RNA (siRNA) biogenesis. DR SignaLink; Q9VCU9; -. DR BioGRID-ORCS; 42693; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 42693; -. DR PRO; PR:Q9VCU9; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0039016; Expressed in eye disc (Drosophila) and 23 other cell types or tissues. DR ExpressionAtlas; Q9VCU9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0016442; C:RISC complex; ISS:UniProtKB. DR GO; GO:0070578; C:RISC-loading complex; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016443; F:bidentate ribonuclease III activity; IDA:FlyBase. DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central. DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0070883; F:pre-miRNA binding; IDA:FlyBase. DR GO; GO:0004525; F:ribonuclease III activity; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0003727; F:single-stranded RNA binding; IDA:FlyBase. DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase. DR GO; GO:0033227; P:dsRNA transport; IMP:FlyBase. DR GO; GO:0042078; P:germ-line stem cell division; IMP:FlyBase. DR GO; GO:0030727; P:germarium-derived female germ-line cyst formation; IMP:FlyBase. DR GO; GO:0007294; P:germarium-derived oocyte fate determination; IMP:FlyBase. DR GO; GO:0035196; P:miRNA processing; IMP:FlyBase. DR GO; GO:0045448; P:mitotic cell cycle, embryonic; IMP:FlyBase. DR GO; GO:0007279; P:pole cell formation; IMP:FlyBase. DR GO; GO:0031054; P:pre-miRNA processing; IDA:FlyBase. DR GO; GO:0035194; P:regulatory ncRNA-mediated post-transcriptional gene silencing; IMP:FlyBase. DR GO; GO:0042594; P:response to starvation; IMP:FlyBase. DR GO; GO:0070922; P:RISC complex assembly; IMP:FlyBase. DR GO; GO:0007367; P:segment polarity determination; IGI:FlyBase. DR GO; GO:0030422; P:siRNA processing; IDA:UniProtKB. DR CDD; cd15903; Dicer_PBD; 1. DR CDD; cd10843; DSRM_DICER; 1. DR CDD; cd02843; PAZ_dicer_like; 1. DR CDD; cd00593; RIBOc; 2. 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; IPR038248; Dicer_dimer_sf. DR InterPro; IPR005034; Dicer_dimerisation_dom. DR InterPro; IPR044441; DICER_DSRM. DR InterPro; IPR048513; Dicer_PBD. DR InterPro; IPR048512; Dicer_platform. DR InterPro; IPR014720; dsRBD_dom. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR003100; PAZ_dom. DR InterPro; IPR036085; PAZ_dom_sf. DR InterPro; IPR000999; RNase_III_dom. DR InterPro; IPR036389; RNase_III_sf. DR PANTHER; PTHR14950; DICER-RELATED; 1. DR PANTHER; PTHR14950:SF37; ENDORIBONUCLEASE DICER; 1. DR Pfam; PF03368; Dicer_dimer; 1. DR Pfam; PF20932; Dicer_dsRBD; 1. DR Pfam; PF20930; Dicer_PBD; 1. DR Pfam; PF20931; Dicer_platform; 1. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF00636; Ribonuclease_3; 2. 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; SSF101690; PAZ domain; 1. DR SUPFAM; SSF69065; RNase III domain-like; 2. DR PROSITE; PS51327; DICER_DSRBF; 1. DR PROSITE; PS50137; DS_RBD; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS00517; RNASE_3_1; 1. DR PROSITE; PS50142; RNASE_3_2; 2. DR Genevisible; Q9VCU9; DM. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cytoplasm; Endonuclease; Helicase; Hydrolase; KW Magnesium; Manganese; Metal-binding; Nuclease; Nucleotide-binding; KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; KW RNA-mediated gene silencing. FT CHAIN 1..2249 FT /note="Endoribonuclease Dcr-1" FT /id="PRO_0000180474" FT DOMAIN 485..648 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT DOMAIN 825..920 FT /note="Dicer dsRNA-binding fold" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00657" FT DOMAIN 1100..1246 FT /note="PAZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142" FT DOMAIN 1698..1919 FT /note="RNase III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177" FT DOMAIN 1993..2150 FT /note="RNase III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00177" FT DOMAIN 2175..2241 FT /note="DRBM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266" FT REGION 1..1042 FT /note="Necessary for processing certain pre-miRNas, such as FT pre-let 7 and pre-bantam" FT /evidence="ECO:0000269|PubMed:17666393" FT REGION 1..761 FT /note="Helicase domain" FT /evidence="ECO:0000250|UniProtKB:A1ZAW0" FT REGION 1..690 FT /note="Important for interaction with loqs isoform PB FT (loqs-PB)" FT /evidence="ECO:0000269|PubMed:17666393" FT REGION 1..371 FT /note="Essential for miRNA substrate recognition" FT /evidence="ECO:0000269|PubMed:21926993" FT REGION 371..491 FT /note="Dispensable for activity and substrate recognition" FT /evidence="ECO:0000269|PubMed:21926993" FT REGION 436..486 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 496..606 FT /note="Essential for miRNA substrate recognition" FT /evidence="ECO:0000269|PubMed:21926993" FT REGION 617..761 FT /note="Dispensable for activity and substrate recognition" FT /evidence="ECO:0000269|PubMed:21926993" FT REGION 640..665 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 705..757 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 924..957 FT /note="Wing domain" FT /evidence="ECO:0000269|PubMed:36182693" FT REGION 963..1108 FT /note="Platform domain" FT /evidence="ECO:0000250|UniProtKB:A1ZAW0" FT REGION 1147..2249 FT /note="Essential for production of mature miRNAs from pre- FT miRNAs. Also important for proper formation of the siRISC FT complex but is dispensable for biogenesis of siRNAs" FT /evidence="ECO:0000269|PubMed:15066283" FT REGION 1314..1351 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1426..1477 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 649..665 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1426..1448 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 37..44 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT BINDING 1745 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:36182693, FT ECO:0007744|PDB:8DG7" FT BINDING 1749 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:36182693, FT ECO:0007744|PDB:8DG5, ECO:0007744|PDB:8DG7" FT BINDING 1905 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:36182693, FT ECO:0007744|PDB:8DG7" FT BINDING 1908 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:36182693, FT ECO:0007744|PDB:8DG7" FT BINDING 1908 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:36182693, FT ECO:0007744|PDB:8DG7" FT BINDING 2032 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q9UPY3" FT BINDING 2136 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q9UPY3" FT BINDING 2139 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q9UPY3" FT SITE 2132 FT /note="Important for activity" FT /evidence="ECO:0000250" FT MOD_RES 1423 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18327897" FT MOD_RES 1877 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18327897" FT MOD_RES 1880 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18327897" FT MUTAGEN 1749 FT /note="D->A: Cleaves the 5' (top) strand but not the 3' FT (bottom) strand of pre-miRNA." FT /evidence="ECO:0000269|PubMed:17666393" FT MUTAGEN 1908 FT /note="E->A: Cleaves the 5' (top) strand but not the 3' FT (bottom) strand of pre-miRNA. Abolishes cleavage of FT pre-miRNA; when associated with A-2139." FT /evidence="ECO:0000269|PubMed:17666393, FT ECO:0000269|PubMed:21926993" FT MUTAGEN 2036 FT /note="D->A: Cleaves the 3' (bottom) strand but not the 5' FT (top) strand of pre-miRNA." FT /evidence="ECO:0000269|PubMed:17666393" FT MUTAGEN 2139 FT /note="E->A: Cleaves the 3' (bottom) strand but not the 5' FT (top) strand of pre-miRNA. Abolishes cleavage of pre-miRNA; FT when associated with A-1908." FT /evidence="ECO:0000269|PubMed:17666393, FT ECO:0000269|PubMed:21926993" FT MUTAGEN 2186..2249 FT /note="Missing: No effect on processing of the pre-miRNas, FT pre-let 7 and pre-bantam." FT /evidence="ECO:0000269|PubMed:17666393" FT CONFLICT 1338..1339 FT /note="PT -> AI (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 1345 FT /note="L -> I (in Ref. 3)" FT /evidence="ECO:0000305" SQ SEQUENCE 2249 AA; 255330 MW; D693F0432AC8033D CRC64; MAFHWCDNNL HTTVFTPRDF QVELLATAYE RNTIICLGHR SSKEFIALKL LQELSRRARR HGRVSVYLSC EVGTSTEPCS IYTMLTHLTD LRVWQEQPDM QIPFDHCWTD YHVSILRPEG FLYLLETREL LLSSVELIVL EDCHDSAVYQ RIRPLFENHI MPAPPADRPR ILGLAGPLHS AGCELQQLSA MLATLEQSVL CQIETASDIV TVLRYCSRPH EYIVQCAPFE MDELSLVLAD VLNTHKSFLL DHRYDPYEIY GTDQFMDELK DIPDPKVDPL NVINSLLVVL HEMGPWCTQR AAHHFYQCNE KLKVKTPHER HYLLYCLVST ALIQLYSLCE HAFHRHLGSG SDSRQTIERY SSPKVRRLLQ TLRCFKPEEV HTQADGLRRM RHQVDQADFN RLSHTLESKC RMVDQMDQPP TETRALVATL EQILHTTEDR QTNRSAARVT PTPTPAHAKP KPSSGANTAQ PRTRRRVYTR RHHRDHNDGS DTLCALIYCN QNHTARVLFE LLAEISRRDP DLKFLRCQYT TDRVADPTTE PKEAELEHRR QEEVLKRFRM HDCNVLIGTS VLEEGIDVPK CNLVVRWDPP TTYRSYVQCK GRARAAPAYH VILVAPSYKS PTVGSVQLTD RSHRYICATG DTTEADSDSD DSAMPNSSGS DPYTFGTARG TVKILNPEVF SKQPPTACDI KLQEIQDELP AAAQLDTSNS SDEAVSMSNT SPSESSTEQK SRRFQCELSS LTEPEDTSDT TAEIDTAHSL ASTTKDLVHQ MAQYREIEQM LLSKCANTEP PEQEQSEAER FSACLAAYRP KPHLLTGASV DLGSAIALVN KYCARLPSDT FTKLTALWRC TRNERAGVTL FQYTLRLPIN SPLKHDIVGL PMPTQTLARR LAALQACVEL HRIGELDDQL QPIGKEGFRA LEPDWECFEL EPEDEQIVQL SDEPRPGTTK RRQYYYKRIA SEFCDCRPVA GAPCYLYFIQ LTLQCPIPEE QNTRGRKIYP PEDAQQGFGI LTTKRIPKLS AFSIFTRSGE VKVSLELAKE RVILTSEQIV CINGFLNYTF TNVLRLQKFL MLFDPDSTEN CVFIVPTVKA PAGGKHIDWQ FLELIQANGN TMPRAVPDEE RQAQPFDPQR FQDAVVMPWY RNQDQPQYFY VAEICPHLSP LSCFPGDNYR TFKHYYLVKY GLTIQNTSQP LLDVDHTSAR LNFLTPRYVN RKGVALPTSS EETKRAKREN LEQKQILVPE LCTVHPFPAS LWRTAVCLPC ILYRINGLLL ADDIRKQVSA DLGLGRQQIE DEDFEWPMLD FGWSLSEVLK KSRESKQKES LKDDTINGKD LADVEKKPTS EETQLDKDSK DDKVEKSAIE LIIEGEEKLQ EADDFIEIGT WSNDMADDIA SFNQEDDDED DAFHLPVLPA NVKFCDQQTR YGSPTFWDVS NGESGFKGPK SSQNKQGGKG KAKGPAKPTF NYYDSDNSLG SSYDDDDNAG PLNYMHHNYS SDDDDVADDI DAGRIAFTSK NEAETIETAQ EVEKRQKQLS IIQATNANER QYQQTKNLLI GFNFKHEDQK EPATIRYEES IAKLKTEIES GGMLVPHDQQ LVLKRSDAAE AQVAKVSMME LLKQLLPYVN EDVLAKKLGD RRELLLSDLV ELNADWVARH EQETYNVMGC GDSFDNYNDH HRLNLDEKQL KLQYERIEIE PPTSTKAITS AILPAGFSFD RQPDLVGHPG PSPSIILQAL TMSNANDGIN LERLETIGDS FLKYAITTYL YITYENVHEG KLSHLRSKQV ANLNLYRLGR RKRLGEYMIA TKFEPHDNWL PPCYYVPKEL EKALIEAKIP THHWKLADLL DIKNLSSVQI CEMVREKADA LGLEQNGGAQ NGQLDDSNDS CNDFSCFIPY NLVSQHSIPD KSIADCVEAL IGAYLIECGP RGALLFMAWL GVRVLPITRQ LDGGNQEQRI PGSTKPNAEN VVTVYGAWPT PRSPLLHFAP NATEELDQLL SGFEEFEESL GYKFRDRSYL LQAMTHASYT PNRLTDCYQR LEFLGDAVLD YLITRHLYED PRQHSPGALT DLRSALVNNT IFASLAVRHG FHKFFRHLSP GLNDVIDRFV RIQQENGHCI SEEYYLLSEE ECDDAEDVEV PKALGDVFES IAGAIFLDSN MSLDVVWHVY SNMMSPEIEQ FSNSVPKSPI RELLELEPET AKFGKPEKLA DGRRVRVTVD VFCKGTFRGI GRNYRIAKCT AAKCALRQLK KQGLIAKKD //