ID PIWI_DROME Reviewed; 843 AA. AC Q9VKM1; C0PTU6; K7WKS7; K7WKT2; K7WQ39; K7WS94; K7XHZ2; L0CPR8; L0CPS4; AC L0CQ04; L0CR36; L0CRH9; L0CRI5; L0CRU0; O96674; O96675; Q6NNZ4; Q6NP34; DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 07-APR-2021, entry version 145. 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; Pterygota; OC Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, DEVELOPMENTAL STAGE, RP 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 elements on RT 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., 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 [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., 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M., RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R., RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A., RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S., RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., 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 transposable RT 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 number RT 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 the RT Drosophila male germline."; RL Nucleic Acids Res. 33:2052-2059(2005). RN [11] RP FUNCTION, INTERACTION WITH VAS; DCR-1 AND FMR1, SUBCELLULAR LOCATION, AND RP 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 retrotransposon RT and heterochromatic regions in the Drosophila 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., Sachidanandam R., RA 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 SPECIFICITY, RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF VAL-30 AND 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., Zhou P., RA 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., Horwich M.D., RA Syrzycka M., Honda B.M., Kittler E.L., Zapp M.L., Klattenhoff C., RA Schulz N., Theurkauf W.E., Weng Z., Zamore P.D.; RT "Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic RT piRNAs in flies."; RL Cell 137:509-521(2009). RN [17] RP RNA-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-614 AND 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 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 for RT 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 TRAL in RT 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 development RT and primary piRNA biogenesis in Drosophila."; RL Development 138:4039-4050(2011). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH HOP AND RP 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 functions of RT 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; ASP-614 RP 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 its RT 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 of a RT 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 transposon RT 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 its RT 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., 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 FUNCTION, ASSOCIATION WITH NUCLEAR PORE COMPLEX, INTERACTION WITH ELYS; RP THOC5 AND XMAS-2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=28472469; DOI=10.1093/nar/gkx355; RA Ilyin A.A., Ryazansky S.S., Doronin S.A., Olenkina O.M., Mikhaleva E.A., RA Yakushev E.Y., Abramov Y.A., Belyakin S.N., Ivankin A.V., Pindyurin A.V., RA Gvozdev V.A., Klenov M.S., Shevelyov Y.Y.; RT "Piwi interacts with chromatin at nuclear pores and promiscuously binds RT nuclear transcripts in Drosophila ovarian somatic cells."; RL Nucleic Acids Res. 45:7666-7680(2017). RN [35] RP INTERACTION WITH NUP358, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=29735528; DOI=10.1074/jbc.ac118.003264; RA Parikh R.Y., Lin H., Gangaraju V.K.; RT "A critical role for nucleoporin 358 (Nup358) in transposon silencing and RT piRNA biogenesis in Drosophila."; RL J. Biol. Chem. 293:9140-9147(2018). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, IDENTIFICATION IN A COMPLEX RP WITH NXF2; PANX AND NXT1, AND TISSUE SPECIFICITY. RX PubMed=31368590; DOI=10.15252/embj.2019102870; RA Murano K., Iwasaki Y.W., Ishizu H., Mashiko A., Shibuya A., Kondo S., RA Adachi S., Suzuki S., Saito K., Natsume T., Siomi M.C., Siomi H.; RT "Nuclear RNA export factor variant initiates piRNA-guided co- RT transcriptional silencing."; RL EMBO J. 38:E102870-E102870(2019). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, IDENTIFICATION IN A COMPLEX RP WITH NXF2; PANX AND NXT1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=31384064; DOI=10.1038/s41594-019-0270-6; RA Batki J., Schnabl J., Wang J., Handler D., Andreev V.I., Stieger C.E., RA Novatchkova M., Lampersberger L., Kauneckaite K., Xie W., Mechtler K., RA Patel D.J., Brennecke J.; RT "The nascent RNA binding complex SFiNX licenses piRNA-guided RT heterochromatin formation."; RL Nat. Struct. Mol. Biol. 26:720-731(2019). RN [38] RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 4-12, IDENTIFICATION BY MASS RP SPECTROMETRY, INTERACTION WITH PAPI, METHYLATION AT ARG-7; ARG-9; ARG-10 RP AND ARG-11, AND MUTAGENESIS OF GLN-5; 7-ARG--ARG-11; ARG-7; GLY-8; ARG-9; RP ARG-10; ARG-11; PRO-12; 51-ARG--ARG-54 AND 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., Wu L.G., RA 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 process, CC which mediates the repression of transposable elements during meiosis CC by forming complexes composed of piRNAs and Piwi proteins and governs CC the methylation and subsequent repression of transposons CC (PubMed:26808625, PubMed:15817569, PubMed:17346786). Directly binds CC piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a CC Dicer-independent mechanism and are primarily derived from transposons CC and other repeated sequence elements (PubMed:16882972). In ovarian CC somatic cells, mediates silencing of transposable elements at the CC transcriptional level in a mael-dependent manner (PubMed:23159368, CC PubMed:28472469). Involved in silencing of long terminal repeat (LTR) CC retrotransposons in male germline (PubMed:15817569). In testis, CC regulates spermatogenesis together with Tudor-SN (PubMed:26808625). In CC germ cells, mediates silencing at both transcriptional and post- CC transcriptional levels and is involved in the maintenance of CC populations of primary and secondary piRNAs. Piwi-mediated CC transcriptional silencing is accompanied by the formation of His3 'Lys- CC 9' trimethylated (H3K9me3) euchromatin and heterochromatin CC (PubMed:23434410, PubMed:23392610). In ovary, associates predominantly CC with antisense piRNAs that contain uridine at their 5' end. Association CC with sense piRNAs is also observed but to a lesser extent. Mediates a CC somatic signaling mechanism required for the maintenance of germline CC stem cells to produce and maintain a daughter germline stem cell CC (PubMed:9851978, PubMed:10631171, PubMed:9199372, PubMed:16949822). It CC is not essential for the further differentiation of the committed CC daughter cell (PubMed:9851978). Acts cell autonomously to promote CC germline stem cell division (PubMed:9851978, PubMed:10631171). Its role CC in stem cell maintenance does not seem to require nuclear localization. CC Required maternally for the posterior localization of osk and vas and CC for pole cell formation during oogenesis and early embryogenesis CC (PubMed:16949822). Together with Hop and Hsp83, mediates canalization, CC also known as developmental robustness, likely via epigenetic silencing CC of existing genetic variants and suppression of transposon-induced new CC genetic variation (PubMed:21186352). Shows RNA cleavage activity, CC although is not required for any of its known functions CC (PubMed:9199372, PubMed:16882972, PubMed:23297219). In the ovaries, CC forms a complex with nxf2, Panx and Nxt1 which acts as effectors of CC cotranscriptional transposon silencing (PubMed:31368590, CC PubMed:31384064). {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:28472469, CC ECO:0000269|PubMed:31368590, ECO:0000269|PubMed:31384064, CC ECO:0000269|PubMed:9199372, ECO:0000269|PubMed:9851978}. CC -!- SUBUNIT: In the ovaries, part of a complex composed of at least Panx, CC nxf2, piwi and Nxt1 (PubMed:26472911, PubMed:26494711, PubMed:31368590, CC PubMed:31384064). The complex is knowns as Panx-induced co- CC transcriptional silencing (PICTS) complex, Panx-nxf2-dependent TAP/p15 CC silencing (Pandas complex), SFiNX (silencing factor interacting nuclear CC export variant) or piwi-Panx-nxf2-p15 (PPNP) complex (PubMed:26472911, CC PubMed:26494711, PubMed:31368590, PubMed:31384064). Interacts with vas; CC this interaction is RNA-independent (PubMed:16949822). Interacts with CC Dcr-1 and Fmr1; these interactions occur in polar granules CC (PubMed:16949822). Interacts (via N-terminal region) with CBX5 (via CC chromoshadow domain) (PubMed:17875665). Forms a complex with Hsp83 and CC Hop; probably Hop mediates the interaction between piwi and Hsp83 CC (PubMed:21186352). Forms a complex with Yb body components armi and CC fs(1)Yb; this interaction is required for proper piRNA loading and CC nuclear localization of piwi (PubMed:20966047). Interaction of Piwi and CC fs(1)Yb is likely to occur via armi (PubMed:20966047). Interacts (via CC the N-terminal region when unmethylated or symmetrically methylated at CC Arg-10) with papi (via Tudor domain) (PubMed:21447556, CC PubMed:29531043). Interacts with vret (PubMed:21831924). Interacts with CC Panx (PubMed:26472911, PubMed:26494711). Interacts with arx CC (PubMed:23913921, PubMed:23913922). Interacts with Tudor-SN CC (PubMed:26808625). Interacts with Nup358 (via N-terminus) CC (PubMed:29735528). Associates with the nuclear pore complex via CC interaction with Elys (PubMed:28472469). Interacts with thoc5; the CC interaction might be partly RNA-mediated (PubMed:28472469). Interacts CC with xmas-2 (PubMed:28472469). {ECO:0000269|PubMed:16949822, CC ECO:0000269|PubMed:17875665, ECO:0000269|PubMed:20966047, CC ECO:0000269|PubMed:21186352, ECO:0000269|PubMed:21447556, CC ECO:0000269|PubMed:21831924, ECO:0000269|PubMed:23913921, CC ECO:0000269|PubMed:23913922, ECO:0000269|PubMed:26472911, CC ECO:0000269|PubMed:26494711, ECO:0000269|PubMed:26808625, CC ECO:0000269|PubMed:28472469, ECO:0000269|PubMed:29531043, CC ECO:0000269|PubMed:29735528, ECO:0000269|PubMed:31368590, CC ECO:0000269|PubMed:31384064}. CC -!- INTERACTION: CC Q9VKM1; Q6J5K9: armi; NbExp=4; IntAct=EBI-3406276, EBI-2890374; CC Q9VKM1; Q9W2H9: Panx; NbExp=2; IntAct=EBI-3406276, EBI-184428; CC Q9VKM1; Q9VQ91: papi; NbExp=3; IntAct=EBI-3406276, EBI-6915287; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26808625, CC ECO:0000269|PubMed:29735528}. Nucleus, nucleoplasm CC {ECO:0000269|PubMed:10631171}. Nucleus {ECO:0000269|PubMed:26808625, CC ECO:0000269|PubMed:29735528, ECO:0000269|PubMed:31384064}. Chromosome CC {ECO:0000269|PubMed:28472469}. Note=Component of polar granules. CC Present in the cytoplasm of the developing oocyte. At the mitotic cycle CC 11 translocates to the nucleus where it remains localized throughout CC germ-cell development and gonadogenesis. Localizes at genomic sites CC enriched for methylated H3K9. Interacts with chromatin at the nuclear CC pore complex (PubMed:28472469). {ECO:0000269|PubMed:28472469}. CC -!- TISSUE SPECIFICITY: Expressed in ovaries (at protein level) CC (PubMed:28472469, PubMed:31368590, PubMed:31384064). Expressed CC somatically in ovariole terminal filament cells, epithelial sheath CC cells, cap cells and follicle cells (at protein level). Expressed in CC nurse cells and oocytes in developing egg chambers (at protein level) CC (PubMed:29531043, PubMed:29735528). In embryos, accumulates in pole CC cells (at protein level). In larval and adult testis, expressed in a CC germinal proliferative center at the apical tip containing somatic hub CC cells and mitotically dividing germ stem cells (at protein level) CC (PubMed:26808625). {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:19377467, CC ECO:0000269|PubMed:23297219, ECO:0000269|PubMed:26808625, CC ECO:0000269|PubMed:28472469, ECO:0000269|PubMed:29531043, CC ECO:0000269|PubMed:29735528, ECO:0000269|PubMed:31368590, CC ECO:0000269|PubMed:31384064, ECO:0000269|PubMed:9199372, CC ECO:0000269|PubMed:9851978}. CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC Expressed in the germarium, at low levels during oogenesis stages 1-6, CC at a lower level during stages 7-9, strongly at stage 10, eventually CC accumulates in early embryos and later in development the expression CC decreases (at protein level). {ECO:0000269|PubMed:16882972, CC ECO:0000269|PubMed:17346786, ECO:0000269|PubMed:17875665, CC ECO:0000269|PubMed:26808625, ECO:0000269|PubMed:9851978}. CC -!- PTM: Symmetrically dimethylated, most likely by csul (PubMed:19377467, CC PubMed:29531043). Methylation at Arg-10 enhances binding to papi CC whereas methylation at Arg-7, Arg-9 or Arg-11 reduces binding affinity CC to papi (PubMed:29531043). {ECO:0000269|PubMed:19377467, CC 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 development up CC to third instar larval stage (PubMed:9851978, PubMed:9199372, CC PubMed:26808625). However, adult mutant ovarioles contain germaria CC lacking germline cells and containing two normal or abnormal egg CC chambers as result of the failure of germline stem cell maintenance CC (PubMed:9851978, PubMed:9199372, PubMed:26808625). In adult testis, CC results in deregulation of 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=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAR82805.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=ACN43727.1; Type=Erroneous initiation; Note=Extended 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; 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 PDB; 6KR6; X-ray; 2.90 A; A=34-843. DR PDBsum; 5YGD; -. DR PDBsum; 5YGF; -. DR PDBsum; 6KR6; -. DR SMR; Q9VKM1; -. DR BioGRID; 60588; 56. DR DIP; DIP-61694N; -. DR IntAct; Q9VKM1; 25. DR MINT; Q9VKM1; -. DR STRING; 7227.FBpp0079755; -. DR PaxDb; 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 HOGENOM; CLU_008813_0_0_1; -. DR InParanoid; Q9VKM1; -. DR OMA; RMNPKQR; -. DR OrthoDB; 220258at2759; -. DR PhylomeDB; Q9VKM1; -. DR BioGRID-ORCS; 34521; 0 hits in 3 CRISPR screens. DR GenomeRNAi; 34521; -. DR PRO; PR:Q9VKM1; -. DR Proteomes; UP000000803; Chromosome 2L. DR Bgee; FBgn0004872; Expressed in female gonad and 21 other tissues. 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:0043073; C:germ cell nucleus; IDA:FlyBase. DR GO; GO:0000792; C:heterochromatin; IDA:FlyBase. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0070725; C:Yb body; IPI:FlyBase. DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0034584; F:piRNA binding; IDA:FlyBase. DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB. 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: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: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:1990511; P:piRNA biosynthetic process; IMP:FlyBase. DR GO; GO:0007279; P:pole cell formation; IMP:FlyBase. DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IMP:FlyBase. DR GO; GO:0031453; P:positive regulation of heterochromatin assembly; 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: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; Chromosome; Cytoplasm; Developmental protein; Endonuclease; KW Hydrolase; Magnesium; Metal-binding; Methylation; Nuclease; Nucleus; KW Phosphoprotein; Reference proteome; RNA-binding; KW RNA-mediated gene silencing. FT CHAIN 1..843 FT /note="Protein piwi" FT /id="PRO_0000194067" FT DOMAIN 262..372 FT /note="PAZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142" FT DOMAIN 538..829 FT /note="Piwi" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00150" FT REGION 1..257 FT /note="Interaction with CBX5 and papi" FT /evidence="ECO:0000269|PubMed:17875665" FT MOTIF 1..12 FT /note="Nuclear localization signal" FT ACT_SITE 614 FT /evidence="ECO:0000250|UniProtKB:A8D8P8" FT ACT_SITE 685 FT /evidence="ECO:0000250|UniProtKB:A8D8P8" FT METAL 589 FT /note="Magnesium" FT /evidence="ECO:0000250|UniProtKB:A8D8P8" FT METAL 843 FT /note="Magnesium; via carboxylate" FT /evidence="ECO:0000250|UniProtKB:A8D8P8" FT MOD_RES 7 FT /note="Symmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:29531043" FT MOD_RES 9 FT /note="Symmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:29531043" FT MOD_RES 10 FT /note="Symmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:29531043" FT MOD_RES 11 FT /note="Symmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 4..12 FT /note="Missing: Largely prevents nuclear accumulation. FT Affects repression activity of soma- and germline-specific FT transposable elements and fertility." FT /evidence="ECO:0000269|PubMed:23159368" FT MUTAGEN 5 FT /note="Q->A: Reduced binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 7..11 FT /note="RGRRR->AGAAA: Abolishes binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 7..9 FT /note="RGR->KGK: Abolishes binding to papi." FT /evidence="ECO:0000269|PubMed:21447556" FT MUTAGEN 7 FT /note="R->A: Large decrease in binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 7 FT /note="R->K: Large decrease in binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 8 FT /note="G->V: Highly significant decrease in binding to FT papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 9 FT /note="R->A: Decreased binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 9 FT /note="R->K: Decreased binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 10 FT /note="R->A: Abolishes binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 10 FT /note="R->K: Abolishes binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 11 FT /note="R->A: Decreased binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 11 FT /note="R->K: Decreased binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 12 FT /note="P->A: No significant effect on binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 30 FT /note="V->A: Abolishes binding to CBX5; when associated FT with or without A-130. Fails to rescue dominant defects in FT white reporter silencing produced by the piwi2 mutation." FT /evidence="ECO:0000269|PubMed:17875665" FT MUTAGEN 51..54 FT /note="RERR->AEAA: No effect on binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 54 FT /note="R->G: Confers RNAi insensitivity; when associated FT with P-67." FT /evidence="ECO:0000269|PubMed:20966047" FT MUTAGEN 61..62 FT /note="RR->AA: No effect on binding to papi." FT /evidence="ECO:0000269|PubMed:29531043" FT MUTAGEN 67 FT /note="T->P: Confers RNAi insensitivity; when associated FT with G-54." FT /evidence="ECO:0000269|PubMed:20966047" FT MUTAGEN 130 FT /note="V->A: Abolishes binding to CBX5; when associated FT with A-30." FT /evidence="ECO:0000269|PubMed:17875665" FT MUTAGEN 327..328 FT /note="YY->AA: Promotes accumulation in the cytoplasm." FT /evidence="ECO:0000269|PubMed:20966047" FT MUTAGEN 551..555 FT /note="YSSIK->LSSIE: Abolishes binding to piRNAs. Reduces FT localization to the nucleus. Does not affect chromatin FT binding. Affects fertility and ovary morphology." FT /evidence="ECO:0000269|PubMed:23392610" FT MUTAGEN 614 FT /note="D->A: Does not affect nuclear localization, FT repression activity of soma- and germline-specific FT transposable elements, fertility and piRNA loading; when FT associated with or without A-685." FT /evidence="ECO:0000269|PubMed:19812547, FT ECO:0000269|PubMed:23159368, ECO:0000269|PubMed:23297219" FT MUTAGEN 685 FT /note="D->A: Does not affect nuclear localization, FT repression activity of soma- and germline-specific FT transposable elements, fertility and piRNA loading; when FT associated with or without A-614." FT /evidence="ECO:0000269|PubMed:19812547, FT ECO:0000269|PubMed:23159368, ECO:0000269|PubMed:23297219" FT CONFLICT 33 FT /note="F -> S (in Ref. 7; AFX62841/AFX62842)" FT /evidence="ECO:0000305" FT CONFLICT 54 FT /note="R -> G (in Ref. 2; AGA18878/AGA18879/AGA18881/ FT AGA18882/AGA18883/AGA18884, 5; AAR82805 and 7; AFX62837/ FT AFX62838/AFX62839/AFX62841/AFX62842)" FT /evidence="ECO:0000305" FT CONFLICT 67 FT /note="T -> P (in Ref. 1; AAD08704, 2; AGA18878/AGA18879/ FT AGA18880/AGA18881/AGA18882/AGA18883/AGA18884, 5; AAR82805 FT and 7; AFX62837/AFX62838/AFX62839/AFX62841/AFX62842)" FT /evidence="ECO:0000305" FT CONFLICT 80 FT /note="N -> D (in Ref. 2; AGA18882/AGA18883 and 5; FT AAR82805)" FT /evidence="ECO:0000305" FT CONFLICT 84 FT /note="A -> V (in Ref. 1; AAD08704, 2; AGA18878/AGA18879/ FT AGA18880/AGA18881/AGA18882/AGA18883/AGA18884, 5; AAR82805 FT and 7; AFX62837/AFX62838/AFX62839/AFX62841/AFX62842)" FT /evidence="ECO:0000305" FT CONFLICT 122..124 FT /note="EPS -> VPT (in Ref. 1; AAD08704, 2; AGA18880/ FT AGA18881/AGA18882/AGA18883 and 5; AAR82805)" FT /evidence="ECO:0000305" FT CONFLICT 182 FT /note="F -> I (in Ref. 2; AGA18884)" FT /evidence="ECO:0000305" FT CONFLICT 193 FT /note="F -> L (in Ref. 7; AFX62841)" FT /evidence="ECO:0000305" FT CONFLICT 226 FT /note="I -> V (in Ref. 7; AFX62841)" FT /evidence="ECO:0000305" FT CONFLICT 240 FT /note="S -> L (in Ref. 7; AFX62842)" FT /evidence="ECO:0000305" FT CONFLICT 325 FT /note="V -> L (in Ref. 5; AAR82805)" FT /evidence="ECO:0000305" FT CONFLICT 364 FT /note="I -> V (in Ref. 7; AFX62837/AFX62838)" FT /evidence="ECO:0000305" FT CONFLICT 496 FT /note="S -> P (in Ref. 7; AFX62837/AFX62838)" FT /evidence="ECO:0000305" FT CONFLICT 506 FT /note="L -> P (in Ref. 7; AFX62837/AFX62838)" FT /evidence="ECO:0000305" FT CONFLICT 556 FT /note="K -> R (in Ref. 7; AFX62839)" FT /evidence="ECO:0000305" FT CONFLICT 576..577 FT /note="NR -> KPY (in Ref. 1; AAD08705)" FT /evidence="ECO:0000305" FT CONFLICT 686 FT /note="G -> R (in Ref. 5; AAR82763)" FT /evidence="ECO:0000305" FT CONFLICT 728 FT /note="R -> G (in Ref. 7; AFX62839)" FT /evidence="ECO:0000305" FT CONFLICT 818 FT /note="K -> E (in Ref. 7; AFX62842)" FT /evidence="ECO:0000305" FT STRAND 7..9 FT /evidence="ECO:0007744|PDB:5YGD" FT STRAND 94..107 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 115..123 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 128..136 FT /evidence="ECO:0007744|PDB:6KR6" FT TURN 139..142 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 150..156 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 160..168 FT /evidence="ECO:0007744|PDB:6KR6" FT TURN 170..172 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 175..185 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 191..205 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 206..208 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 211..213 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 216..218 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 220..222 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 224..226 FT /evidence="ECO:0007744|PDB:6KR6" FT TURN 227..230 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 231..243 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 248..260 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 264..271 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 281..286 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 290..293 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 299..301 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 304..306 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 314..316 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 321..323 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 324..331 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 343..345 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 365..367 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 381..391 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 395..411 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 413..421 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 432..438 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 442..444 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 449..451 FT /evidence="ECO:0007744|PDB:6KR6" FT TURN 453..456 FT /evidence="ECO:0007744|PDB:6KR6" FT TURN 459..461 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 479..483 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 484..486 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 487..504 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 512..518 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 521..532 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 539..545 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 548..559 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 566..570 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 571..574 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 579..593 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 606..617 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 625..632 FT /evidence="ECO:0007744|PDB:6KR6" FT TURN 634..637 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 641..647 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 658..673 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 678..685 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 692..713 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 720..728 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 734..736 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 745..747 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 749..752 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 754..756 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 758..762 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 767..769 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 774..781 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 787..797 FT /evidence="ECO:0007744|PDB:6KR6" FT STRAND 804..806 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 812..826 FT /evidence="ECO:0007744|PDB:6KR6" FT HELIX 834..836 FT /evidence="ECO:0007744|PDB:6KR6" 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 //