ID PIWI_DROME Reviewed; 843 AA. AC Q9VKM1; C0PTU6; K7WKS7; K7WKT2; K7WQ39; K7WS94; K7XHZ2; L0CPR8; AC L0CPS4; L0CQ04; L0CR36; L0CRH9; L0CRI5; L0CRU0; O96674; O96675; AC Q6NNZ4; Q6NP34; DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 05-DEC-2018, entry version 129. DE RecName: Full=Protein piwi; DE EC=3.1.26.- {ECO:0000250|UniProtKB:A8D8P8}; GN Name=piwi; ORFNames=CG6122; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; OC Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, DEVELOPMENTAL RP STAGE, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RC STRAIN=Canton-S, and Oregon-R; RX PubMed=9851978; DOI=10.1101/gad.12.23.3715; RA Cox D.N., Chao A., Baker J., Chang L., Qiao D., Lin H.; RT "A novel class of evolutionarily conserved genes defined by piwi are RT essential for stem cell self-renewal."; RL Genes Dev. 12:3715-3727(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=3846, 3852, 3854, 3892, 3893, 3894, and 3895; RX PubMed=22997235; DOI=10.1534/genetics.112.145714; RA Lee Y.C., Langley C.H.; RT "Long-term and short-term evolutionary impacts of transposable RT elements on Drosophila."; RL Genetics 192:1411-1432(2012). RN [3] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [4] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., RA Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., RA George R., Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., RA Miranda A., Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., RA Patel S., Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., RA Celniker S.; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.; RL Submitted (MAR-2009) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Fablet M., Akkouche A., Braman V., Vieira C.; RT "Variability in the piRNA pathway induces a variable load of RT transposable elements in wild type strains of Drosophila simulans."; RL Submitted (SEP-2012) to the EMBL/GenBank/DDBJ databases. RN [8] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=9199372; RA Lin H., Spradling A.C.; RT "A novel group of pumilio mutations affects the asymmetric division of RT germline stem cells in the Drosophila ovary."; RL Development 124:2463-2476(1997). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10631171; RA Cox D.N., Chao A., Lin H.; RT "piwi encodes a nucleoplasmic factor whose activity modulates the RT number and division rate of germline stem cells."; RL Development 127:503-514(2000). RN [10] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15817569; DOI=10.1093/nar/gki323; RA Kalmykova A.I., Klenov M.S., Gvozdev V.A.; RT "Argonaute protein PIWI controls mobilization of retrotransposons in RT the Drosophila male germline."; RL Nucleic Acids Res. 33:2052-2059(2005). RN [11] RP FUNCTION, INTERACTION WITH VAS; DCR-1 AND FMR1, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. 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 [12] RP FUNCTION, RNA-BINDING, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=16882972; DOI=10.1101/gad.1454806; RA Saito K., Nishida K.M., Mori T., Kawamura Y., Miyoshi K., Nagami T., RA Siomi H., Siomi M.C.; RT "Specific association of Piwi with rasiRNAs derived from RT retrotransposon and heterochromatic regions in the Drosophila RT genome."; RL Genes Dev. 20:2214-2222(2006). RN [13] RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RX PubMed=17346786; DOI=10.1016/j.cell.2007.01.043; RA Brennecke J., Aravin A.A., Stark A., Dus M., Kellis M., RA Sachidanandam R., Hannon G.J.; RT "Discrete small RNA-generating loci as master regulators of transposon RT activity in Drosophila."; RL Cell 128:1089-1103(2007). RN [14] RP FUNCTION, INTERACTION WITH CBX5, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF VAL-30 AND RP VAL-130. RX PubMed=17875665; DOI=10.1101/gad.1564307; RA Brower-Toland B., Findley S.D., Jiang L., Liu L., Yin H., Dus M., RA Zhou P., Elgin S.C., Lin H.; RT "Drosophila PIWI associates with chromatin and interacts directly with RT HP1a."; RL Genes Dev. 21:2300-2311(2007). RN [15] RP FUNCTION, AND RNA-BINDING. RX PubMed=17952056; DOI=10.1038/nature06263; RA Yin H., Lin H.; RT "An epigenetic activation role of Piwi and a Piwi-associated piRNA in RT Drosophila melanogaster."; RL Nature 450:304-308(2007). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=19395009; DOI=10.1016/j.cell.2009.04.027; RA Li C., Vagin V.V., Lee S., Xu J., Ma S., Xi H., Seitz H., RA Horwich M.D., Syrzycka M., Honda B.M., Kittler E.L., Zapp M.L., RA Klattenhoff C., Schulz N., Theurkauf W.E., Weng Z., Zamore P.D.; RT "Collapse of germline piRNAs in the absence of Argonaute3 reveals RT somatic piRNAs in flies."; RL Cell 137:509-521(2009). RN [17] RP RNA-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-614 AND RP ASP-685. RX PubMed=19812547; DOI=10.1038/nature08501; RA Saito K., Inagaki S., Mituyama T., Kawamura Y., Ono Y., Sakota E., RA Kotani H., Asai K., Siomi H., Siomi M.C.; RT "A regulatory circuit for piwi by the large Maf gene traffic jam in RT Drosophila."; RL Nature 461:1296-1299(2009). RN [18] RP RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP METHYLATION. RX PubMed=19377467; DOI=10.1038/ncb1872; RA Kirino Y., Kim N., de Planell-Saguer M., Khandros E., Chiorean S., RA Klein P.S., Rigoutsos I., Jongens T.A., Mourelatos Z.; RT "Arginine methylation of Piwi proteins catalysed by dPRMT5 is required RT for Ago3 and Aub stability."; RL Nat. Cell Biol. 11:652-658(2009). RN [19] RP FUNCTION, INTERACTION WITH ARMI AND FS(1)YB, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF ARG-54; THR-67 AND 327-TYR-TYR-328. RX PubMed=20966047; DOI=10.1101/gad.1989510; RA Saito K., Ishizu H., Komai M., Kotani H., Kawamura Y., Nishida K.M., RA Siomi H., Siomi M.C.; RT "Roles for the Yb body components Armitage and Yb in primary piRNA RT biogenesis in Drosophila."; RL Genes Dev. 24:2493-2498(2010). RN [20] RP INTERACTION WITH PAPI, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 7-ARG--ARG-9. RX PubMed=21447556; DOI=10.1242/dev.059287; RA Liu L., Qi H., Wang J., Lin H.; RT "PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and RT TRAL in the nuage to silence transposition."; RL Development 138:1863-1873(2011). RN [21] RP INTERACTION WITH VRET. RX PubMed=21831924; DOI=10.1242/dev.069187; RA Zamparini A.L., Davis M.Y., Malone C.D., Vieira E., Zavadil J., RA Sachidanandam R., Hannon G.J., Lehmann R.; RT "Vreteno, a gonad-specific protein, is essential for germline RT development and primary piRNA biogenesis in Drosophila."; RL Development 138:4039-4050(2011). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH HOP RP AND HSP83, AND PHOSPHORYLATION. RX PubMed=21186352; DOI=10.1038/ng.743; RA Gangaraju V.K., Yin H., Weiner M.M., Wang J., Huang X.A., Lin H.; RT "Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic RT variation."; RL Nat. Genet. 43:153-158(2011). RN [23] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22065765; DOI=10.1073/pnas.1106676108; RA Klenov M.S., Sokolova O.A., Yakushev E.Y., Stolyarenko A.D., RA Mikhaleva E.A., Lavrov S.A., Gvozdev V.A.; RT "Separation of stem cell maintenance and transposon silencing RT functions of Piwi protein."; RL Proc. Natl. Acad. Sci. U.S.A. 108:18760-18765(2011). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 4-ASP--PRO-12; RP ASP-614 AND ASP-685. RX PubMed=23159368; DOI=10.1016/j.cell.2012.10.040; RA Sienski G., Donertas D., Brennecke J.; RT "Transcriptional silencing of transposons by Piwi and maelstrom and RT its impact on chromatin state and gene expression."; RL Cell 151:964-980(2012). RN [25] RP FUNCTION. RX PubMed=23434410; DOI=10.1016/j.devcel.2013.01.023; RA Huang X.A., Yin H., Sweeney S., Raha D., Snyder M., Lin H.; RT "A major epigenetic programming mechanism guided by piRNAs."; RL Dev. Cell 24:502-516(2013). RN [26] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 551-TYR--LYS-555. RX PubMed=23392610; DOI=10.1101/gad.209841.112; RA Le Thomas A., Rogers A.K., Webster A., Marinov G.K., Liao S.E., RA Perkins E.M., Hur J.K., Aravin A.A., Toth K.F.; RT "Piwi induces piRNA-guided transcriptional silencing and establishment RT of a repressive chromatin state."; RL Genes Dev. 27:390-399(2013). RN [27] RP FUNCTION. RX PubMed=23392609; DOI=10.1101/gad.209767.112; RA Rozhkov N.V., Hammell M., Hannon G.J.; RT "Multiple roles for Piwi in silencing Drosophila transposons."; RL Genes Dev. 27:400-412(2013). RN [28] RP INTERACTION WITH ARX. RX PubMed=23913921; DOI=10.1101/gad.221515.113; RA Ohtani H., Iwasaki Y.W., Shibuya A., Siomi H., Siomi M.C., Saito K.; RT "DmGTSF1 is necessary for Piwi-piRISC-mediated transcriptional RT transposon silencing in the Drosophila ovary."; RL Genes Dev. 27:1656-1661(2013). RN [29] RP INTERACTION WITH ARX, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23913922; DOI=10.1101/gad.221150.113; RA Doenertas D., Sienski G., Brennecke J.; RT "Drosophila Gtsf1 is an essential component of the Piwi-mediated RT transcriptional silencing complex."; RL Genes Dev. 27:1693-1705(2013). RN [30] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF RP ASP-614 AND ASP-685. RX PubMed=23297219; DOI=10.1073/pnas.1213283110; RA Darricarrere N., Liu N., Watanabe T., Lin H.; RT "Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of RT its slicer activity."; RL Proc. Natl. Acad. Sci. U.S.A. 110:1297-1302(2013). RN [31] RP INTERACTION WITH PANX. RX PubMed=26472911; DOI=10.1126/science.aab0700; RA Yu Y., Gu J., Jin Y., Luo Y., Preall J.B., Ma J., Czech B., RA Hannon G.J.; RT "Panoramix enforces piRNA-dependent cotranscriptional silencing."; RL Science 350:339-342(2015). RN [32] RP INTERACTION WITH PANX. RX PubMed=26494711; DOI=10.1101/gad.271908.115; RA Sienski G., Batki J., Senti K.A., Doenertas D., Tirian L., Meixner K., RA Brennecke J.; RT "Silencio/CG9754 connects the Piwi-piRNA complex to the cellular RT heterochromatin machinery."; RL Genes Dev. 29:2258-2271(2015). RN [33] RP FUNCTION, INTERACTION WITH TUDOR-SN, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=26808625; DOI=10.1371/journal.pgen.1005813; RA Ku H.Y., Gangaraju V.K., Qi H., Liu N., Lin H.; RT "Tudor-SN Interacts with Piwi Antagonistically in Regulating RT Spermatogenesis but Synergistically in Silencing Transposons in RT Drosophila."; RL PLoS Genet. 12:E1005813-E1005813(2016). RN [34] RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 4-12, IDENTIFICATION BY MASS RP SPECTROMETRY, INTERACTION WITH PAPI, METHYLATION AT ARG-7; ARG-9; RP ARG-10 AND ARG-11, AND MUTAGENESIS OF GLN-5; 7-ARG--ARG-11; ARG-7; RP GLY-8; ARG-9; ARG-10; ARG-11; PRO-12; 51-ARG--ARG-54 AND RP 61-ARG--ARG-62. RX PubMed=29531043; DOI=10.1073/pnas.1717116115; RA Zhang Y.H., Liu W.W., Li R.H., Gu J.Q., Wu P., Peng C., Ma J.B., RA Wu L.G., Yu Y., Huang Y.; RT "Structural insights into the sequence-specific recognition of Piwi by RT Drosophila Papi."; RL Proc. Natl. Acad. Sci. U.S.A. 115:3374-3379(2018). CC -!- FUNCTION: Acts via the piwi-interacting RNA (piRNA) metabolic CC process, which mediates the repression of transposable elements CC during meiosis by forming complexes composed of piRNAs and Piwi CC proteins and governs the methylation and subsequent repression of CC transposons (PubMed:26808625, PubMed:15817569, PubMed:17346786). CC Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that CC are generated by a Dicer-independent mechanism and are primarily CC derived from transposons and other repeated sequence elements CC (PubMed:16882972). In ovarian somatic cells, mediates silencing of CC transposable elements at the transcriptional level in a mael- CC dependent manner (PubMed:23159368). Involved in silencing of long CC terminal repeat (LTR) retrotransposons in male germline CC (PubMed:15817569). In testis, regulates spermatogenesis together CC with Tudor-SN (PubMed:26808625). In germ cells, mediates silencing CC at both transcriptional and post-transcriptional levels and is CC involved in the maintenance of populations of primary and CC secondary piRNAs. Piwi-mediated transcriptional silencing is CC accompanied by the formation of His3 'Lys-9' trimethylated CC (H3K9me3) euchromatin and heterochromatin (PubMed:23434410, CC PubMed:23392610). In ovary, associates predominantly with CC antisense piRNAs that contain uridine at their 5' end. Association CC with sense piRNAs is also observed but to a lesser extent. CC Mediates a somatic signaling mechanism required for the CC maintenance of germline stem cells to produce and maintain a CC daughter germline stem cell (PubMed:9851978, PubMed:10631171, CC PubMed:9199372, PubMed:16949822). It is not essential for the CC further differentiation of the committed daughter cell CC (PubMed:9851978). Acts cell autonomously to promote germline stem CC cell division (PubMed:9851978, PubMed:10631171). Its role in stem CC cell maintenance does not seem to require nuclear localization. CC Required maternally for the posterior localization of osk and vas CC and for pole cell formation during oogenesis and early CC embryogenesis (PubMed:16949822). Together with Hop and Hsp83, CC mediates canalization, also known as developmental robustness, CC likely via epigenetic silencing of existing genetic variants and CC suppression of transposon-induced new genetic variation CC (PubMed:21186352). Shows RNA cleavage activity, although is not CC required for any of its known functions (PubMed:9199372, CC PubMed:16882972, PubMed:23297219). {ECO:0000269|PubMed:10631171, CC ECO:0000269|PubMed:15817569, ECO:0000269|PubMed:16882972, CC ECO:0000269|PubMed:16949822, ECO:0000269|PubMed:17346786, CC ECO:0000269|PubMed:17875665, ECO:0000269|PubMed:17952056, CC ECO:0000269|PubMed:20966047, ECO:0000269|PubMed:21186352, CC ECO:0000269|PubMed:22065765, ECO:0000269|PubMed:23159368, CC ECO:0000269|PubMed:23297219, ECO:0000269|PubMed:23392609, CC ECO:0000269|PubMed:23392610, ECO:0000269|PubMed:23434410, CC ECO:0000269|PubMed:26808625, ECO:0000269|PubMed:9199372, CC ECO:0000269|PubMed:9851978}. CC -!- SUBUNIT: Interacts with vas; this interaction is RNA-independent CC (PubMed:16949822). Interacts with Dcr-1 and Fmr1; these CC interactions occur in polar granules (PubMed:16949822). Interacts CC (via N-terminal region) with CBX5 (via chromoshadow domain) CC (PubMed:17875665). Forms a complex with Hsp83 and Hop; probably CC Hop mediates the interaction between piwi and Hsp83 CC (PubMed:21186352). Forms a complex with Yb body components armi CC and fs(1)Yb; this interaction is required for proper piRNA loading CC and nuclear localization of piwi (PubMed:20966047). Interaction of CC Piwi and fs(1)Yb is likely to occur via armi (PubMed:20966047). CC Interacts (via the N-terminal region when unmethylated or CC symmetrically methylated at Arg-10) with papi (via Tudor domain) CC (PubMed:21447556, PubMed:29531043). Interacts with vret CC (PubMed:21831924). Interacts with Panx (PubMed:26472911, CC PubMed:26494711). Interacts with arx (PubMed:23913921, CC PubMed:23913922). Interacts with Tudor-SN (PubMed:26808625). CC {ECO:0000269|PubMed:16949822, ECO:0000269|PubMed:17875665, CC ECO:0000269|PubMed:20966047, ECO:0000269|PubMed:21186352, CC ECO:0000269|PubMed:21447556, ECO:0000269|PubMed:21831924, CC ECO:0000269|PubMed:23913921, ECO:0000269|PubMed:23913922, CC ECO:0000269|PubMed:26472911, ECO:0000269|PubMed:26494711, CC ECO:0000269|PubMed:26808625, ECO:0000269|PubMed:29531043}. CC -!- INTERACTION: CC Q6J5K9:armi; NbExp=4; IntAct=EBI-3406276, EBI-2890374; CC Q9W2H9:Panx; NbExp=2; IntAct=EBI-3406276, EBI-184428; CC Q9VQ91:papi; NbExp=3; IntAct=EBI-3406276, EBI-6915287; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26808625}. CC Nucleus, nucleoplasm {ECO:0000269|PubMed:10631171}. Nucleus CC {ECO:0000269|PubMed:26808625}. Note=Component of polar granules. CC Present in the cytoplasm of the developing oocyte. At the mitotic CC cycle 11 translocates to the nucleus where it remains localized CC throughout germ-cell development and gonadogenesis. Localizes at CC genomic sites enriched for methylated H3K9. CC -!- TISSUE SPECIFICITY: Expressed somatically in ovariole terminal CC filament cells, epithelial sheath cells, cap cells and follicle CC cells (at protein level). Expressed in nurse cells and oocytes in CC developing egg chambers (at protein level) (PubMed:29531043). In CC embryos, accumulates in pole cells (at protein level). In larval CC and adult testis, expressed in a germinal proliferative center at CC the apical tip containing somatic hub cells and mitotically CC dividing germ stem cells (at protein level) (PubMed:26808625). CC {ECO:0000269|PubMed:10631171, ECO:0000269|PubMed:15817569, CC ECO:0000269|PubMed:16882972, ECO:0000269|PubMed:16949822, CC ECO:0000269|PubMed:17346786, ECO:0000269|PubMed:17875665, CC ECO:0000269|PubMed:19377467, ECO:0000269|PubMed:23297219, CC ECO:0000269|PubMed:26808625, ECO:0000269|PubMed:29531043, CC ECO:0000269|PubMed:9199372, ECO:0000269|PubMed:9851978}. CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC Expressed in the germarium, at low levels during oogenesis stages CC 1-6, at a lower level during stages 7-9, strongly at stage 10, CC eventually accumulates in early embryos and later in development CC the expression decreases (at protein level). CC {ECO:0000269|PubMed:16882972, ECO:0000269|PubMed:17346786, CC ECO:0000269|PubMed:17875665, ECO:0000269|PubMed:26808625, CC ECO:0000269|PubMed:9851978}. CC -!- PTM: Symmetrically dimethylated, most likely by csul CC (PubMed:19377467, PubMed:29531043). Methylation at Arg-10 enhances CC binding to papi whereas methylation at Arg-7, Arg-9 or Arg-11 CC reduces binding affinity to papi (PubMed:29531043). CC {ECO:0000269|PubMed:19377467, ECO:0000269|PubMed:29531043}. CC -!- PTM: Phosphorylated on serine and tyrosine residues in an Hsp83- CC dependent manner. {ECO:0000269|PubMed:21186352}. CC -!- DISRUPTION PHENOTYPE: Female mutants show normal ovarian CC development up to third instar larval stage (PubMed:9851978, CC PubMed:9199372, PubMed:26808625). However, adult mutant ovarioles CC contain germaria lacking germline cells and containing two normal CC or abnormal egg chambers as result of the failure of germline stem CC cell maintenance (PubMed:9851978, PubMed:9199372, CC PubMed:26808625). In adult testis, results in deregulation of CC transposon silencing (PubMed:26808625). CC {ECO:0000269|PubMed:26808625, ECO:0000269|PubMed:9199372, CC ECO:0000269|PubMed:9851978}. CC -!- SIMILARITY: Belongs to the argonaute family. Piwi subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAR82763.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=AAR82805.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=ACN43727.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; 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; AF104354; AAD08704.1; -; mRNA. DR EMBL; AF104355; AAD08705.1; -; Genomic_DNA. DR EMBL; KC116149; AGA18878.1; -; Genomic_DNA. DR EMBL; KC116150; AGA18879.1; -; Genomic_DNA. DR EMBL; KC116151; AGA18880.1; -; Genomic_DNA. DR EMBL; KC116152; AGA18881.1; -; Genomic_DNA. DR EMBL; KC116153; AGA18882.1; -; Genomic_DNA. DR EMBL; KC116154; AGA18883.1; -; Genomic_DNA. DR EMBL; KC116155; AGA18884.1; -; Genomic_DNA. DR EMBL; AE014134; AAF53043.1; -; Genomic_DNA. DR EMBL; BT011097; AAR82763.1; ALT_INIT; mRNA. DR EMBL; BT011138; AAR82805.1; ALT_INIT; mRNA. DR EMBL; BT071791; ACN43727.1; ALT_INIT; mRNA. DR EMBL; JX656897; AFX62837.1; -; mRNA. DR EMBL; JX656898; AFX62838.1; -; mRNA. DR EMBL; JX656899; AFX62839.1; -; mRNA. DR EMBL; JX656901; AFX62841.1; -; mRNA. DR EMBL; JX656902; AFX62842.1; -; mRNA. DR RefSeq; NP_001285825.1; NM_001298896.1. DR RefSeq; NP_476875.1; NM_057527.4. DR PDB; 5YGD; X-ray; 1.55 A; D=4-14. DR PDB; 5YGF; X-ray; 1.70 A; D=4-12. DR PDBsum; 5YGD; -. DR PDBsum; 5YGF; -. DR ProteinModelPortal; Q9VKM1; -. DR SMR; Q9VKM1; -. DR BioGrid; 60588; 35. DR DIP; DIP-61694N; -. DR IntAct; Q9VKM1; 25. DR MINT; Q9VKM1; -. DR STRING; 7227.FBpp0079755; -. DR PaxDb; Q9VKM1; -. DR PRIDE; Q9VKM1; -. DR EnsemblMetazoa; FBtr0080166; FBpp0079755; FBgn0004872. DR EnsemblMetazoa; FBtr0340227; FBpp0309202; FBgn0004872. DR GeneID; 34521; -. DR KEGG; dme:Dmel_CG6122; -. DR CTD; 34521; -. DR FlyBase; FBgn0004872; piwi. DR eggNOG; KOG1042; Eukaryota. DR eggNOG; ENOG410XNRH; LUCA. DR InParanoid; Q9VKM1; -. DR KO; K02156; -. DR OMA; LDRWAVI; -. DR OrthoDB; EOG091G020J; -. DR PhylomeDB; Q9VKM1; -. DR GenomeRNAi; 34521; -. DR PRO; PR:Q9VKM1; -. DR Proteomes; UP000000803; Chromosome 2L. DR Bgee; FBgn0004872; Expressed in 9 organ(s), highest expression level in multi-cellular organism. DR ExpressionAtlas; Q9VKM1; baseline and differential. DR Genevisible; Q9VKM1; DM. DR GO; GO:0000785; C:chromatin; IDA:FlyBase. DR GO; GO:0010369; C:chromocenter; IDA:FlyBase. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; HDA:FlyBase. DR GO; GO:0000791; C:euchromatin; IDA:FlyBase. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005700; C:polytene chromosome; IDA:FlyBase. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0031933; C:telomeric heterochromatin; IDA:FlyBase. DR GO; GO:0070725; C:Yb body; IPI:FlyBase. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IDA:FlyBase. DR GO; GO:0006342; P:chromatin silencing; IMP:FlyBase. DR GO; GO:0048132; P:female germ-line stem cell asymmetric division; IMP:UniProtKB. DR GO; GO:0031047; P:gene silencing by RNA; IMP:FlyBase. DR GO; GO:0042078; P:germ-line stem cell division; TAS:FlyBase. DR GO; GO:0030718; P:germ-line stem cell population maintenance; IDA:UniProtKB. DR GO; GO:0007294; P:germarium-derived oocyte fate determination; IMP:FlyBase. DR GO; GO:0070868; P:heterochromatin organization involved in chromatin silencing; IMP:FlyBase. DR GO; GO:0048133; P:male germ-line stem cell asymmetric division; IMP:UniProtKB. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:FlyBase. DR GO; GO:0010529; P:negative regulation of transposition; IMP:FlyBase. DR GO; GO:0000335; P:negative regulation of transposition, DNA-mediated; IMP:FlyBase. DR GO; GO:0048477; P:oogenesis; IMP:UniProtKB. DR GO; GO:0007279; P:pole cell formation; IMP:FlyBase. DR GO; GO:0090309; P:positive regulation of methylation-dependent chromatin silencing; IMP:FlyBase. DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IMP:FlyBase. DR GO; GO:0016441; P:posttranscriptional gene silencing; IMP:FlyBase. DR GO; GO:0016246; P:RNA interference; TAS:FlyBase. DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB. DR Gene3D; 3.30.420.10; -; 1. DR InterPro; IPR003100; PAZ_dom. DR InterPro; IPR036085; PAZ_dom_sf. DR InterPro; IPR003165; Piwi. DR InterPro; IPR012337; RNaseH-like_sf. DR InterPro; IPR036397; RNaseH_sf. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF02171; Piwi; 1. DR SMART; SM00949; PAZ; 1. DR SMART; SM00950; Piwi; 1. DR SUPFAM; SSF101690; SSF101690; 1. DR SUPFAM; SSF53098; SSF53098; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS50822; PIWI; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Cytoplasm; Developmental protein; KW Endonuclease; Hydrolase; Magnesium; Metal-binding; Methylation; KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; RNA-binding; KW RNA-mediated gene silencing. FT CHAIN 1 843 Protein piwi. FT /FTId=PRO_0000194067. FT DOMAIN 262 372 PAZ. {ECO:0000255|PROSITE- FT ProRule:PRU00142}. FT DOMAIN 538 829 Piwi. {ECO:0000255|PROSITE- FT ProRule:PRU00150}. FT REGION 1 257 Interaction with CBX5 and papi. FT {ECO:0000269|PubMed:17875665}. FT MOTIF 1 12 Nuclear localization signal. FT ACT_SITE 614 614 {ECO:0000250|UniProtKB:A8D8P8}. FT ACT_SITE 685 685 {ECO:0000250|UniProtKB:A8D8P8}. FT METAL 589 589 Magnesium. FT {ECO:0000250|UniProtKB:A8D8P8}. FT METAL 843 843 Magnesium; via carboxylate. FT {ECO:0000250|UniProtKB:A8D8P8}. FT MOD_RES 7 7 Symmetric dimethylarginine. FT {ECO:0000269|PubMed:29531043}. FT MOD_RES 9 9 Symmetric dimethylarginine. FT {ECO:0000269|PubMed:29531043}. FT MOD_RES 10 10 Symmetric dimethylarginine. FT {ECO:0000269|PubMed:29531043}. FT MOD_RES 11 11 Symmetric dimethylarginine. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 4 12 Missing: Largely prevents nuclear FT accumulation. Affects repression activity FT of soma- and germline-specific FT transposable elements and fertility. FT {ECO:0000269|PubMed:23159368}. FT MUTAGEN 5 5 Q->A: Reduced binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 7 11 RGRRR->AGAAA: Abolishes binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 7 9 RGR->KGK: Abolishes binding to papi. FT {ECO:0000269|PubMed:21447556}. FT MUTAGEN 7 7 R->A: Large decrease in binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 7 7 R->K: Large decrease in binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 8 8 G->V: Highly significant decrease in FT binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 9 9 R->A: Decreased binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 9 9 R->K: Decreased binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 10 10 R->A: Abolishes binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 10 10 R->K: Abolishes binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 11 11 R->A: Decreased binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 11 11 R->K: Decreased binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 12 12 P->A: No significant effect on binding to FT papi. {ECO:0000269|PubMed:29531043}. FT MUTAGEN 30 30 V->A: Abolishes binding to CBX5; when FT associated with or without A-130. Fails FT to rescue dominant defects in white FT reporter silencing produced by the piwi2 FT mutation. {ECO:0000269|PubMed:17875665}. FT MUTAGEN 51 54 RERR->AEAA: No effect on binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 54 54 R->G: Confers RNAi insensitivity; when FT associated with P-67. FT {ECO:0000269|PubMed:20966047}. FT MUTAGEN 61 62 RR->AA: No effect on binding to papi. FT {ECO:0000269|PubMed:29531043}. FT MUTAGEN 67 67 T->P: Confers RNAi insensitivity; when FT associated with G-54. FT {ECO:0000269|PubMed:20966047}. FT MUTAGEN 130 130 V->A: Abolishes binding to CBX5; when FT associated with A-30. FT {ECO:0000269|PubMed:17875665}. FT MUTAGEN 327 328 YY->AA: Promotes accumulation in the FT cytoplasm. {ECO:0000269|PubMed:20966047}. FT MUTAGEN 551 555 YSSIK->LSSIE: Abolishes binding to FT piRNAs. Reduces localization to the FT nucleus. Does not affect chromatin FT binding. Affects fertility and ovary FT morphology. FT {ECO:0000269|PubMed:23392610}. FT MUTAGEN 614 614 D->A: Does not affect nuclear FT localization, repression activity of FT soma- and germline-specific transposable FT elements, fertility and piRNA loading; FT when associated with or without A-685. FT {ECO:0000269|PubMed:19812547, FT ECO:0000269|PubMed:23159368, FT ECO:0000269|PubMed:23297219}. FT MUTAGEN 685 685 D->A: Does not affect nuclear FT localization, repression activity of FT soma- and germline-specific transposable FT elements, fertility and piRNA loading; FT when associated with or without A-614. FT {ECO:0000269|PubMed:19812547, FT ECO:0000269|PubMed:23159368, FT ECO:0000269|PubMed:23297219}. FT CONFLICT 33 33 F -> S (in Ref. 7; AFX62841/AFX62842). FT {ECO:0000305}. FT CONFLICT 54 54 R -> G (in Ref. 2; AGA18878/AGA18879/ FT AGA18881/AGA18882/AGA18883/AGA18884, 5; FT AAR82805 and 7; AFX62837/AFX62838/ FT AFX62839/AFX62841/AFX62842). FT {ECO:0000305}. FT CONFLICT 67 67 T -> P (in Ref. 1; AAD08704, 2; AGA18878/ FT AGA18879/AGA18880/AGA18881/AGA18882/ FT AGA18883/AGA18884, 5; AAR82805 and 7; FT AFX62837/AFX62838/AFX62839/AFX62841/ FT AFX62842). {ECO:0000305}. FT CONFLICT 80 80 N -> D (in Ref. 2; AGA18882/AGA18883 and FT 5; AAR82805). {ECO:0000305}. FT CONFLICT 84 84 A -> V (in Ref. 1; AAD08704, 2; AGA18878/ FT AGA18879/AGA18880/AGA18881/AGA18882/ FT AGA18883/AGA18884, 5; AAR82805 and 7; FT AFX62837/AFX62838/AFX62839/AFX62841/ FT AFX62842). {ECO:0000305}. FT CONFLICT 122 124 EPS -> VPT (in Ref. 1; AAD08704, 2; FT AGA18880/AGA18881/AGA18882/AGA18883 and FT 5; AAR82805). {ECO:0000305}. FT CONFLICT 182 182 F -> I (in Ref. 2; AGA18884). FT {ECO:0000305}. FT CONFLICT 193 193 F -> L (in Ref. 7; AFX62841). FT {ECO:0000305}. FT CONFLICT 226 226 I -> V (in Ref. 7; AFX62841). FT {ECO:0000305}. FT CONFLICT 240 240 S -> L (in Ref. 7; AFX62842). FT {ECO:0000305}. FT CONFLICT 325 325 V -> L (in Ref. 5; AAR82805). FT {ECO:0000305}. FT CONFLICT 364 364 I -> V (in Ref. 7; AFX62837/AFX62838). FT {ECO:0000305}. FT CONFLICT 496 496 S -> P (in Ref. 7; AFX62837/AFX62838). FT {ECO:0000305}. FT CONFLICT 506 506 L -> P (in Ref. 7; AFX62837/AFX62838). FT {ECO:0000305}. FT CONFLICT 556 556 K -> R (in Ref. 7; AFX62839). FT {ECO:0000305}. FT CONFLICT 576 577 NR -> KPY (in Ref. 1; AAD08705). FT {ECO:0000305}. FT CONFLICT 686 686 G -> R (in Ref. 5; AAR82763). FT {ECO:0000305}. FT CONFLICT 728 728 R -> G (in Ref. 7; AFX62839). FT {ECO:0000305}. FT CONFLICT 818 818 K -> E (in Ref. 7; AFX62842). FT {ECO:0000305}. FT STRAND 7 9 {ECO:0000244|PDB:5YGD}. SQ SEQUENCE 843 AA; 97177 MW; 9B4A95E688E9D9B7 CRC64; MADDQGRGRR RPLNEDDSST SRGSGDGPRV KVFRGSSSGD PRADPRIEAS RERRALEEAP RREGGPTERK PWGDQYDYLN TRPAELVSKK GTDGVPVMLQ TNFFRLKTKP EWRIVHYHVE FEPSIENPRV RMGVLSNHAN LLGSGYLFDG LQLFTTRKFE QEITVLSGKS KLDIEYKISI KFVGFISCAE PRFLQVLNLI LRRSMKGLNL ELVGRNLFDP RAKIEIREFK MELWPGYETS IRQHEKDILL GTEITHKVMR TETIYDIMRR CSHNPARHQD EVRVNVLDLI VLTDYNNRTY RINDVDFGQT PKSTFSCKGR DISFVEYYLT KYNIRIRDHN QPLLISKNRD KALKTNASEL VVLIPELCRV TGLNAEMRSN FQLMRAMSSY TRMNPKQRTD RLRAFNHRLQ NTPESVKVLR DWNMELDKNV TEVQGRIIGQ QNIVFHNGKV PAGENADWQR HFRDQRMLTT PSDGLDRWAV IAPQRNSHEL RTLLDSLYRA ASGMGLRIRS PQEFIIYDDR TGTYVRAMDD CVRSDPKLIL CLVPNDNAER YSSIKKRGYV DRAVPTQVVT LKTTKNRSLM SIATKIAIQL NCKLGYTPWM IELPLSGLMT IGFDIAKSTR DRKRAYGALI ASMDLQQNST YFSTVTECSA FDVLANTLWP MIAKALRQYQ HEHRKLPSRI VFYRDGVSSG SLKQLFEFEV KDIIEKLKTE YARVQLSPPQ LAYIVVTRSM NTRFFLNGQN PPPGTIVDDV ITLPERYDFY LVSQQVRQGT VSPTSYNVLY SSMGLSPEKM QKLTYKMCHL YYNWSGTTRV PAVCQYAKKL ATLVGTNLHS IPQNALEKKF YYL //