AGO2_HUMAN
ID AGO2_HUMAN Reviewed; 859 AA.
AC Q9UKV8; Q8TCZ5; Q8WV58; Q96ID1;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Protein argonaute-2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=Argonaute2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=hAgo2;
DE EC=3.1.26.n2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE AltName: Full=Argonaute RISC catalytic component 2;
DE AltName: Full=Eukaryotic translation initiation factor 2C 2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=eIF-2C 2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=eIF2C 2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE AltName: Full=PAZ Piwi domain protein;
DE Short=PPD;
DE AltName: Full=Protein slicer {ECO:0000255|HAMAP-Rule:MF_03031};
GN Name=AGO2; Synonyms=EIF2C2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 239-859 (ISOFORM 1).
RC TISSUE=Brain, and Eye;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 47-859 (ISOFORM 1).
RX PubMed=11914277; DOI=10.1101/gad.974702;
RA Mourelatos Z., Dostie J., Paushkin S., Sharma A., Charroux B., Abel L.,
RA Rappsilber J., Mann M., Dreyfuss G.;
RT "miRNPs: a novel class of ribonucleoproteins containing numerous
RT microRNAs.";
RL Genes Dev. 16:720-728(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 275-859 (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 483-859 (ISOFORM 1).
RX PubMed=10534406; DOI=10.1006/geno.1999.5951;
RA Koesters R., Adams V., Betts D., Moos R., Schmid M., Siermann A.,
RA Hassam S., Weitz S., Lichter P., Heitz P.U., von Knebel Doeberitz M.,
RA Briner J.;
RT "Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic
RT organization, localization to chromosomal bands 1p34-p35, and expression.";
RL Genomics 61:210-218(1999).
RN [6]
RP INTERACTION WITH SND1.
RX PubMed=14508492; DOI=10.1038/nature01956;
RA Caudy A.A., Ketting R.F., Hammond S.M., Denli A.M., Bathoorn A.M.,
RA Tops B.B., Silva J.M., Myers M.M., Hannon G.J., Plasterk R.H.;
RT "A micrococcal nuclease homologue in RNAi effector complexes.";
RL Nature 425:411-414(2003).
RN [7]
RP INTERACTION WITH DICER1.
RX PubMed=14749716; DOI=10.1038/sj.embor.7400070;
RA Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C.;
RT "Characterization of the interactions between mammalian PAZ PIWI domain
RT proteins and Dicer.";
RL EMBO Rep. 5:189-194(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15105377; DOI=10.1101/gad.1187904;
RA Martinez J., Tuschl T.;
RT "RISC is a 5' phosphomonoester-producing RNA endonuclease.";
RL Genes Dev. 18:975-980(2004).
RN [9]
RP FUNCTION.
RX PubMed=15260970; DOI=10.1016/j.molcel.2004.07.007;
RA Meister G., Landthaler M., Patkaniowska A., Dorsett Y., Teng G., Tuschl T.;
RT "Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.";
RL Mol. Cell 15:185-197(2004).
RN [10]
RP INTERACTION WITH FMR1.
RX PubMed=14703574; DOI=10.1038/nn1174;
RA Jin P., Zarnescu D.C., Ceman S., Nakamoto M., Mowrey J., Jongens T.A.,
RA Nelson D.L., Moses K., Warren S.T.;
RT "Biochemical and genetic interaction between the fragile X mental
RT retardation protein and the microRNA pathway.";
RL Nat. Neurosci. 7:113-117(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH GEMIN4.
RX PubMed=15337849; DOI=10.1261/rna.7131604;
RA Pillai R.S., Artus C.G., Filipowicz W.;
RT "Tethering of human Ago proteins to mRNA mimics the miRNA-mediated
RT repression of protein synthesis.";
RL RNA 10:1518-1525(2004).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, MUTAGENESIS OF LEU-140; ASP-597; GLN-633;
RP HIS-634; ASP-669; HIS-682; PHE-704 AND THR-744, AND COFACTOR.
RX PubMed=15284456; DOI=10.1126/science.1102513;
RA Liu J., Carmell M.A., Rivas F.V., Marsden C.G., Thomson J.M., Song J.-J.,
RA Hammond S.M., Joshua-Tor L., Hannon G.J.;
RT "Argonaute2 is the catalytic engine of mammalian RNAi.";
RL Science 305:1437-1441(2004).
RN [13]
RP INTERACTION WITH ZFP36.
RX PubMed=15766526; DOI=10.1016/j.cell.2004.12.038;
RA Jing Q., Huang S., Guth S., Zarubin T., Motoyama A., Chen J., Di Padova F.,
RA Lin S.C., Gram H., Han J.;
RT "Involvement of microRNA in AU-rich element-mediated mRNA instability.";
RL Cell 120:623-634(2005).
RN [14]
RP FUNCTION, AND INTERACTION WITH DICER1 AND TARBP2.
RX PubMed=16271387; DOI=10.1016/j.cell.2005.10.022;
RA Gregory R.I., Chendrimada T.P., Cooch N., Shiekhattar R.;
RT "Human RISC couples microRNA biogenesis and posttranscriptional gene
RT silencing.";
RL Cell 123:631-640(2005).
RN [15]
RP FUNCTION, INTERACTION WITH DDX20; DICER1; GEMIN4; MOV10; PRMT5 AND TNRC6B,
RP AND SUBCELLULAR LOCATION.
RX PubMed=16289642; DOI=10.1016/j.cub.2005.10.048;
RA Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R.,
RA Tuschl T.;
RT "Identification of novel argonaute-associated proteins.";
RL Curr. Biol. 15:2149-2155(2005).
RN [16]
RP FUNCTION.
RX PubMed=16142218; DOI=10.1038/sj.embor.7400509;
RA Haase A.D., Jaskiewicz L., Zhang H., Laine S., Sack R., Gatignol A.,
RA Filipowicz W.;
RT "TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts
RT with Dicer and functions in RNA silencing.";
RL EMBO Rep. 6:961-967(2005).
RN [17]
RP FUNCTION, INTERACTION WITH DICER1 AND TARBP2, AND MUTAGENESIS OF ASP-669.
RX PubMed=16357216; DOI=10.1101/gad.1384005;
RA Maniataki E., Mourelatos Z.;
RT "A human, ATP-independent, RISC assembly machine fueled by pre-miRNA.";
RL Genes Dev. 19:2979-2990(2005).
RN [18]
RP MUTAGENESIS OF LYS-533; GLN-545 AND LYS-570.
RX PubMed=15800629; DOI=10.1038/nature03514;
RA Ma J.-B., Yuan Y.-R., Meister G., Pei Y., Tuschl T., Patel D.J.;
RT "Structural basis for 5'-end-specific recognition of guide RNA by the A.
RT fulgidus Piwi protein.";
RL Nature 434:666-670(2005).
RN [19]
RP INTERACTION WITH DICER1 AND TARBP2.
RX PubMed=15973356; DOI=10.1038/nature03868;
RA Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N.,
RA Nishikura K., Shiekhattar R.;
RT "TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene
RT silencing.";
RL Nature 436:740-744(2005).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=15908945; DOI=10.1038/ncb1265;
RA Sen G.L., Blau H.M.;
RT "Argonaute 2/RISC resides in sites of mammalian mRNA decay known as
RT cytoplasmic bodies.";
RL Nat. Cell Biol. 7:633-636(2005).
RN [21]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ASP-597;
RP ASP-669; GLU-673; GLU-683 AND HIS-807.
RX PubMed=15800637; DOI=10.1038/nsmb918;
RA Rivas F.V., Tolia N.H., Song J.-J., Aragon J.P., Liu J., Hannon G.J.,
RA Joshua-Tor L.;
RT "Purified Argonaute2 and an siRNA form recombinant human RISC.";
RL Nat. Struct. Mol. Biol. 12:340-349(2005).
RN [22]
RP FUNCTION, INTERACTION WITH DCP1A AND XRN1, AND SUBCELLULAR LOCATION.
RX PubMed=16081698; DOI=10.1126/science.1115079;
RA Pillai R.S., Bhattacharyya S.N., Artus C.G., Zoller T., Cougot N.,
RA Basyuk E., Bertrand E., Filipowicz W.;
RT "Inhibition of translational initiation by Let-7 MicroRNA in human cells.";
RL Science 309:1573-1576(2005).
RN [23]
RP FUNCTION.
RX PubMed=16936728; DOI=10.1038/nsmb1140;
RA Janowski B.A., Huffman K.E., Schwartz J.C., Ram R., Nordsell R.,
RA Shames D.S., Minna J.D., Corey D.R.;
RT "Involvement of AGO1 and AGO2 in mammalian transcriptional silencing.";
RL Nat. Struct. Mol. Biol. 13:787-792(2006).
RN [24]
RP FUNCTION, INTERACTION WITH DDX6 AND AGO1, AND SUBCELLULAR LOCATION.
RX PubMed=16756390; DOI=10.1371/journal.pbio.0040210;
RA Chu C.-Y., Rana T.M.;
RT "Translation repression in human cells by microRNA-induced gene silencing
RT requires RCK/p54.";
RL PLoS Biol. 4:E210-E210(2006).
RN [25]
RP INTERACTION WITH APOBEC3G.
RX PubMed=16699599; DOI=10.1371/journal.ppat.0020041;
RA Wichroski M.J., Robb G.B., Rana T.M.;
RT "Human retroviral host restriction factors APOBEC3G and APOBEC3F localize
RT to mRNA processing bodies.";
RL PLoS Pathog. 2:E41-E41(2006).
RN [26]
RP FUNCTION, INTERACTION WITH FXR1, AND SUBCELLULAR LOCATION.
RX PubMed=17382880; DOI=10.1016/j.cell.2007.01.038;
RA Vasudevan S., Steitz J.A.;
RT "AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute
RT 2.";
RL Cell 128:1105-1118(2007).
RN [27]
RP FUNCTION, AND MUTAGENESIS OF PHE-470 AND PHE-505.
RX PubMed=17524464; DOI=10.1016/j.cell.2007.05.016;
RA Kiriakidou M., Tan G.S., Lamprinaki S., De Planell-Saguer M., Nelson P.T.,
RA Mourelatos Z.;
RT "An mRNA m7G cap binding-like motif within human Ago2 represses
RT translation.";
RL Cell 129:1141-1151(2007).
RN [28]
RP FUNCTION, ASSOCIATION WITH POLYSOMES AND MNRP, AND INTERACTION WITH DDB1;
RP DDX5; DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1;
RP RBM4; SART3; UPF1 AND YBX1.
RX PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA Urlaub H., Meister G.;
RT "Proteomic and functional analysis of Argonaute-containing mRNA-protein
RT complexes in human cells.";
RL EMBO Rep. 8:1052-1060(2007).
RN [29]
RP FUNCTION, AND INTERACTION WITH DHX9.
RX PubMed=17531811; DOI=10.1016/j.molcel.2007.04.016;
RA Robb G.B., Rana T.M.;
RT "RNA helicase A interacts with RISC in human cells and functions in RISC
RT loading.";
RL Mol. Cell 26:523-537(2007).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DICER1;
RP EIF6; MOV10; RPL7A AND TARBP2, AND ASSOCIATION WITH THE 60S RIBOSOME.
RX PubMed=17507929; DOI=10.1038/nature05841;
RA Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I.,
RA Liebhaber S.A., Pasquinelli A.E., Shiekhattar R.;
RT "MicroRNA silencing through RISC recruitment of eIF6.";
RL Nature 447:823-828(2007).
RN [31]
RP FUNCTION.
RX PubMed=18048652; DOI=10.1126/science.1149460;
RA Vasudevan S., Tong Y., Steitz J.A.;
RT "Switching from repression to activation: microRNAs can up-regulate
RT translation.";
RL Science 318:1931-1934(2007).
RN [32]
RP FUNCTION, AND MUTAGENESIS OF ASP-597.
RX PubMed=18771919; DOI=10.1016/j.cub.2008.07.072;
RA Wu L., Fan J., Belasco J.G.;
RT "Importance of translation and nonnucleolytic ago proteins for on-target
RT RNA interference.";
RL Curr. Biol. 18:1327-1332(2008).
RN [33]
RP FUNCTION, INTERACTION WITH DICER1; P4HA1; P4HB; TNRC6A AND TNRC6B,
RP SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-700, AND MUTAGENESIS OF PRO-700.
RX PubMed=18690212; DOI=10.1038/nature07186;
RA Qi H.H., Ongusaha P.P., Myllyharju J., Cheng D., Pakkanen O., Shi Y.,
RA Lee S.W., Peng J., Shi Y.;
RT "Prolyl 4-hydroxylation regulates Argonaute 2 stability.";
RL Nature 455:421-424(2008).
RN [34]
RP FUNCTION, AND INTERACTION WITH DICER1 AND TARBP2.
RX PubMed=18178619; DOI=10.1073/pnas.0710869105;
RA MacRae I.J., Ma E., Zhou M., Robinson C.V., Doudna J.A.;
RT "In vitro reconstitution of the human RISC-loading complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:512-517(2008).
RN [35]
RP FUNCTION, INTERACTION WITH IMP8, AND SUBCELLULAR LOCATION.
RX PubMed=19167051; DOI=10.1016/j.cell.2008.12.023;
RA Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P.,
RA Kremmer E., Benes V., Urlaub H., Meister G.;
RT "Importin 8 is a gene silencing factor that targets argonaute proteins to
RT distinct mRNAs.";
RL Cell 136:496-507(2009).
RN [36]
RP INTERACTION WITH RBM4.
RX PubMed=19801630; DOI=10.1074/jbc.m109.032946;
RA Lin J.C., Tarn W.Y.;
RT "RNA-binding motif protein 4 translocates to cytoplasmic granules and
RT suppresses translation via argonaute2 during muscle cell differentiation.";
RL J. Biol. Chem. 284:34658-34665(2009).
RN [37]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA Longmore G.D., Bushell M., Sharp T.V.;
RT "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-
RT mediated gene silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [39]
RP INTERACTION WITH TNRC6C, AND MUTAGENESIS OF PHE-470 AND PHE-505.
RX PubMed=21981923; DOI=10.1016/j.molcel.2011.09.007;
RA Braun J.E., Huntzinger E., Fauser M., Izaurralde E.;
RT "GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA
RT targets.";
RL Mol. Cell 44:120-133(2011).
RN [40]
RP INTERACTION WITH MOV10.
RX PubMed=22791714; DOI=10.1074/jbc.m112.354001;
RA Liu C., Zhang X., Huang F., Yang B., Li J., Liu B., Luo H., Zhang P.,
RA Zhang H.;
RT "APOBEC3G inhibits microRNA-mediated repression of translation by
RT interfering with the interaction between Argonaute-2 and MOV10.";
RL J. Biol. Chem. 287:29373-29383(2012).
RN [41]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH APOBEC3A; APOBEC3C; APOBEC3F;
RP APOBEC3G AND APOBEC3H.
RX PubMed=22915799; DOI=10.1128/jvi.00595-12;
RA Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT "HIV-1 replication and APOBEC3 antiviral activity are not regulated by P
RT bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [42]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-673; PHE-676 AND
RP HIS-807.
RX PubMed=23746446; DOI=10.1016/j.celrep.2013.05.033;
RA Faehnle C.R., Elkayam E., Haase A.D., Hannon G.J., Joshua-Tor L.;
RT "The making of a slicer: activation of human Argonaute-1.";
RL Cell Rep. 3:1901-1909(2013).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387 AND SER-828, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [44]
RP PHOSPHORYLATION AT SER-387, AND SUBCELLULAR LOCATION.
RX PubMed=23603119; DOI=10.1016/j.molcel.2013.03.015;
RA Horman S.R., Janas M.M., Litterst C., Wang B., MacRae I.J., Sever M.J.,
RA Morrissey D.V., Graves P., Luo B., Umesalma S., Qi H.H., Miraglia L.J.,
RA Novina C.D., Orth A.P.;
RT "Akt-mediated phosphorylation of argonaute 2 downregulates cleavage and
RT upregulates translational repression of MicroRNA targets.";
RL Mol. Cell 50:356-367(2013).
RN [45]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TRIM71.
RX PubMed=23125361; DOI=10.1093/nar/gks1032;
RA Loedige I., Gaidatzis D., Sack R., Meister G., Filipowicz W.;
RT "The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA
RT function.";
RL Nucleic Acids Res. 41:518-532(2013).
RN [46]
RP INTERACTION WITH MOV10.
RX PubMed=24726324; DOI=10.1016/j.molcel.2014.03.017;
RA Gregersen L.H., Schueler M., Munschauer M., Mastrobuoni G., Chen W.,
RA Kempa S., Dieterich C., Landthaler M.;
RT "MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target
RT degradation by translocation along 3' UTRs.";
RL Mol. Cell 54:573-585(2014).
RN [47]
RP INTERACTION WITH CLNK.
RX PubMed=26009488; DOI=10.1016/j.bbrc.2015.05.046;
RA Xu M., Cai C., Sun X., Chen W., Li Q., Zhou H.;
RT "Clnk plays a role in TNF-alpha-induced cell death in murine fibrosarcoma
RT cell line L929.";
RL Biochem. Biophys. Res. Commun. 463:275-279(2015).
RN [48]
RP INTERACTION WITH RC3H1.
RX PubMed=25697406; DOI=10.1038/ncomms7253;
RA Srivastava M., Duan G., Kershaw N.J., Athanasopoulos V., Yeo J.H., Ose T.,
RA Hu D., Brown S.H., Jergic S., Patel H.R., Pratama A., Richards S.,
RA Verma A., Jones E.Y., Heissmeyer V., Preiss T., Dixon N.E., Chong M.M.,
RA Babon J.J., Vinuesa C.G.;
RT "Roquin binds microRNA-146a and Argonaute2 to regulate microRNA
RT homeostasis.";
RL Nat. Commun. 6:6253-6253(2015).
RN [49]
RP PHOSPHORYLATION AT SER-824; SER-828; SER-831 AND SER-834.
RX PubMed=28114302; DOI=10.1038/nature21025;
RA Golden R.J., Chen B., Li T., Braun J., Manjunath H., Chen X., Wu J.,
RA Schmid V., Chang T.C., Kopp F., Ramirez-Martinez A., Tagliabracci V.S.,
RA Chen Z.J., Xie Y., Mendell J.T.;
RT "An Argonaute phosphorylation cycle promotes microRNA-mediated silencing.";
RL Nature 542:197-202(2017).
RN [50]
RP INTERACTION WITH SND1.
RX PubMed=28546213; DOI=10.1126/science.aai9372;
RA Elbarbary R.A., Miyoshi K., Myers J.R., Du P., Ashton J.M., Tian B.,
RA Maquat L.E.;
RT "Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes
RT G1/S phase transition.";
RL Science 356:859-862(2017).
RN [51]
RP INTERACTION WITH GARRE1.
RX PubMed=29395067; DOI=10.1016/j.molcel.2017.12.020;
RA Youn J.Y., Dunham W.H., Hong S.J., Knight J.D.R., Bashkurov M., Chen G.I.,
RA Bagci H., Rathod B., MacLeod G., Eng S.W.M., Angers S., Morris Q.,
RA Fabian M., Cote J.F., Gingras A.C.;
RT "High-Density Proximity Mapping Reveals the Subcellular Organization of
RT mRNA-Associated Granules and Bodies.";
RL Mol. Cell 69:517.e11-532.e11(2018).
RN [52]
RP UBIQUITINATION.
RX PubMed=33184234; DOI=10.1126/science.abc9546;
RA Han J., LaVigne C.A., Jones B.T., Zhang H., Gillett F., Mendell J.T.;
RT "A ubiquitin ligase mediates target-directed microRNA decay independently
RT of tailing and trimming.";
RL Science 0:0-0(2020).
RN [53]
RP UBIQUITINATION.
RX PubMed=33184237; DOI=10.1126/science.abc9359;
RA Shi C.Y., Kingston E.R., Kleaveland B., Lin D.H., Stubna M.W., Bartel D.P.;
RT "The ZSWIM8 ubiquitin ligase mediates target-directed microRNA
RT degradation.";
RL Science 0:0-0(2020).
RN [54]
RP INVOLVEMENT IN LESKRES, VARIANTS LESKRES CYS-201; VAL-201; GLN-203;
RP MET-357; THR-364; PRO-367; SER-573; ARG-733; TYR-751 AND ARG-760,
RP CHARACTERIZATION OF VARIANTS LESKRES PRO-192; CYS-201; VAL-201; GLN-203;
RP MET-357; THR-364; PRO-367; SER-573; ARG-733; TYR-751 AND ARG-760,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-387, AND INTERACTION WITH
RP DICER1.
RX PubMed=33199684; DOI=10.1038/s41467-020-19572-5;
RA Lessel D., Zeitler D.M., Reijnders M.R.F., Kazantsev A., Hassani Nia F.,
RA Bartholomaeus A., Martens V., Bruckmann A., Graus V., McConkie-Rosell A.,
RA McDonald M., Lozic B., Tan E.S., Gerkes E., Johannsen J., Denecke J.,
RA Telegrafi A., Zonneveld-Huijssoon E., Lemmink H.H., Cham B.W.M.,
RA Kovacevic T., Ramsdell L., Foss K., Le Duc D., Mitter D., Syrbe S.,
RA Merkenschlager A., Sinnema M., Panis B., Lazier J., Osmond M., Hartley T.,
RA Mortreux J., Busa T., Missirian C., Prasun P., Luettgen S., Mannucci I.,
RA Lessel I., Schob C., Kindler S., Pappas J., Rabin R., Willemsen M.,
RA Gardeitchik T., Loehner K., Rump P., Dias K.R., Evans C.A., Andrews P.I.,
RA Roscioli T., Brunner H.G., Chijiwa C., Lewis M.E.S., Jamra R.A.,
RA Dyment D.A., Boycott K.M., Stegmann A.P.A., Kubisch C., Tan E.C.,
RA Mirzaa G.M., McWalter K., Kleefstra T., Pfundt R., Ignatova Z., Meister G.,
RA Kreienkamp H.J.;
RT "Germline AGO2 mutations impair RNA interference and human neurological
RT development.";
RL Nat. Commun. 11:5797-5797(2020).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 439-575 IN COMPLEX WITH AMP; CMP;
RP GMP AND PHOSPHATE.
RX PubMed=20505670; DOI=10.1038/nature09039;
RA Frank F., Sonenberg N., Nagar B.;
RT "Structural basis for 5'-nucleotide base-specific recognition of guide RNA
RT by human AGO2.";
RL Nature 465:818-822(2010).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 439-575 IN COMPLEX WITH 7-MGTPG
RP AND ATP.
RX PubMed=21475248; DOI=10.1038/embor.2011.48;
RA Frank F., Fabian M.R., Stepinski J., Jemielity J., Darzynkiewicz E.,
RA Sonenberg N., Nagar B.;
RT "Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID
RT domain.";
RL EMBO Rep. 12:415-420(2011).
RN [57]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH MIRNA-20A, AND GUIDE
RP RNA-BINDING.
RX PubMed=22682761; DOI=10.1016/j.cell.2012.05.017;
RA Elkayam E., Kuhn C.D., Tocilj A., Haase A.D., Greene E.M., Hannon G.J.,
RA Joshua-Tor L.;
RT "The structure of human argonaute-2 in complex with miR-20a.";
RL Cell 150:100-110(2012).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH RNA AND
RP L-TRYPTOPHAN, AND GUIDE RNA-BINDING.
RX PubMed=22539551; DOI=10.1126/science.1221551;
RA Schirle N.T., MacRae I.J.;
RT "The crystal structure of human Argonaute2.";
RL Science 336:1037-1040(2012).
CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi) by the RNA-
CC induced silencing complex (RISC). The 'minimal RISC' appears to include
CC AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short
CC interfering RNA (siRNA). These guide RNAs direct RISC to complementary
CC mRNAs that are targets for RISC-mediated gene silencing. The precise
CC mechanism of gene silencing depends on the degree of complementarity
CC between the miRNA or siRNA and its target. Binding of RISC to a
CC perfectly complementary mRNA generally results in silencing due to
CC endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of
CC RISC to a partially complementary mRNA results in silencing through
CC inhibition of translation, and this is independent of endonuclease
CC activity. May inhibit translation initiation by binding to the 7-
CC methylguanosine cap, thereby preventing the recruitment of the
CC translation initiation factor eIF4-E. May also inhibit translation
CC initiation via interaction with EIF6, which itself binds to the 60S
CC ribosomal subunit and prevents its association with the 40S ribosomal
CC subunit. The inhibition of translational initiation leads to the
CC accumulation of the affected mRNA in cytoplasmic processing bodies (P-
CC bodies), where mRNA degradation may subsequently occur. In some cases
CC RISC-mediated translational repression is also observed for miRNAs that
CC perfectly match the 3' untranslated region (3'-UTR). Can also up-
CC regulate the translation of specific mRNAs under certain growth
CC conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-
CC alpha) mRNA and up-regulates translation under conditions of serum
CC starvation. Also required for transcriptional gene silencing (TGS), in
CC which short RNAs known as antigene RNAs or agRNAs direct the
CC transcriptional repression of complementary promoter regions.
CC {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031,
CC ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15260970,
CC ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15337849,
CC ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16081698,
CC ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387,
CC ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216,
CC ECO:0000269|PubMed:16756390, ECO:0000269|PubMed:16936728,
CC ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929,
CC ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:17531811,
CC ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18048652,
CC ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212,
CC ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:19167051,
CC ECO:0000269|PubMed:23746446}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=endonucleolytic cleavage to 5'-phosphomonoester.;
CC EC=3.1.26.n2; Evidence={ECO:0000255|HAMAP-Rule:MF_03031,
CC ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:23746446};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15284456};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15284456};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000269|PubMed:15284456}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 nM for a synthetic 21-nucleotide single-stranded RNA
CC {ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15800637};
CC -!- SUBUNIT: Interacts with DICER1 through its Piwi domain and with TARBP2
CC during assembly of the RNA-induced silencing complex
CC (RISC)(PubMed:14749716, PubMed:16271387, PubMed:16289642,
CC PubMed:16357216, PubMed:15973356, PubMed:17507929, PubMed:18690212,
CC PubMed:18178619, PubMed:33199684). Together, DICER1, AGO2 and TARBP2
CC constitute the trimeric RISC loading complex (RLC), or micro-RNA
CC (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and
CC TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature
CC miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA
CC constitutes the minimal RISC and may subsequently dissociate from
CC DICER1 and TARBP2. Note however that the term RISC has also been used
CC to describe the trimeric RLC/miRLC. The formation of RISC complexes
CC containing siRNAs rather than miRNAs appears to occur independently of
CC DICER1. Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6,
CC DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1,
CC ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A,
CC TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and
CC XRN1. Associates with polysomes and messenger ribonucleoproteins
CC (mNRPs). Interacts with RBM4; the interaction is modulated under
CC stress-induced conditions, occurs under both cell proliferation and
CC differentiation conditions and in an RNA- and phosphorylation-
CC independent manner. Interacts with LIMD1, WTIP and AJUBA. Interacts
CC with TRIM71; the interaction increases in presence of RNA
CC (PubMed:23125361). Interacts with APOBEC3G in an RNA-dependent manner.
CC Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts
CC with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they
CC form a large RNA-induced silencing complex (RISC) (PubMed:17507929,
CC PubMed:24726324). Interacts with FMR1 (PubMed:14703574). Interacts with
CC ZFP36 (PubMed:15766526). Found in a complex, composed of AGO2, CHD7 and
CC FAM172A (By similarity). Interacts with RC3H1; the interaction is RNA
CC independent (PubMed:25697406). Interacts with SND1 (PubMed:14508492,
CC PubMed:28546213). Interacts with SYT11 (By similarity). Interacts with
CC CLNK (PubMed:26009488). Interacts with GARRE1 (PubMed:29395067).
CC {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031,
CC ECO:0000269|PubMed:14508492, ECO:0000269|PubMed:14703574,
CC ECO:0000269|PubMed:14749716, ECO:0000269|PubMed:15337849,
CC ECO:0000269|PubMed:15766526, ECO:0000269|PubMed:15973356,
CC ECO:0000269|PubMed:16081698, ECO:0000269|PubMed:16271387,
CC ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216,
CC ECO:0000269|PubMed:16699599, ECO:0000269|PubMed:16756390,
CC ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929,
CC ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:17932509,
CC ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212,
CC ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19801630,
CC ECO:0000269|PubMed:20505670, ECO:0000269|PubMed:20616046,
CC ECO:0000269|PubMed:21475248, ECO:0000269|PubMed:21981923,
CC ECO:0000269|PubMed:22539551, ECO:0000269|PubMed:22682761,
CC ECO:0000269|PubMed:22791714, ECO:0000269|PubMed:22915799,
CC ECO:0000269|PubMed:23125361, ECO:0000269|PubMed:24726324,
CC ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:26009488,
CC ECO:0000269|PubMed:28546213, ECO:0000269|PubMed:29395067}.
CC -!- INTERACTION:
CC Q9UKV8; Q9UL18: AGO1; NbExp=3; IntAct=EBI-528269, EBI-527363;
CC Q9UKV8; Q9UIV1: CNOT7; NbExp=2; IntAct=EBI-528269, EBI-2105113;
CC Q9UKV8; P26196: DDX6; NbExp=14; IntAct=EBI-528269, EBI-351257;
CC Q9UKV8; Q96C10: DHX58; NbExp=2; IntAct=EBI-528269, EBI-744193;
CC Q9UKV8; Q9UPY3: DICER1; NbExp=20; IntAct=EBI-528269, EBI-395506;
CC Q9UKV8; Q9UPY3-1: DICER1; NbExp=14; IntAct=EBI-528269, EBI-15569571;
CC Q9UKV8; G5E9A7: DMWD; NbExp=3; IntAct=EBI-528269, EBI-10976677;
CC Q9UKV8; P00533: EGFR; NbExp=11; IntAct=EBI-528269, EBI-297353;
CC Q9UKV8; Q13541: EIF4EBP1; NbExp=2; IntAct=EBI-528269, EBI-74090;
CC Q9UKV8; P22607: FGFR3; NbExp=3; IntAct=EBI-528269, EBI-348399;
CC Q9UKV8; Q02790: FKBP4; NbExp=2; IntAct=EBI-528269, EBI-1047444;
CC Q9UKV8; Q9BVP2: GNL3; NbExp=3; IntAct=EBI-528269, EBI-641642;
CC Q9UKV8; O15397: IPO8; NbExp=4; IntAct=EBI-528269, EBI-358808;
CC Q9UKV8; Q9UGP4: LIMD1; NbExp=11; IntAct=EBI-528269, EBI-2652871;
CC Q9UKV8; Q5S007: LRRK2; NbExp=3; IntAct=EBI-528269, EBI-5323863;
CC Q9UKV8; Q86UE4: MTDH; NbExp=3; IntAct=EBI-528269, EBI-1046588;
CC Q9UKV8; Q6IQ23: PLEKHA7; NbExp=7; IntAct=EBI-528269, EBI-2125301;
CC Q9UKV8; O75569: PRKRA; NbExp=5; IntAct=EBI-528269, EBI-713955;
CC Q9UKV8; P04156: PRNP; NbExp=4; IntAct=EBI-528269, EBI-977302;
CC Q9UKV8; Q15185: PTGES3; NbExp=3; IntAct=EBI-528269, EBI-1049387;
CC Q9UKV8; P63244: RACK1; NbExp=2; IntAct=EBI-528269, EBI-296739;
CC Q9UKV8; P06400: RB1; NbExp=3; IntAct=EBI-528269, EBI-491274;
CC Q9UKV8; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-528269, EBI-5235340;
CC Q9UKV8; Q15633: TARBP2; NbExp=12; IntAct=EBI-528269, EBI-978581;
CC Q9UKV8; Q9UHD2: TBK1; NbExp=2; IntAct=EBI-528269, EBI-356402;
CC Q9UKV8; A7MCY6: TBKBP1; NbExp=2; IntAct=EBI-528269, EBI-359969;
CC Q9UKV8; Q8NDV7: TNRC6A; NbExp=22; IntAct=EBI-528269, EBI-2269715;
CC Q9UKV8; Q9UPQ9: TNRC6B; NbExp=13; IntAct=EBI-528269, EBI-947158;
CC Q9UKV8; Q9UPQ9-2: TNRC6B; NbExp=4; IntAct=EBI-528269, EBI-6514011;
CC Q9UKV8; Q9HCJ0: TNRC6C; NbExp=4; IntAct=EBI-528269, EBI-6507625;
CC Q9UKV8; Q9HA38: ZMAT3; NbExp=5; IntAct=EBI-528269, EBI-2548480;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:23125361,
CC ECO:0000269|PubMed:23603119, ECO:0000269|PubMed:33199684}. Nucleus
CC {ECO:0000269|PubMed:23125361}. Note=Translational repression of mRNAs
CC results in their recruitment to P-bodies. Translocation to the nucleus
CC requires IMP8.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UKV8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKV8-2; Sequence=VSP_037001;
CC -!- DOMAIN: The Piwi domain may perform RNA cleavage by a mechanism similar
CC to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-
CC Glu (DDE) for metal ion coordination, this protein appears to utilize a
CC triad of Asp-Asp-His (DDH).
CC -!- PTM: Hydroxylated. 4-hydroxylation appears to enhance protein stability
CC but is not required for miRNA-binding or endonuclease activity.
CC {ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:18690212}.
CC -!- PTM: Ubiquitinated on surface-exposed lysines by a SCF-like E3
CC ubiquitin-protein ligase complex containing ZSWIM8 during target-
CC directed microRNA degradation (TDMD), a process that mediates
CC degradation of microRNAs (miRNAs) (PubMed:33184234, PubMed:33184237).
CC Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex
CC containing ZSWIM8 leads to its subsequent degradation, thereby exposing
CC miRNAs for degradation (PubMed:33184234, PubMed:33184237). ZSWIM8
CC recognizes and binds AGO2 when it is engaged with a TDMD target
CC (PubMed:33184237). {ECO:0000269|PubMed:33184234,
CC ECO:0000269|PubMed:33184237}.
CC -!- PTM: Phosphorylated. A phosphorylation cycle of C-terminal serine
CC cluster (Ser-824-Ser-834) regulates the release of target mRNAs.
CC Target-binding leads to phosphorylation of these residues by CSNK1A1,
CC which reduces the affinity of AGO2 for mRNA and enables target release.
CC The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues,
CC which primes AGO2 for binding a new target.
CC {ECO:0000269|PubMed:28114302}.
CC -!- PTM: Phosphorylation at Ser-387 by AKT3; leads to up-regulate
CC translational repression of microRNA target and down-regulate
CC endonucleolytic cleavage. {ECO:0000269|PubMed:23603119}.
CC -!- DISEASE: Lessel-Kreienkamp syndrome (LESKRES) [MIM:619149]: An
CC autosomal dominant disorder characterized by global developmental
CC delay, intellectual disability of variable degree, and speech and
CC language delay apparent from infancy or early childhood. Behavioral
CC disorders are observed in most patients. Additional variable features
CC include seizures, hypotonia, gait abnormalities, visual and cardiac
CC defects, and non-specific facial dysmorphism.
CC {ECO:0000269|PubMed:33199684}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH07633.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL76093.1; Type=Miscellaneous discrepancy; Note=cDNA contains a duplication of an internal sequence at the 5' end.; Evidence={ECO:0000305};
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DR EMBL; AC067931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107375; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007633; AAH07633.1; ALT_INIT; mRNA.
DR EMBL; BC018727; AAH18727.2; -; mRNA.
DR EMBL; BC125214; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY077717; AAL76093.1; ALT_SEQ; mRNA.
DR EMBL; BT007229; AAP35893.1; -; mRNA.
DR EMBL; AF121255; AAF13034.2; -; mRNA.
DR CCDS; CCDS55279.1; -. [Q9UKV8-2]
DR CCDS; CCDS6380.1; -. [Q9UKV8-1]
DR RefSeq; NP_001158095.1; NM_001164623.2. [Q9UKV8-2]
DR RefSeq; NP_036286.2; NM_012154.4. [Q9UKV8-1]
DR PDB; 3LUC; X-ray; 1.69 A; A/B/C=439-575.
DR PDB; 3LUD; X-ray; 2.10 A; A/B/C=439-575.
DR PDB; 3LUG; X-ray; 1.85 A; A/B/C=439-575.
DR PDB; 3LUH; X-ray; 2.00 A; A/B/C=439-575.
DR PDB; 3LUJ; X-ray; 1.80 A; A/B/C=439-575.
DR PDB; 3LUK; X-ray; 1.70 A; A/B/C=439-575.
DR PDB; 3QX8; X-ray; 2.30 A; A/B/C=439-575.
DR PDB; 3QX9; X-ray; 2.00 A; A/B/C=439-575.
DR PDB; 4F3T; X-ray; 2.25 A; A=1-859.
DR PDB; 4OLA; X-ray; 2.30 A; A=1-859.
DR PDB; 4OLB; X-ray; 2.90 A; A=1-859.
DR PDB; 4W5N; X-ray; 2.90 A; A=1-859.
DR PDB; 4W5O; X-ray; 1.80 A; A=1-859.
DR PDB; 4W5Q; X-ray; 3.10 A; A=1-859.
DR PDB; 4W5R; X-ray; 2.50 A; A=1-859.
DR PDB; 4W5T; X-ray; 2.50 A; A=1-859.
DR PDB; 4Z4C; X-ray; 2.30 A; A=1-859.
DR PDB; 4Z4D; X-ray; 1.60 A; A=1-859.
DR PDB; 4Z4E; X-ray; 1.80 A; A=1-859.
DR PDB; 4Z4F; X-ray; 2.80 A; A=1-859.
DR PDB; 4Z4G; X-ray; 2.70 A; A=1-859.
DR PDB; 4Z4H; X-ray; 2.50 A; A=1-859.
DR PDB; 4Z4I; X-ray; 2.80 A; A=1-859.
DR PDB; 5JS1; X-ray; 2.50 A; A=1-859.
DR PDB; 5JS2; X-ray; 2.95 A; A=1-859.
DR PDB; 5KI6; X-ray; 2.15 A; A=1-859.
DR PDB; 5T7B; X-ray; 2.53 A; A=1-859.
DR PDB; 5WEA; X-ray; 3.12 A; A=1-859.
DR PDB; 6CBD; X-ray; 2.20 A; A=1-859.
DR PDB; 6MDZ; X-ray; 3.40 A; A/B=1-859.
DR PDB; 6MFN; X-ray; 2.50 A; A=1-859.
DR PDB; 6MFR; X-ray; 3.60 A; A/B=1-859.
DR PDB; 6N4O; X-ray; 2.90 A; A=1-859.
DR PDB; 6NIT; X-ray; 3.80 A; A/B=1-859.
DR PDB; 6RA4; X-ray; 1.90 A; A/B=222-355.
DR PDB; 7C6B; X-ray; 1.70 A; A/B/C=440-578.
DR PDB; 7D7U; X-ray; 2.00 A; A/B/C=440-578.
DR PDB; 7KI3; X-ray; 3.00 A; A/D=1-859.
DR PDBsum; 3LUC; -.
DR PDBsum; 3LUD; -.
DR PDBsum; 3LUG; -.
DR PDBsum; 3LUH; -.
DR PDBsum; 3LUJ; -.
DR PDBsum; 3LUK; -.
DR PDBsum; 3QX8; -.
DR PDBsum; 3QX9; -.
DR PDBsum; 4F3T; -.
DR PDBsum; 4OLA; -.
DR PDBsum; 4OLB; -.
DR PDBsum; 4W5N; -.
DR PDBsum; 4W5O; -.
DR PDBsum; 4W5Q; -.
DR PDBsum; 4W5R; -.
DR PDBsum; 4W5T; -.
DR PDBsum; 4Z4C; -.
DR PDBsum; 4Z4D; -.
DR PDBsum; 4Z4E; -.
DR PDBsum; 4Z4F; -.
DR PDBsum; 4Z4G; -.
DR PDBsum; 4Z4H; -.
DR PDBsum; 4Z4I; -.
DR PDBsum; 5JS1; -.
DR PDBsum; 5JS2; -.
DR PDBsum; 5KI6; -.
DR PDBsum; 5T7B; -.
DR PDBsum; 5WEA; -.
DR PDBsum; 6CBD; -.
DR PDBsum; 6MDZ; -.
DR PDBsum; 6MFN; -.
DR PDBsum; 6MFR; -.
DR PDBsum; 6N4O; -.
DR PDBsum; 6NIT; -.
DR PDBsum; 6RA4; -.
DR PDBsum; 7C6B; -.
DR PDBsum; 7D7U; -.
DR PDBsum; 7KI3; -.
DR AlphaFoldDB; Q9UKV8; -.
DR SMR; Q9UKV8; -.
DR BioGRID; 118041; 399.
DR ComplexPortal; CPX-1072; RISC-loading complex, PRKRA variant.
DR ComplexPortal; CPX-134; RISC-loading complex, TARBP2 variant.
DR CORUM; Q9UKV8; -.
DR DIP; DIP-29194N; -.
DR IntAct; Q9UKV8; 218.
DR MINT; Q9UKV8; -.
DR STRING; 9606.ENSP00000220592; -.
DR BindingDB; Q9UKV8; -.
DR ChEMBL; CHEMBL4680043; -.
DR GlyGen; Q9UKV8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UKV8; -.
DR MetOSite; Q9UKV8; -.
DR PhosphoSitePlus; Q9UKV8; -.
DR SwissPalm; Q9UKV8; -.
DR BioMuta; AGO2; -.
DR DMDM; 229463006; -.
DR EPD; Q9UKV8; -.
DR jPOST; Q9UKV8; -.
DR MassIVE; Q9UKV8; -.
DR MaxQB; Q9UKV8; -.
DR PaxDb; Q9UKV8; -.
DR PeptideAtlas; Q9UKV8; -.
DR PRIDE; Q9UKV8; -.
DR ProteomicsDB; 84894; -. [Q9UKV8-1]
DR ProteomicsDB; 84895; -. [Q9UKV8-2]
DR Antibodypedia; 27626; 355 antibodies from 39 providers.
DR DNASU; 27161; -.
DR Ensembl; ENST00000220592.10; ENSP00000220592.5; ENSG00000123908.12. [Q9UKV8-1]
DR Ensembl; ENST00000519980.5; ENSP00000430176.1; ENSG00000123908.12. [Q9UKV8-2]
DR GeneID; 27161; -.
DR KEGG; hsa:27161; -.
DR MANE-Select; ENST00000220592.10; ENSP00000220592.5; NM_012154.5; NP_036286.2.
DR UCSC; uc003yvm.5; human. [Q9UKV8-1]
DR CTD; 27161; -.
DR DisGeNET; 27161; -.
DR GeneCards; AGO2; -.
DR HGNC; HGNC:3263; AGO2.
DR HPA; ENSG00000123908; Low tissue specificity.
DR MalaCards; AGO2; -.
DR MIM; 606229; gene.
DR MIM; 619149; phenotype.
DR neXtProt; NX_Q9UKV8; -.
DR OpenTargets; ENSG00000123908; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA27694; -.
DR VEuPathDB; HostDB:ENSG00000123908; -.
DR eggNOG; KOG1041; Eukaryota.
DR GeneTree; ENSGT00940000155239; -.
DR HOGENOM; CLU_004544_4_3_1; -.
DR InParanoid; Q9UKV8; -.
DR OMA; CFAQQQH; -.
DR OrthoDB; 159407at2759; -.
DR PhylomeDB; Q9UKV8; -.
DR TreeFam; TF101510; -.
DR PathwayCommons; Q9UKV8; -.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-426486; Small interfering RNA (siRNA) biogenesis.
DR Reactome; R-HSA-426496; Post-transcriptional silencing by small RNAs.
DR Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-HSA-8943723; Regulation of PTEN mRNA translation.
DR Reactome; R-HSA-8948700; Competing endogenous RNAs (ceRNAs) regulate PTEN translation.
DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR SignaLink; Q9UKV8; -.
DR SIGNOR; Q9UKV8; -.
DR BioGRID-ORCS; 27161; 45 hits in 1085 CRISPR screens.
DR ChiTaRS; AGO2; human.
DR EvolutionaryTrace; Q9UKV8; -.
DR GeneWiki; EIF2C2; -.
DR GenomeRNAi; 27161; -.
DR Pharos; Q9UKV8; Tbio.
DR PRO; PR:Q9UKV8; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9UKV8; protein.
DR Bgee; ENSG00000123908; Expressed in colonic epithelium and 196 other tissues.
DR ExpressionAtlas; Q9UKV8; baseline and differential.
DR Genevisible; Q9UKV8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0016442; C:RISC complex; IDA:UniProtKB.
DR GO; GO:0070578; C:RISC-loading complex; IDA:UniProtKB.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IMP:BHF-UCL.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:BHF-UCL.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:BHF-UCL.
DR GO; GO:0090624; F:endoribonuclease activity, cleaving miRNA-paired mRNA; IDA:BHF-UCL.
DR GO; GO:0070551; F:endoribonuclease activity, cleaving siRNA-paired mRNA; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035198; F:miRNA binding; IDA:BHF-UCL.
DR GO; GO:0098808; F:mRNA cap binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:BHF-UCL.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:BHF-UCL.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:BHF-UCL.
DR GO; GO:0035197; F:siRNA binding; IDA:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; NAS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0010586; P:miRNA metabolic process; IEA:Ensembl.
DR GO; GO:0035196; P:miRNA processing; IDA:BHF-UCL.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB.
DR GO; GO:0035279; P:miRNA-mediated gene silencing by mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0045947; P:negative regulation of translational initiation; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:1901165; P:positive regulation of trophoblast cell migration; IMP:BHF-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0035194; P:post-transcriptional gene silencing by RNA; TAS:Reactome.
DR GO; GO:0031054; P:pre-miRNA processing; IDA:UniProtKB.
DR GO; GO:0070922; P:RISC complex assembly; IDA:BHF-UCL.
DR GO; GO:0010501; P:RNA secondary structure unwinding; IDA:BHF-UCL.
DR GO; GO:0030422; P:siRNA processing; IDA:ComplexPortal.
DR GO; GO:0090625; P:siRNA-mediated gene silencing by mRNA destabilization; IDA:BHF-UCL.
DR GO; GO:0006412; P:translation; NAS:UniProtKB.
DR CDD; cd04657; Piwi_ago-like; 1.
DR DisProt; DP00736; -.
DR Gene3D; 3.30.420.10; -; 1.
DR HAMAP; MF_03031; AGO2; 1.
DR InterPro; IPR028602; AGO2.
DR InterPro; IPR014811; ArgoL1.
DR InterPro; IPR032472; ArgoL2.
DR InterPro; IPR032473; Argonaute_Mid_dom.
DR InterPro; IPR032474; Argonaute_N.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR036085; PAZ_dom_sf.
DR InterPro; IPR003165; Piwi.
DR InterPro; IPR045246; Piwi_ago-like.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF08699; ArgoL1; 1.
DR Pfam; PF16488; ArgoL2; 1.
DR Pfam; PF16487; ArgoMid; 1.
DR Pfam; PF16486; ArgoN; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 1.
DR SMART; SM01163; DUF1785; 1.
DR SMART; 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; Alternative splicing; Cytoplasm; Disease variant;
KW Endonuclease; Hydrolase; Hydroxylation; Intellectual disability; Magnesium;
KW Manganese; Metal-binding; Nitration; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Ribonucleoprotein; RNA-binding;
KW RNA-mediated gene silencing; Transcription; Transcription regulation;
KW Translation regulation; Ubl conjugation.
FT CHAIN 1..859
FT /note="Protein argonaute-2"
FT /id="PRO_0000194057"
FT DOMAIN 235..348
FT /note="PAZ"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT DOMAIN 517..818
FT /note="Piwi"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..316
FT /note="Interaction with guide RNA"
FT REGION 524..566
FT /note="Interaction with guide RNA"
FT REGION 587..590
FT /note="Interaction with GW182 family members"
FT /evidence="ECO:0000255"
FT REGION 650..660
FT /note="Interaction with GW182 family members"
FT /evidence="ECO:0000255"
FT REGION 709..710
FT /note="Interaction with guide RNA"
FT REGION 753..761
FT /note="Interaction with guide RNA"
FT REGION 790..812
FT /note="Interaction with guide RNA"
FT COMPBIAS 8..24
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 597
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT BINDING 669
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT BINDING 807
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT MOD_RES 2
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-
FT Rule:MF_03031"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23603119,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 700
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031,
FT ECO:0000269|PubMed:18690212"
FT MOD_RES 824
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28114302"
FT MOD_RES 828
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28114302,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28114302"
FT MOD_RES 834
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28114302"
FT VAR_SEQ 724..757
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037001"
FT VARIANT 192
FT /note="L -> P (in LESKRES; impairs shRNA-mediated
FT silencing. Does not affect targeting to P-bodies. Increases
FT binding to mRNA targets. Does not affect interaction with
FT DICER1. Decreased phosphorylation of the C-terminal serine
FT cluster. Does not affect phosphorylation of Ser-387)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085417"
FT VARIANT 201
FT /note="G -> C (in LESKRES; impairs shRNA-mediated
FT silencing. Does not affect targeting to P-bodies. Increases
FT binding to mRNA targets. Does not affect interaction with
FT DICER1. Decreased phosphorylation of the C-terminal serine
FT cluster. Does not affect phosphorylation of Ser-387)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085418"
FT VARIANT 201
FT /note="G -> V (in LESKRES)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085419"
FT VARIANT 203
FT /note="H -> Q (in LESKRES; impairs shRNA-mediated
FT silencing. Does not affect targeting to P-bodies. Increases
FT binding to mRNA targets. Does not affect interaction with
FT DICER1. Does not affect phosphorylation of the C-terminal
FT serine cluster. Does not affect phosphorylation of Ser-
FT 387)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085420"
FT VARIANT 357
FT /note="T -> M (in LESKRES)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085421"
FT VARIANT 364
FT /note="M -> T (in LESKRES; impairs shRNA-mediated
FT silencing. Does not affect targeting to P-bodies. Increases
FT binding to mRNA targets. Does not affect interaction with
FT DICER1. Decreased phosphorylation of the C-terminal serine
FT cluster. Does not affect phosphorylation of Ser-387)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085422"
FT VARIANT 367
FT /note="A -> P (in LESKRES; impairs shRNA-mediated
FT silencing. Decreased phosphorylation of the C-terminal
FT serine cluster. Increased binding to mRNA targets)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085423"
FT VARIANT 573
FT /note="G -> S (in LESKRES)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085424"
FT VARIANT 733
FT /note="G -> R (in LESKRES; complete loss of function.
FT Changes in the subcellular location pattern. Diffuse
FT location into the cytoplasm. Does not bind mRNA. Abolishes
FT interaction with DICER1. Abolishes phosphorylation of the
FT C-terminal serine cluster. Does not affect phosphorylation
FT of Ser-387)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085425"
FT VARIANT 751
FT /note="C -> Y (in LESKRES)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085426"
FT VARIANT 760
FT /note="S -> R (in LESKRES; impairs shRNA-mediated
FT silencing. Does not affect targeting to P-bodies. Increases
FT binding to mRNA targets. Does not affect interaction with
FT DICER1. Decreased phosphorylation of a C-terminal serine
FT cluster. Does not affect phosphorylation of Ser-387)"
FT /evidence="ECO:0000269|PubMed:33199684"
FT /id="VAR_085427"
FT MUTAGEN 140
FT /note="L->W: No effect."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 470
FT /note="F->V: No effect on miRNA-binding or target mRNA
FT cleavage. Abrogates binding to the 7-methylguanosine cap of
FT mRNA and prevents inhibition of translation. Abolishes
FT interaction with TNRC6C; when associated with V-505."
FT /evidence="ECO:0000269|PubMed:17524464,
FT ECO:0000269|PubMed:21981923"
FT MUTAGEN 470
FT /note="F->W: No effect on binding to the 7-methylguanosine
FT cap of mRNA or inhibition of translation."
FT /evidence="ECO:0000269|PubMed:17524464,
FT ECO:0000269|PubMed:21981923"
FT MUTAGEN 505
FT /note="F->V: No effect on miRNA-binding or target mRNA
FT cleavage. Abrogates binding to the 7-methylguanosine cap of
FT mRNA and prevents inhibition of translation and abolishes
FT interaction with TNRC6C; when associated with V-470."
FT /evidence="ECO:0000269|PubMed:17524464,
FT ECO:0000269|PubMed:21981923"
FT MUTAGEN 505
FT /note="F->W: No effect on binding to the 7-methylguanosine
FT cap of mRNA or inhibition of translation."
FT /evidence="ECO:0000269|PubMed:17524464,
FT ECO:0000269|PubMed:21981923"
FT MUTAGEN 533
FT /note="K->A: Impairs RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800629"
FT MUTAGEN 545
FT /note="Q->A: Impairs RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800629"
FT MUTAGEN 570
FT /note="K->A: Impairs RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800629"
FT MUTAGEN 597
FT /note="D->A: Abrogates RNA cleavage but does not affect
FT binding to siRNA or translational repression."
FT /evidence="ECO:0000269|PubMed:15284456,
FT ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:18771919"
FT MUTAGEN 633
FT /note="Q->A: No effect."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 633
FT /note="Q->R: Abrogates RNA cleavage. Binds siRNA."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 634
FT /note="H->P,A: Abrogates RNA cleavage. Binds siRNA."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 669
FT /note="D->A: Abrogates RNA cleavage but does not affect
FT binding to siRNA."
FT /evidence="ECO:0000269|PubMed:15284456,
FT ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16357216"
FT MUTAGEN 673
FT /note="E->A: Impairs RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800637,
FT ECO:0000269|PubMed:23746446"
FT MUTAGEN 673
FT /note="E->G: No effect on RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800637,
FT ECO:0000269|PubMed:23746446"
FT MUTAGEN 676
FT /note="F->A,I,M,R,Y: Impairs RNA cleavage."
FT /evidence="ECO:0000269|PubMed:23746446"
FT MUTAGEN 676
FT /note="F->V: Abrogates RNA cleavage."
FT /evidence="ECO:0000269|PubMed:23746446"
FT MUTAGEN 682
FT /note="H->Y: No effect."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 683
FT /note="E->G: No effect on RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800637"
FT MUTAGEN 700
FT /note="P->A: Reduced protein stability."
FT /evidence="ECO:0000269|PubMed:18690212"
FT MUTAGEN 704
FT /note="F->Y: No effect."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 744
FT /note="T->Y: No effect."
FT /evidence="ECO:0000269|PubMed:15284456"
FT MUTAGEN 807
FT /note="H->A,R: Abrogates RNA cleavage."
FT /evidence="ECO:0000269|PubMed:15800637,
FT ECO:0000269|PubMed:23746446"
FT CONFLICT 564
FT /note="C -> W (in Ref. 5; AAF13034)"
FT /evidence="ECO:0000305"
FT CONFLICT 589
FT /note="Q -> E (in Ref. 5; AAF13034)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="S -> R (in Ref. 5; AAF13034)"
FT /evidence="ECO:0000305"
FT CONFLICT 637
FT /note="E -> K (in Ref. 3; AAL76093)"
FT /evidence="ECO:0000305"
FT STRAND 35..48
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 53..63
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 68..81
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 82..86
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 107..110
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:4W5N"
FT STRAND 128..139
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 140..147
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 170..173
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:7KI3"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 196..207
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 210..225
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 230..238
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:7KI3"
FT STRAND 278..288
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:6RA4"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:4F3T"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:6RA4"
FT HELIX 308..316
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:6RA4"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:6RA4"
FT STRAND 348..351
FT /evidence="ECO:0007829|PDB:4OLB"
FT HELIX 358..368
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 372..386
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 392..396
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 406..412
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 422..425
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 464..480
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 490..494
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 498..500
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 501..511
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 517..522
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 528..537
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 538..540
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 544..548
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 550..553
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 557..570
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 585..588
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 591..599
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 603..605
FT /evidence="ECO:0007829|PDB:5KI6"
FT STRAND 610..617
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 619..622
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 625..633
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 642..657
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 662..669
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 676..694
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 701..709
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 710..712
FT /evidence="ECO:0007829|PDB:4W5Q"
FT STRAND 715..719
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 720..722
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 725..728
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 734..736
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 738..741
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 743..745
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 747..751
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 757..759
FT /evidence="ECO:0007829|PDB:6CBD"
FT STRAND 763..770
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 776..786
FT /evidence="ECO:0007829|PDB:4Z4D"
FT STRAND 793..795
FT /evidence="ECO:0007829|PDB:5KI6"
FT HELIX 801..816
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 817..820
FT /evidence="ECO:0007829|PDB:4Z4D"
FT HELIX 837..846
FT /evidence="ECO:0007829|PDB:4Z4D"
FT TURN 850..854
FT /evidence="ECO:0007829|PDB:4Z4D"
SQ SEQUENCE 859 AA; 97208 MW; 5C8552C43FC81345 CRC64;
MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP KIDIYHYELD
IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL YTAMPLPIGR DKVELEVTLP
GEGKDRIFKV SIKWVSCVSL QALHDALSGR LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS
FFTASEGCSN PLGGGREVWF GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF
KSIEEQQKPL TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES
GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ
TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM VKDEMTDVTG RVLQPPSILY
GGRNKAIATP VQGVWDMRNK QFHTGIEIKV WAIACFAPQR QCTEVHLKSF TEQLRKISRD
AGMPIQGQPC FCKYAQGADS VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL
GMATQCVQMK NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH
PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL IQFYKSTRFK
PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP GITFIVVQKR HHTRLFCTDK
NERVGKSGNI PAGTTVDTKI THPTEFDFYL CSHAGIQGTS RPSHYHVLWD DNRFSSDELQ
ILTYQLCHTY VRCTRSVSIP APAYYAHLVA FRARYHLVDK EHDSAEGSHT SGQSNGRDHQ
ALAKAVQVHQ DTLRTMYFA
