ID AGO2_DROME Reviewed; 1214 AA. AC Q9VUQ5; C7LAD2; Q2Q3Y0; Q2Q3Y1; Q2Q3Y3; Q2Q3Y4; Q2Q3Y5; Q86P07; Q8T3N2; AC Q9VUQ6; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 3. DT 27-MAR-2024, entry version 170. DE RecName: Full=Protein argonaute-2; GN Name=AGO2 {ECO:0000312|EMBL:AAF49620.2}; ORFNames=CG7439; 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:AAF49620.2} 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:AAF49619.2} RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING. 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:AAO39550.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B AND C). RC STRAIN=Berkeley {ECO:0000312|EMBL:AAO39550.1}; TISSUE=Embryo; RA Stapleton M., Brokstein P., Hong L., Agbayani A., Booth B., Carlson J.W., RA Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., RA George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., RA Miranda A., Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., RA Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., RA Celniker S.E.; RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 376-1214, AND VARIANTS ARG-714; RP PRO-740; ASN-783; ALA-835; THR-854 AND GLU-866. RC STRAIN=128, 130, 138, 140, 141, 186, 187, and 196; RX PubMed=16546082; DOI=10.1016/j.cub.2006.01.065; RA Obbard D.J., Jiggins F.M., Halligan D.L., Little T.J.; RT "Natural selection drives extremely rapid evolution in antiviral RNAi RT genes."; RL Curr. Biol. 16:580-585(2006). RN [5] {ECO:0000305, ECO:0000312|EMBL:AAM11104.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 449-1214, AND VARIANTS ASN-783; RP ALA-835 AND THR-854. RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569}; RC TISSUE=Ovary {ECO:0000269|PubMed:12537569}; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [6] {ECO:0000305} RP PROTEIN SEQUENCE OF 506-515; 525-531; 554-557; 617-627; 662-674; 809-815 RP AND 1181-1188 (ISOFORM B), FUNCTION, AND INTERACTION WITH DCR-1. 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 [7] RP FUNCTION, AND INTERACTION WITH VIG; FMR1 AND TUDOR-SN. RX PubMed=14508492; DOI=10.1038/nature01956; RA Caudy A.A., Ketting R.F., Hammond S.M., Denli A.M., Bathoorn A.M., RA Tops B.B., Silva J.M., Myers M.M., Hannon G.J., Plasterk R.H.; RT "A micrococcal nuclease homologue in RNAi effector complexes."; RL Nature 425:411-414(2003). RN [8] {ECO:0000305} RP FUNCTION, AND 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 [9] RP SUBCELLULAR LOCATION. RX PubMed=17178403; DOI=10.1016/j.neuron.2006.10.028; RA Barbee S.A., Estes P.S., Cziko A.M., Hillebrand J., Luedeman R.A., RA Coller J.M., Johnson N., Howlett I.C., Geng C., Ueda R., Brand A.H., RA Newbury S.F., Wilhelm J.E., Levine R.B., Nakamura A., Parker R., RA Ramaswami M.; RT "Staufen- and FMRP-containing neuronal RNPs are structurally and RT functionally related to somatic P bodies."; RL Neuron 52:997-1009(2006). RN [10] RP INTERACTION WITH CRICKET PARALYSIS VIRUS PROTEIN 1A (MICROBIAL INFECTION). RX PubMed=20400949; DOI=10.1038/nsmb.1810; RA Nayak A., Berry B., Tassetto M., Kunitomi M., Acevedo A., Deng C., RA Krutchinsky A., Gross J., Antoniewski C., Andino R.; RT "Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral RT defense in Drosophila."; RL Nat. Struct. Mol. Biol. 17:547-554(2010). RN [11] RP INTERACTION WITH 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 [12] RP FUNCTION, AND MUTAGENESIS OF VAL-966. RX PubMed=32504809; DOI=10.1016/j.ibmb.2020.103415; RA Lee S., Hong J.S., Lim D.H., Lee Y.S.; RT "Roles for Drosophila cap1 2'-O-ribose methyltransferase in the small RNA RT silencing pathway associated with Argonaute 2."; RL Insect Biochem. Mol. Biol. 123:103415-103415(2020). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 591-726. RX PubMed=14625589; DOI=10.1038/nsb1016; RA Song J.J., Liu J., Tolia N.H., Schneiderman J., Smith S.K., RA Martienssen R.A., Hannon G.J., Joshua-Tor L.; RT "The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding RT motif in RNAi effector complexes."; RL Nat. Struct. Biol. 10:1026-1032(2003). RN [14] RP STRUCTURE BY NMR OF 602-740. RX PubMed=14615801; DOI=10.1038/nature02123; RA Lingel A., Simon B., Izaurralde E., Sattler M.; RT "Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ RT domain."; RL Nature 426:465-469(2003). RN [15] RP STRUCTURE BY NMR OF 605-720. RX PubMed=15156196; DOI=10.1038/nsmb777; RA Lingel A., Simon B., Izaurralde E., Sattler M.; RT "Nucleic acid 3'-end recognition by the Argonaute2 PAZ domain."; RL Nat. Struct. Mol. Biol. 11:576-577(2004). CC -!- FUNCTION: Essential for RNA interference (RNAi); double-stranded RNA CC induces potent and specific gene silencing (PubMed:11498593, CC PubMed:12368261, PubMed:14508492, PubMed:32504809). RNAi is mediated by CC the RNA-induced silencing complex (RISC), a sequence-specific, CC multicomponent nuclease that destroys or silences messenger RNAs CC homologous to the silencing trigger (PubMed:11498593, PubMed:12368261, CC PubMed:14508492). {ECO:0000269|PubMed:11498593, CC ECO:0000269|PubMed:12368261, ECO:0000269|PubMed:14508492, CC ECO:0000269|PubMed:32504809}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- SUBUNIT: Interacts with Fmr1, Dcr-1 and vig to form the RNA-induced CC silencing complex (RISC), a ribonucleoprotein (RNP) complex involved in CC translation regulation, other components of the complex are RpL5, RpL11 CC and Rm62 (PubMed:11498593, PubMed:14508492, PubMed:12368261). As part CC of the RISC complex, interacts with Tudor-SN (PubMed:14508492). CC Interacts with Taf11 (PubMed:26257286). {ECO:0000269|PubMed:11498593, CC ECO:0000269|PubMed:12368261, ECO:0000269|PubMed:14508492, CC ECO:0000269|PubMed:26257286}. CC -!- SUBUNIT: (Microbial infection) Interacts with cricket paralysis virus CC protein 1A; this interaction may block the RISC activity. CC {ECO:0000269|PubMed:20400949}. CC -!- INTERACTION: CC Q9VUQ5; Q9NFU0: Fmr1; NbExp=4; IntAct=EBI-442476, EBI-422631; CC Q9VUQ5; Q9IJX4: ORF1; Xeno; NbExp=3; IntAct=EBI-442476, EBI-15848754; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26257286}. Cytoplasm, CC Cytoplasmic ribonucleoprotein granule {ECO:0000269|PubMed:17178403, CC ECO:0000269|PubMed:26257286}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=B; CC IsoId=Q9VUQ5-1; Sequence=Displayed; CC Name=C; CC IsoId=Q9VUQ5-2; Sequence=VSP_050781; CC -!- DOMAIN: PAZ domain provides a major contribution for nucleic acid CC recognition. PAZ binds oligonucleotides of different lengths and has a CC strong preference for single-stranded nucleic acids (ssRNA or SSDNA) or CC RNA duplexes with single-stranded 3' overhangs. Can bind the CC characteristic two-base 3' overhangs of siRNAs, indicating that it may CC contribute to the specific and productive incorporation of siRNAs and CC miRNAs into the RNAi pathway. CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAM11104.1; 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; AE014296; AAF49619.2; -; Genomic_DNA. DR EMBL; AE014296; AAF49620.2; -; Genomic_DNA. DR EMBL; BT003546; AAO39550.1; -; mRNA. DR EMBL; BT099682; ACV44468.1; -; mRNA. DR EMBL; DQ228766; ABB54719.1; -; Genomic_DNA. DR EMBL; DQ228767; ABB54720.1; -; Genomic_DNA. DR EMBL; DQ228768; ABB54721.1; -; Genomic_DNA. DR EMBL; DQ228769; ABB54722.1; -; Genomic_DNA. DR EMBL; DQ228770; ABB54723.1; -; Genomic_DNA. DR EMBL; DQ228771; ABB54724.1; -; Genomic_DNA. DR EMBL; DQ228772; ABB54725.1; -; Genomic_DNA. DR EMBL; DQ228773; ABB54726.1; -; Genomic_DNA. DR EMBL; AY094751; AAM11104.1; ALT_INIT; mRNA. DR RefSeq; NP_648775.1; NM_140518.3. [Q9VUQ5-1] DR RefSeq; NP_730054.1; NM_168626.3. [Q9VUQ5-2] DR PDB; 1R6Z; X-ray; 2.80 A; A/P/Z=589-726. DR PDB; 1T2R; NMR; -; A=602-720. DR PDB; 1T2S; NMR; -; A=602-720. DR PDB; 1VYN; NMR; -; A=602-740. DR PDB; 3MJ0; X-ray; 2.31 A; A=601-723. DR PDBsum; 1R6Z; -. DR PDBsum; 1T2R; -. DR PDBsum; 1T2S; -. DR PDBsum; 1VYN; -. DR PDBsum; 3MJ0; -. DR AlphaFoldDB; Q9VUQ5; -. DR BMRB; Q9VUQ5; -. DR SMR; Q9VUQ5; -. DR BioGRID; 65002; 71. DR ComplexPortal; CPX-2730; siRNA RISC-loading complex, R2D2 variant. DR ComplexPortal; CPX-2732; siRNA RISC-loading complex, loqs variant. DR DIP; DIP-41570N; -. DR IntAct; Q9VUQ5; 32. DR MINT; Q9VUQ5; -. DR STRING; 7227.FBpp0075313; -. DR PaxDb; 7227-FBpp0075313; -. DR ABCD; Q9VUQ5; 1 sequenced antibody. DR EnsemblMetazoa; FBtr0075559; FBpp0075312; FBgn0087035. [Q9VUQ5-1] DR EnsemblMetazoa; FBtr0075560; FBpp0075313; FBgn0087035. [Q9VUQ5-2] DR GeneID; 39683; -. DR KEGG; dme:Dmel_CG7439; -. DR AGR; FB:FBgn0087035; -. DR CTD; 27161; -. DR FlyBase; FBgn0087035; AGO2. DR VEuPathDB; VectorBase:FBgn0087035; -. DR eggNOG; KOG1041; Eukaryota. DR HOGENOM; CLU_004544_7_1_1; -. DR InParanoid; Q9VUQ5; -. DR OMA; QGPQQTW; -. DR OrthoDB; 3060088at2759; -. DR PhylomeDB; Q9VUQ5; -. DR Reactome; R-DME-203927; MicroRNA (miRNA) biogenesis. DR Reactome; R-DME-426486; Small interfering RNA (siRNA) biogenesis. DR Reactome; R-DME-426496; Post-transcriptional silencing by small RNAs. DR SignaLink; Q9VUQ5; -. DR BioGRID-ORCS; 39683; 1 hit in 1 CRISPR screen. DR EvolutionaryTrace; Q9VUQ5; -. DR GenomeRNAi; 39683; -. DR PRO; PR:Q9VUQ5; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; FBgn0087035; Expressed in eye disc (Drosophila) and 23 other cell types or tissues. DR ExpressionAtlas; Q9VUQ5; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase. DR GO; GO:0005829; C:cytosol; HDA:FlyBase. DR GO; GO:1990124; C:messenger ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0071598; C:neuronal ribonucleoprotein granule; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0016442; C:RISC complex; IDA:UniProtKB. DR GO; GO:0070578; C:RISC-loading complex; IDA:FlyBase. DR GO; GO:0070551; F:endoribonuclease activity, cleaving siRNA-paired mRNA; IDA:FlyBase. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004521; F:RNA endonuclease activity; IDA:FlyBase. DR GO; GO:0016891; F:RNA endonuclease activity, producing 5'-phosphomonoesters; IDA:FlyBase. DR GO; GO:0003727; F:single-stranded RNA binding; IDA:FlyBase. DR GO; GO:0035197; F:siRNA binding; IDA:FlyBase. DR GO; GO:0098586; P:cellular response to virus; IMP:FlyBase. DR GO; GO:0007349; P:cellularization; IMP:FlyBase. DR GO; GO:0051607; P:defense response to virus; IMP:FlyBase. DR GO; GO:0009047; P:dosage compensation by hyperactivation of X chromosome; IGI:FlyBase. DR GO; GO:0033227; P:dsRNA transport; IMP:FlyBase. DR GO; GO:0035195; P:miRNA-mediated post-transcriptional gene silencing; IMP:FlyBase. DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:FlyBase. DR GO; GO:0007279; P:pole cell formation; 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:0007367; P:segment polarity determination; IGI:FlyBase. DR GO; GO:0030422; P:siRNA processing; IDA:UniProtKB. DR GO; GO:0090625; P:siRNA-mediated gene silencing by mRNA destabilization; IDA:FlyBase. DR GO; GO:0141007; P:siRNA-mediated retrotransposon silencing by heterochromatin formation; IMP:FlyBase. DR GO; GO:0035190; P:syncytial nuclear migration; IMP:FlyBase. DR CDD; cd02825; PAZ; 1. DR CDD; cd04657; Piwi_ago-like; 1. DR Gene3D; 3.40.50.2300; -; 1. DR Gene3D; 2.170.260.10; paz domain; 1. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1. DR InterPro; IPR014811; ArgoL1. DR InterPro; IPR032472; ArgoL2. DR InterPro; IPR032473; Argonaute_Mid_dom. DR InterPro; IPR032474; Argonaute_N. DR InterPro; IPR003100; PAZ_dom. DR InterPro; IPR036085; PAZ_dom_sf. DR InterPro; IPR003165; Piwi. DR InterPro; IPR045246; Piwi_ago-like. DR InterPro; IPR012337; RNaseH-like_sf. DR InterPro; IPR036397; RNaseH_sf. DR PANTHER; PTHR22891; EUKARYOTIC TRANSLATION INITIATION FACTOR 2C; 1. DR PANTHER; PTHR22891:SF66; PROTEIN ARGONAUTE-2; 1. DR Pfam; PF08699; ArgoL1; 1. DR Pfam; PF16488; ArgoL2; 1. DR Pfam; PF16487; ArgoMid; 1. DR Pfam; PF16486; ArgoN; 1. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF02171; Piwi; 1. DR SMART; SM01163; DUF1785; 1. DR SMART; SM00950; Piwi; 1. DR SUPFAM; SSF101690; PAZ domain; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS50822; PIWI; 1. DR Genevisible; Q9VUQ5; DM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing; KW Host-virus interaction; Magnesium; Manganese; Metal-binding; Nucleus; KW Reference proteome; RNA-binding; RNA-mediated gene silencing. FT CHAIN 1..1214 FT /note="Protein argonaute-2" FT /id="PRO_0000194071" FT DOMAIN 608..717 FT /note="PAZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142" FT DOMAIN 885..1186 FT /note="Piwi" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00150" FT REGION 1..412 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 681..686 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000255" FT REGION 1075..1076 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000255" FT REGION 1119..1127 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000255" FT REGION 1156..1178 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000255" FT COMPBIAS 14..390 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 965 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000250" FT BINDING 1037 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000250" FT BINDING 1173 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000250" FT VAR_SEQ 1..6 FT /note="MGKKDK -> MHFPITTPE (in isoform C)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_050781" FT VARIANT 714 FT /note="S -> R (in strain: 186)" FT /evidence="ECO:0000269|PubMed:16546082" FT VARIANT 740 FT /note="S -> P (in strain: 130)" FT /evidence="ECO:0000269|PubMed:16546082" FT VARIANT 783 FT /note="S -> N (in strain: 138, 140 and 196)" FT /evidence="ECO:0000269|PubMed:12537569, FT ECO:0000269|PubMed:16546082" FT VARIANT 835 FT /note="T -> A (in strain: 128, 130, 138, 140, 141, 186, 187 FT and 196)" FT /evidence="ECO:0000269|PubMed:12537569, FT ECO:0000269|PubMed:16546082" FT VARIANT 854 FT /note="S -> T (in strain: 128, 130, 138, 140, 141, 186, 187 FT and 196)" FT /evidence="ECO:0000269|PubMed:12537569, FT ECO:0000269|PubMed:16546082" FT VARIANT 866 FT /note="D -> E (in strain: 128, 130, 141, 186 and 187)" FT /evidence="ECO:0000269|PubMed:16546082" FT MUTAGEN 966 FT /note="V->M: Impaired conversion of the pre-RISC complex, FT containing duplex siRNA, to the holo-RISC complex, FT containing single-stranded guide siRNA." FT /evidence="ECO:0000269|PubMed:32504809" FT CONFLICT 201 FT /note="G -> D (in Ref. 3; AAO39550)" FT /evidence="ECO:0000305" FT STRAND 601..603 FT /evidence="ECO:0007829|PDB:3MJ0" FT HELIX 604..611 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 618..621 FT /evidence="ECO:0007829|PDB:1VYN" FT HELIX 623..625 FT /evidence="ECO:0007829|PDB:3MJ0" FT HELIX 627..634 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 638..641 FT /evidence="ECO:0007829|PDB:3MJ0" FT HELIX 645..647 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 652..655 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 658..663 FT /evidence="ECO:0007829|PDB:3MJ0" FT TURN 664..666 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 668..677 FT /evidence="ECO:0007829|PDB:3MJ0" FT HELIX 678..683 FT /evidence="ECO:0007829|PDB:3MJ0" FT TURN 684..686 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 692..698 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 705..708 FT /evidence="ECO:0007829|PDB:1T2R" FT HELIX 710..712 FT /evidence="ECO:0007829|PDB:3MJ0" FT STRAND 713..716 FT /evidence="ECO:0007829|PDB:3MJ0" FT TURN 717..719 FT /evidence="ECO:0007829|PDB:1T2R" SQ SEQUENCE 1214 AA; 136850 MW; 0DC73AF09CC33F73 CRC64; MGKKDKNKKG GQDSAAAPQP QQQQKQQQQR QQQPQQLQQP QQLQQPQQLQ QPQQQQQQQP HQQQQQSSRQ QPSTSSGGSR ASGFQQGGQQ QKSQDAEGWT AQKKQGKQQV QGWTKQGQQG GHQQGRQGQD GGYQQRPPGQ QQGGHQQGRQ GQEGGYQQRP PGQQQGGHQQ GRQGQEGGYQ QRPSGQQQGG HQQGRQGQEG GYQQRPPGQQ QGGHQQGRQG QEGGYQQRPS GQQQGGHQQG RQGQEGGYQQ RPPGQQQGGH QQGRQGQEGG YQQRPPGQQQ GGHEQGRQGQ EGGYQQRPSG QQQGGHQQGR QGQEGGYQQR PSGQQQGGHQ QGRQGQEGGY QQRPSGQQQG GHQQGRQGQE GGYQQRPPGQ QPNQTQSQGQ YQSRGPPQQQ QAAPLPLPPQ PAGSIKRGTI GKPGQVGINY LDLDLSKMPS VAYHYDVKIM PERPKKFYRQ AFEQFRVDQL GGAVLAYDGK ASCYSVDKLP LNSQNPEVTV TDRNGRTLRY TIEIKETGDS TIDLKSLTTY MNDRIFDKPM RAMQCVEVVL ASPCHNKAIR VGRSFFKMSD PNNRHELDDG YEALVGLYQA FMLGDRPFLN VDISHKSFPI SMPMIEYLER FSLKAKINNT TNLDYSRRFL EPFLRGINVV YTPPQSFQSA PRVYRVNGLS RAPASSETFE HDGKKVTIAS YFHSRNYPLK FPQLHCLNVG SSIKSILLPI ELCSIEEGQA LNRKDGATQV ANMIKYAATS TNVRKRKIMN LLQYFQHNLD PTISRFGIRI ANDFIVVSTR VLSPPQVEYH SKRFTMVKNG SWRMDGMKFL EPKPKAHKCA VLYCDPRSGR KMNYTQLNDF GNLIISQGKA VNISLDSDVT YRPFTDDERS LDTIFADLKR SQHDLAIVII PQFRISYDTI KQKAELQHGI LTQCIKQFTV ERKCNNQTIG NILLKINSKL NGINHKIKDD PRLPMMKNTM YIGADVTHPS PDQREIPSVV GVAASHDPYG ASYNMQYRLQ RGALEEIEDM FSITLEHLRV YKEYRNAYPD HIIYYRDGVS DGQFPKIKNE ELRCIKQACD KVGCKPKICC VIVVKRHHTR FFPSGDVTTS NKFNNVDPGT VVDRTIVHPN EMQFFMVSHQ AIQGTAKPTR YNVIENTGNL DIDLLQQLTY NLCHMFPRCN RSVSYPAPAY LAHLVAARGR VYLTGTNRFL DLKKEYAKRT IVPEFMKKNP MYFV //