PIWL2_MOUSE
ID PIWL2_MOUSE Reviewed; 971 AA.
AC Q8CDG1; A6H617; Q3TQE8; Q99MV6; Q9JMB6;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Piwi-like protein 2 {ECO:0000305};
DE EC=3.1.26.- {ECO:0000269|PubMed:22020280, ECO:0000269|PubMed:23706823, ECO:0000269|PubMed:26669262};
GN Name=Piwil2 {ECO:0000312|MGI:MGI:1930036};
GN Synonyms=Mili {ECO:0000303|PubMed:28254886, ECO:0000303|PubMed:28633017};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=11578866; DOI=10.1016/s0925-4773(01)00499-3;
RA Kuramochi-Miyagawa S.K., Kimura T., Yomogida K., Kuroiwa A., Tadokoro Y.,
RA Fujita Y., Sato M., Matsuda Y., Nakano T.;
RT "Two mouse piwi-related genes: miwi and mili.";
RL Mech. Dev. 108:121-133(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 359-971, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=11279525; DOI=10.1038/86927;
RA Wang P.J., McCarrey J.R., Yang F., Page D.C.;
RT "An abundance of X-linked genes expressed in spermatogonia.";
RL Nat. Genet. 27:422-426(2001).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=12906857; DOI=10.1016/s0888-7543(03)00129-0;
RA Sasaki T., Shiohama A., Minoshima S., Shimizu N.;
RT "Identification of eight members of the Argonaute family in the human
RT genome.";
RL Genomics 82:323-330(2003).
RN [7]
RP FUNCTION, INTERACTION WITH DDX4, AND DISRUPTION PHENOTYPE.
RX PubMed=14736746; DOI=10.1242/dev.00973;
RA Kuramochi-Miyagawa S., Kimura T., Ijiri T.W., Isobe T., Asada N.,
RA Fujita Y., Ikawa M., Iwai N., Okabe M., Deng W., Lin H., Matsuda Y.,
RA Nakano T.;
RT "Mili, a mammalian member of piwi family gene, is essential for
RT spermatogenesis.";
RL Development 131:839-849(2004).
RN [8]
RP FUNCTION.
RX PubMed=16261612; DOI=10.1002/mrd.20391;
RA Lee J.H., Engel W., Nayernia K.;
RT "Stem cell protein Piwil2 modulates expression of murine spermatogonial
RT stem cell expressed genes.";
RL Mol. Reprod. Dev. 73:173-179(2006).
RN [9]
RP RNA-BINDING.
RX PubMed=16751777; DOI=10.1038/nature04916;
RA Aravin A., Gaidatzis D., Pfeffer S., Lagos-Quintana M., Landgraf P.,
RA Iovino N., Morris P., Brownstein M.J., Kuramochi-Miyagawa S., Nakano T.,
RA Chien M., Russo J.J., Ju J., Sheridan R., Sander C., Zavolan M., Tuschl T.;
RT "A novel class of small RNAs bind to MILI protein in mouse testes.";
RL Nature 442:203-207(2006).
RN [10]
RP INTERACTION WITH MAEL.
RX PubMed=16787967; DOI=10.1093/hmg/ddl158;
RA Costa Y., Speed R.M., Gautier P., Semple C.A., Maratou K., Turner J.M.A.,
RA Cooke H.J.;
RT "Mouse MAELSTROM: the link between meiotic silencing of unsynapsed
RT chromatin and microRNA pathway?";
RL Hum. Mol. Genet. 15:2324-2334(2006).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17446352; DOI=10.1126/science.1142612;
RA Aravin A.A., Sachidanandam R., Girard A., Fejes-Toth K., Hannon G.J.;
RT "Developmentally regulated piRNA clusters implicate MILI in transposon
RT control.";
RL Science 316:744-747(2007).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18381894; DOI=10.1101/gad.1640708;
RA Kuramochi-Miyagawa S., Watanabe T., Gotoh K., Totoki Y., Toyoda A.,
RA Ikawa M., Asada N., Kojima K., Yamaguchi Y., Ijiri T.W., Hata K., Li E.,
RA Matsuda Y., Kimura T., Okabe M., Sakaki Y., Sasaki H., Nakano T.;
RT "DNA methylation of retrotransposon genes is regulated by Piwi family
RT members MILI and MIWI2 in murine fetal testes.";
RL Genes Dev. 22:908-917(2008).
RN [13]
RP RNA-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=18404146; DOI=10.1038/nature06908;
RA Watanabe T., Totoki Y., Toyoda A., Kaneda M., Kuramochi-Miyagawa S.,
RA Obata Y., Chiba H., Kohara Y., Kono T., Nakano T., Surani M.A., Sakaki Y.,
RA Sasaki H.;
RT "Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in
RT mouse oocytes.";
RL Nature 453:539-543(2008).
RN [14]
RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18922463; DOI=10.1016/j.molcel.2008.09.003;
RA Aravin A.A., Sachidanandam R., Bourc'his D., Schaefer C., Pezic D.,
RA Toth K.F., Bestor T., Hannon G.J.;
RT "A piRNA pathway primed by individual transposons is linked to de novo DNA
RT methylation in mice.";
RL Mol. Cell 31:785-799(2008).
RN [15]
RP INTERACTION WITH TDRD1.
RX PubMed=19345100; DOI=10.1016/j.cub.2009.02.061;
RA Wang J., Saxe J.P., Tanaka T., Chuma S., Lin H.;
RT "Mili interacts with tudor domain-containing protein 1 in regulating
RT spermatogenesis.";
RL Curr. Biol. 19:640-644(2009).
RN [16]
RP METHYLATION AT ARG-74; ARG-95; ARG-100; ARG-163 AND ARG-549, SUBCELLULAR
RP LOCATION, INTERACTION WITH TDRD1; PRMT5 AND WDR77, AND MUTAGENESIS OF
RP ARG-9; ARG-39; ARG-45 AND ARG-74.
RX PubMed=19584108; DOI=10.1101/gad.1814809;
RA Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S.,
RA Girard A., Sachidanandam R., Hannon G.J., Aravin A.A.;
RT "Proteomic analysis of murine Piwi proteins reveals a role for arginine
RT methylation in specifying interaction with Tudor family members.";
RL Genes Dev. 23:1749-1762(2009).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP EIF3A; EIF4E AND EIF4G.
RX PubMed=19114715; DOI=10.1074/jbc.m809104200;
RA Unhavaithaya Y., Hao Y., Beyret E., Yin H., Kuramochi-Miyagawa S.,
RA Nakano T., Lin H.;
RT "MILI, a PIWI-interacting RNA-binding protein, is required for germ Line
RT stem cell self-renewal and appears to positively regulate translation.";
RL J. Biol. Chem. 284:6507-6519(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY, 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 METHYLATION AT ARG-74, SUBCELLULAR LOCATION, AND INTERACTION WITH TDRD1.
RX PubMed=19465913; DOI=10.1038/nsmb.1615;
RA Reuter M., Chuma S., Tanaka T., Franz T., Stark A., Pillai R.S.;
RT "Loss of the Mili-interacting Tudor domain-containing protein-1 activates
RT transposons and alters the Mili-associated small RNA profile.";
RL Nat. Struct. Mol. Biol. 16:639-646(2009).
RN [20]
RP METHYLATION AT ARG-45; ARG-74; ARG-83; ARG-95; ARG-100; ARG-144; ARG-156
RP AND ARG-163, AND INTERACTION WITH TDRKH.
RX PubMed=19918066; DOI=10.1073/pnas.0911640106;
RA Chen C., Jin J., James D.A., Adams-Cioaba M.A., Park J.G., Guo Y.,
RA Tenaglia E., Xu C., Gish G., Min J., Pawson T.;
RT "Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain
RT to arginine methylated Miwi.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20336-20341(2009).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=20439430; DOI=10.1101/gad.1902110;
RA Kuramochi-Miyagawa S., Watanabe T., Gotoh K., Takamatsu K., Chuma S.,
RA Kojima-Kita K., Shiromoto Y., Asada N., Toyoda A., Fujiyama A., Totoki Y.,
RA Shibata T., Kimura T., Nakatsuji N., Noce T., Sasaki H., Nakano T.;
RT "MVH in piRNA processing and gene silencing of retrotransposons.";
RL Genes Dev. 24:887-892(2010).
RN [23]
RP INTERACTION WITH MOV10L1.
RX PubMed=20534472; DOI=10.1073/pnas.1003953107;
RA Zheng K., Xiol J., Reuter M., Eckardt S., Leu N.A., McLaughlin K.J.,
RA Stark A., Sachidanandam R., Pillai R.S., Wang P.J.;
RT "Mouse MOV10L1 associates with Piwi proteins and is an essential component
RT of the Piwi-interacting RNA (piRNA) pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11841-11846(2010).
RN [24]
RP INTERACTION WITH MOV10L1.
RX PubMed=20547853; DOI=10.1073/pnas.1007158107;
RA Frost R.J., Hamra F.K., Richardson J.A., Qi X., Bassel-Duby R., Olson E.N.;
RT "MOV10L1 is necessary for protection of spermatocytes against
RT retrotransposons by Piwi-interacting RNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11847-11852(2010).
RN [25]
RP FUNCTION, AND MUTAGENESIS OF ASP-813.
RX PubMed=22020280; DOI=10.1038/nature10547;
RA De Fazio S., Bartonicek N., Di Giacomo M., Abreu-Goodger C., Sankar A.,
RA Funaya C., Antony C., Moreira P.N., Enright A.J., O'Carroll D.;
RT "The endonuclease activity of Mili fuels piRNA amplification that silences
RT LINE1 elements.";
RL Nature 480:259-263(2011).
RN [26]
RP INTERACTION WITH TDRD12.
RX PubMed=24067652; DOI=10.1073/pnas.1316316110;
RA Pandey R.R., Tokuzawa Y., Yang Z., Hayashi E., Ichisaka T., Kajita S.,
RA Asano Y., Kunieda T., Sachidanandam R., Chuma S., Yamanaka S., Pillai R.S.;
RT "Tudor domain containing 12 (TDRD12) is essential for secondary PIWI
RT interacting RNA biogenesis in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:16492-16497(2013).
RN [27]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-813.
RX PubMed=23706823; DOI=10.1016/j.molcel.2013.04.026;
RA Di Giacomo M., Comazzetto S., Saini H., De Fazio S., Carrieri C.,
RA Morgan M., Vasiliauskaite L., Benes V., Enright A.J., O'Carroll D.;
RT "Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1
RT silencing during adult spermatogenesis.";
RL Mol. Cell 50:601-608(2013).
RN [28]
RP INTERACTION WITH GPAT2.
RX PubMed=23611983; DOI=10.1261/rna.038521.113;
RA Shiromoto Y., Kuramochi-Miyagawa S., Daiba A., Chuma S., Katanaya A.,
RA Katsumata A., Nishimura K., Ohtaka M., Nakanishi M., Nakamura T.,
RA Yoshinaga K., Asada N., Nakamura S., Yasunaga T., Kojima-Kita K., Itou D.,
RA Kimura T., Nakano T.;
RT "GPAT2, a mitochondrial outer membrane protein, in piRNA biogenesis in
RT germline stem cells.";
RL RNA 19:803-810(2013).
RN [29]
RP FUNCTION, AND IDENTIFICATION IN THE PET COMPLEX.
RX PubMed=26669262; DOI=10.1016/j.molcel.2015.11.009;
RA Yang Z., Chen K.M., Pandey R.R., Homolka D., Reuter M., Janeiro B.K.,
RA Sachidanandam R., Fauvarque M.O., McCarthy A.A., Pillai R.S.;
RT "PIWI slicing and EXD1 drive biogenesis of nuclear piRNAs from cytosolic
RT targets of the mouse piRNA pathway.";
RL Mol. Cell 61:138-152(2016).
RN [30]
RP FUNCTION.
RX PubMed=28633017; DOI=10.1016/j.devcel.2017.05.021;
RA Wenda J.M., Homolka D., Yang Z., Spinelli P., Sachidanandam R.,
RA Pandey R.R., Pillai R.S.;
RT "Distinct roles of RNA helicases MVH and TDRD9 in PIWI slicing-triggered
RT mammalian piRNA biogenesis and function.";
RL Dev. Cell 41:623-637(2017).
RN [31]
RP INTERACTION WITH TEX19.1.
RX PubMed=28254886; DOI=10.1242/jcs.188763;
RA Tarabay Y., Achour M., Teletin M., Ye T., Teissandier A., Mark M.,
RA Bourc'his D., Viville S.;
RT "Tex19 paralogs are new members of the piRNA pathway controlling
RT retrotransposon suppression.";
RL J. Cell Sci. 130:1463-1474(2017).
RN [32]
RP FUNCTION, INTERACTION WITH ARNTL; CLOCK AND GSK3B, AND TISSUE SPECIFICITY.
RX PubMed=28903391; DOI=10.18632/oncotarget.18973;
RA Lu Y., Zheng X., Hu W., Bian S., Zhang Z., Tao D., Liu Y., Ma Y.;
RT "Cancer/testis antigen PIWIL2 suppresses circadian rhythms by regulating
RT the stability and activity of BMAL1 and CLOCK.";
RL Oncotarget 8:54913-54924(2017).
RN [33]
RP INTERACTION WITH TEX15, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=32381626; DOI=10.1101/gad.335489.119;
RA Yang F., Lan Y., Pandey R.R., Homolka D., Berger S.L., Pillai R.S.,
RA Bartolomei M.S., Wang P.J.;
RT "TEX15 associates with MILI and silences transposable elements in male germ
RT cells.";
RL Genes Dev. 34:745-750(2020).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 38-50 IN COMPLEX WITH TDRD1,
RP SUBUNIT, AND METHYLATION AT ARG-45 AND ARG-74.
RX PubMed=22996915; DOI=10.1261/rna.034181.112;
RA Mathioudakis N., Palencia A., Kadlec J., Round A., Tripsianes K.,
RA Sattler M., Pillai R.S., Cusack S.;
RT "The multiple Tudor domain-containing protein TDRD1 is a molecular scaffold
RT for mouse Piwi proteins and piRNA biogenesis factors.";
RL RNA 18:2056-2072(2012).
CC -!- FUNCTION: Endoribonuclease that plays a central role during
CC spermatogenesis by repressing transposable elements and preventing
CC their mobilization, which is essential for the germline integrity
CC (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894,
CC PubMed:18922463, PubMed:26669262). Plays an essential role in meiotic
CC differentiation of spermatocytes, germ cell differentiation and in
CC self-renewal of spermatogonial stem cells (PubMed:11578866,
CC PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463,
CC PubMed:26669262). Its presence in oocytes suggests that it may
CC participate in similar functions during oogenesis in females
CC (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894,
CC PubMed:18922463, PubMed:26669262). Acts via the piRNA metabolic
CC process, which mediates the repression of transposable elements during
CC meiosis by forming complexes composed of piRNAs and Piwi proteins and
CC govern the methylation and subsequent repression of transposons
CC (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894,
CC PubMed:18922463, PubMed:26669262). During piRNA biosynthesis, plays a
CC key role in the piRNA amplification loop, also named ping-pong
CC amplification cycle, by acting as a 'slicer-competent' piRNA
CC endoribonuclease that cleaves primary piRNAs, which are then loaded
CC onto 'slicer-incompetent' PIWIL4 (PubMed:22020280, PubMed:23706823,
CC PubMed:26669262). PIWIL2 slicing produces a pre-miRNA intermediate,
CC which is then processed in mature piRNAs, and as well as a 16
CC nucleotide by-product that is degraded (PubMed:28633017). Required for
CC PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs
CC antisense (PubMed:18381894, PubMed:18922463, PubMed:26669262). Besides
CC their function in transposable elements repression, piRNAs are probably
CC involved in other processes during meiosis such as translation
CC regulation (PubMed:19114715). Indirectly modulates expression of genes
CC such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8
CC (PubMed:16261612). Represses circadian rhythms by promoting the
CC stability and activity of core clock components ARNTL/BMAL1 and CLOCK
CC by inhibiting GSK3B-mediated phosphorylation and ubiquitination-
CC dependent degradation of these proteins (PubMed:28903391).
CC {ECO:0000269|PubMed:11578866, ECO:0000269|PubMed:14736746,
CC ECO:0000269|PubMed:16261612, ECO:0000269|PubMed:17446352,
CC ECO:0000269|PubMed:18381894, ECO:0000269|PubMed:18922463,
CC ECO:0000269|PubMed:19114715, ECO:0000269|PubMed:22020280,
CC ECO:0000269|PubMed:23706823, ECO:0000269|PubMed:26669262,
CC ECO:0000269|PubMed:28633017, ECO:0000269|PubMed:28903391}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9JMB7};
CC -!- SUBUNIT: Interacts with DDX4, MAEL, EIF3A, EIF4E, EIF4G, PRMT5 and
CC WDR77. Associates with EIF4E- and EIF4G-containing m7G cap-binding
CC complexes. Interacts (when methylated on arginine residues) with TDRD1
CC and TDRKH/TDRD2. Interacts with TDRD12 (PubMed:24067652). Component of
CC the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs
CC (PubMed:26669262). Interacts with MOV10L1 (PubMed:20534472,
CC PubMed:20547853). Interacts with GPAT2 (PubMed:23611983). Interacts
CC with Tex19.1 and, probably, Tex19.2 (PubMed:28254886). Interacts (via
CC PIWI domain) with ARNTL/BMAL1 and CLOCK (PubMed:28903391). Interacts
CC with GSK3B (PubMed:28903391). Interacts with TEX15 (PubMed:32381626).
CC {ECO:0000269|PubMed:14736746, ECO:0000269|PubMed:16787967,
CC ECO:0000269|PubMed:19114715, ECO:0000269|PubMed:19345100,
CC ECO:0000269|PubMed:19465913, ECO:0000269|PubMed:19584108,
CC ECO:0000269|PubMed:19918066, ECO:0000269|PubMed:20534472,
CC ECO:0000269|PubMed:20547853, ECO:0000269|PubMed:22996915,
CC ECO:0000269|PubMed:23611983, ECO:0000269|PubMed:24067652,
CC ECO:0000269|PubMed:26669262, ECO:0000269|PubMed:28254886,
CC ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:32381626}.
CC -!- INTERACTION:
CC Q8CDG1; Q99MV1: Tdrd1; NbExp=6; IntAct=EBI-8573412, EBI-8573364;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11578866,
CC ECO:0000269|PubMed:18922463, ECO:0000269|PubMed:19114715,
CC ECO:0000269|PubMed:19465913, ECO:0000269|PubMed:19584108,
CC ECO:0000269|PubMed:20439430, ECO:0000269|PubMed:32381626}. Note=Present
CC in chromatoid body. Probable component of the meiotic nuage, also named
CC P granule, a germ-cell-specific organelle required to repress
CC transposon activity during meiosis (PubMed:20439430).
CC {ECO:0000269|PubMed:20439430}.
CC -!- TISSUE SPECIFICITY: Expressed in adult testis, specifically in
CC spermatocytes and in spermatogonia (PubMed:11279525, PubMed:11578866,
CC PubMed:12906857, PubMed:18404146, PubMed:18922463, PubMed:19114715,
CC PubMed:19377467, PubMed:28903391). Only detected in primordial germ
CC cells of both sexes. Widely expressed in tumors. Also present at early
CC stages of oocyte growth. Present in the mitotic spermatogonia
CC (PubMed:23706823). Not detected in the first stages of meiosis
CC (preleptotene and leptotene) (PubMed:23706823). Detected at the late
CC zygotene stage and increases throughout pachytene, declining from this
CC stage onward until expression stops at the early round spermatid stage
CC (at protein level) (PubMed:23706823). {ECO:0000269|PubMed:11279525,
CC ECO:0000269|PubMed:11578866, ECO:0000269|PubMed:12906857,
CC ECO:0000269|PubMed:18404146, ECO:0000269|PubMed:18922463,
CC ECO:0000269|PubMed:19114715, ECO:0000269|PubMed:19377467,
CC ECO:0000269|PubMed:23706823, ECO:0000269|PubMed:28903391}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 12.5 dpc until adult in male
CC gonads. In female gonads, detected since 12.5 dpc, then begins to cease
CC after birth and disappears until the development of adult ovary
CC (PubMed:11578866). Highly expressed in embryonic male germ cells at
CC embryonic day 16.5 and expression decreases by postnatal day 2.5
CC (PubMed:32381626). {ECO:0000269|PubMed:11578866,
CC ECO:0000269|PubMed:32381626}.
CC -!- PTM: Arginine methylation by PRMT5 is required for the interaction with
CC Tudor domain-containing protein TDRD1 and subsequent localization to
CC the meiotic nuage, also named P granule. {ECO:0000269|PubMed:19377467,
CC ECO:0000269|PubMed:19465913, ECO:0000269|PubMed:19584108,
CC ECO:0000269|PubMed:19918066, ECO:0000269|PubMed:22996915}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit blocked spermatogenesis at the early
CC prophase of the first meiosis due to transposable elements
CC derepression, and apoptosis occurs subsequently. Female mice are
CC fertile, while male are sterile. {ECO:0000269|PubMed:14736746,
CC ECO:0000269|PubMed:17446352, ECO:0000269|PubMed:18381894}.
CC -!- SIMILARITY: Belongs to the argonaute family. Piwi subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK31965.1; 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; AB032605; BAA93706.1; -; mRNA.
DR EMBL; AK030116; BAC26791.1; -; mRNA.
DR EMBL; AK163647; BAE37436.1; -; mRNA.
DR EMBL; CH466535; EDL35904.1; -; Genomic_DNA.
DR EMBL; BC138444; AAI38445.1; -; mRNA.
DR EMBL; BC145717; AAI45718.1; -; mRNA.
DR EMBL; AF285586; AAK31965.1; ALT_INIT; mRNA.
DR CCDS; CCDS27252.1; -.
DR RefSeq; NP_067283.1; NM_021308.1.
DR RefSeq; XP_006519392.1; XM_006519329.3.
DR PDB; 4B9W; X-ray; 2.10 A; P/S=38-50.
DR PDBsum; 4B9W; -.
DR AlphaFoldDB; Q8CDG1; -.
DR SMR; Q8CDG1; -.
DR BioGRID; 208309; 4.
DR CORUM; Q8CDG1; -.
DR DIP; DIP-48522N; -.
DR IntAct; Q8CDG1; 4.
DR MINT; Q8CDG1; -.
DR STRING; 10090.ENSMUSP00000047385; -.
DR iPTMnet; Q8CDG1; -.
DR PhosphoSitePlus; Q8CDG1; -.
DR PaxDb; Q8CDG1; -.
DR PRIDE; Q8CDG1; -.
DR ProteomicsDB; 288175; -.
DR Antibodypedia; 22585; 257 antibodies from 34 providers.
DR DNASU; 57746; -.
DR Ensembl; ENSMUST00000048129; ENSMUSP00000047385; ENSMUSG00000033644.
DR GeneID; 57746; -.
DR KEGG; mmu:57746; -.
DR UCSC; uc007unx.1; mouse.
DR CTD; 55124; -.
DR MGI; MGI:1930036; Piwil2.
DR VEuPathDB; HostDB:ENSMUSG00000033644; -.
DR eggNOG; KOG1042; Eukaryota.
DR GeneTree; ENSGT00950000183200; -.
DR HOGENOM; CLU_008813_0_0_1; -.
DR InParanoid; Q8CDG1; -.
DR OMA; CLPFYNV; -.
DR OrthoDB; 220258at2759; -.
DR PhylomeDB; Q8CDG1; -.
DR TreeFam; TF354206; -.
DR BioGRID-ORCS; 57746; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Piwil2; mouse.
DR PRO; PR:Q8CDG1; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8CDG1; protein.
DR Bgee; ENSMUSG00000033644; Expressed in spermatocyte and 81 other tissues.
DR ExpressionAtlas; Q8CDG1; baseline and differential.
DR Genevisible; Q8CDG1; MM.
DR GO; GO:0033391; C:chromatoid body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0097433; C:dense body; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043186; C:P granule; IDA:UniProtKB.
DR GO; GO:0010370; C:perinucleolar chromocenter; IDA:MGI.
DR GO; GO:1990923; C:PET complex; IDA:UniProtKB.
DR GO; GO:0071546; C:pi-body; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0034584; F:piRNA binding; IDA:UniProtKB.
DR GO; GO:1905538; F:polysome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; IMP:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IMP:UniProtKB.
DR GO; GO:0030718; P:germ-line stem cell population maintenance; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; IMP:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IEP:UniProtKB.
DR GO; GO:1990511; P:piRNA biosynthetic process; IDA:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; IDA:UniProtKB.
DR GO; GO:0071442; P:positive regulation of histone H3-K14 acetylation; IMP:CACAO.
DR GO; GO:2000617; P:positive regulation of histone H3-K9 acetylation; IDA:CACAO.
DR GO; GO:0060903; P:positive regulation of meiosis I; IMP:MGI.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0000966; P:RNA 5'-end processing; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR014811; ArgoL1.
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; PF08699; ArgoL1; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 1.
DR SMART; SM01163; DUF1785; 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; Biological rhythms; Cytoplasm; Developmental protein;
KW Differentiation; Endonuclease; Hydrolase; Meiosis; Metal-binding;
KW Methylation; Nuclease; Oogenesis; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing; Spermatogenesis; Translation regulation.
FT CHAIN 1..971
FT /note="Piwi-like protein 2"
FT /id="PRO_0000234570"
FT DOMAIN 386..494
FT /note="PAZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT DOMAIN 666..957
FT /note="Piwi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00150"
FT REGION 102..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 159..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 743
FT /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT ACT_SITE 781
FT /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT ACT_SITE 813
FT /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT ACT_SITE 946
FT /evidence="ECO:0000250|UniProtKB:A8D8P8"
FT MOD_RES 45
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000269|PubMed:19918066,
FT ECO:0000269|PubMed:22996915"
FT MOD_RES 74
FT /note="Omega-N-methylarginine; by PRMT5; alternate"
FT /evidence="ECO:0000269|PubMed:19465913,
FT ECO:0000269|PubMed:19584108, ECO:0000269|PubMed:19918066,
FT ECO:0000269|PubMed:22996915"
FT MOD_RES 74
FT /note="Symmetric dimethylarginine; by PRMT5; alternate"
FT /evidence="ECO:0000269|PubMed:19465913,
FT ECO:0000269|PubMed:19584108, ECO:0000269|PubMed:19918066,
FT ECO:0000269|PubMed:22996915"
FT MOD_RES 83
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:19918066"
FT MOD_RES 83
FT /note="Symmetric dimethylarginine; alternate"
FT /evidence="ECO:0000305|PubMed:19918066"
FT MOD_RES 95
FT /note="Omega-N-methylarginine; by PRMT5; alternate"
FT /evidence="ECO:0000269|PubMed:19584108,
FT ECO:0000269|PubMed:19918066"
FT MOD_RES 95
FT /note="Symmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:19584108,
FT ECO:0000269|PubMed:19918066"
FT MOD_RES 100
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:19584108,
FT ECO:0000269|PubMed:19918066"
FT MOD_RES 100
FT /note="Symmetric dimethylarginine; by PRMT5; alternate"
FT /evidence="ECO:0000269|PubMed:19584108,
FT ECO:0000269|PubMed:19918066"
FT MOD_RES 144
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000305|PubMed:19918066"
FT MOD_RES 156
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000305|PubMed:19918066"
FT MOD_RES 163
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000269|PubMed:19584108,
FT ECO:0000269|PubMed:19918066"
FT MOD_RES 549
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000269|PubMed:19584108"
FT MUTAGEN 9
FT /note="R->K: Abolishes interaction with TDRD1; when
FT associated with K-39; K-45 and K-74."
FT /evidence="ECO:0000269|PubMed:19584108"
FT MUTAGEN 39
FT /note="R->K: Abolishes interaction with TDRD1; when
FT associated with K-9; K-45 and K-74."
FT /evidence="ECO:0000269|PubMed:19584108"
FT MUTAGEN 45
FT /note="R->K: Abolishes interaction with TDRD1; when
FT associated with K-9; K-39 and K-74."
FT /evidence="ECO:0000269|PubMed:19584108"
FT MUTAGEN 74
FT /note="R->K: Abolishes interaction with TDRD1; when
FT associated with K-9; K-39 and K-45."
FT /evidence="ECO:0000269|PubMed:19584108"
FT MUTAGEN 813
FT /note="D->A: In DAH mutant; leads to arrest in meiotic
FT prophase due to a failure of transposon piRNA
FT amplification, resulting in the marked reduction of piRNA-
FT bound within PIWIL4."
FT /evidence="ECO:0000269|PubMed:22020280,
FT ECO:0000269|PubMed:23706823"
FT CONFLICT 517
FT /note="Q -> E (in Ref. 2; BAE37436)"
FT /evidence="ECO:0000305"
FT CONFLICT 542
FT /note="T -> A (in Ref. 2; BAC26791)"
FT /evidence="ECO:0000305"
FT CONFLICT 583
FT /note="D -> G (in Ref. 5; AAK31965)"
FT /evidence="ECO:0000305"
FT CONFLICT 634
FT /note="I -> T (in Ref. 5; AAK31965)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 971 AA; 109488 MW; 01E143C6513310FB CRC64;
MDPVRPLFRG PTPVHPSQCV RMPGCWPQAP RPLEPAWGRA GPAGRGLVFR KPEDSSPPLQ
PVQKDSVGLV SMFRGMGLDT AFRPPSKREV PPLGRGVLGR GLSANMVRKD REEPRSSLPD
PSVLAAGDSK LAEASVGWSR MLGRGSSEVS LLPLGRAASS IGRGMDKPPS AFGLTARDPP
RLPQPPALSP TSLHSADPPP VLTMERKEKE LLVKQGSKGT PQSLGLNLIK IQCHNEAVYQ
YHVTFSPSVE CKSMRFGMLK DHQSVTGNVT AFDGSILYLP VKLQQVVELK SQRKTDDAEI
SIKIQLTKIL EPCSDLCIPF YNVVFRRVMK LLDMKLVGRN FYDPTSAMVL QQHRLQIWPG
YAASIRRTDG GLFLLADVSH KVIRNDSVLD VMHAIYQQNK EHFQDECSKL LVGSIVITRY
NNRTYRIDDV DWNKTPKDSF VMSDGKEITF LEYYSKNYGI TVKEDDQPLL IHRPSERQNN
HGMLLKGEIL LLPELSFMTG IPEKMKKDFR AMKDLTQQIN LSPKQHHGAL ECLLQRISQN
ETASNELTRW GLSLHKDVHK IEGRLLPMER INLRNTSFVT SEDLNWVKEV TRDASILTIP
MHFWALFYPK RAMDQARELV NMLEKIAGPI GMRISPPAWV ELKDDRIETY IRTIQSLLGV
EGKIQMVVCI IMGTRDDLYG AIKKLCCVQS PVPSQVINVR TIGQPTRLRS VAQKILLQMN
CKLGGELWGV DIPLKQLMVI GMDVYHDPSR GMRSVVGFVA SINLTLTKWY SRVVFQMPHQ
EIVDSLKLCL VGSLKKYYEV NHCLPEKIVV YRDGVSDGQL KTVANYEIPQ LQKCFEAFDN
YHPKMVVFVV QKKISTNLYL AAPDHFVTPS PGTVVDHTIT SCEWVDFYLL AHHVRQGCGI
PTHYICVLNT ANLSPDHMQR LTFKLCHMYW NWPGTIRVPA PCKYAHKLAF LSGQILHHEP
AIQLCGNLFF L
