ID AGO2_MOUSE Reviewed; 860 AA. AC Q8CJG0; A1A563; Q4VAB3; Q571J6; DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 28-JUN-2023, entry version 170. DE RecName: Full=Protein argonaute-2 {ECO:0000255|HAMAP-Rule:MF_03031}; DE Short=Argonaute2 {ECO:0000255|HAMAP-Rule:MF_03031}; DE Short=mAgo2; 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=Piwi/argonaute family protein meIF2C2; DE AltName: Full=Protein slicer {ECO:0000255|HAMAP-Rule:MF_03031}; GN Name=Ago2; Synonyms=Eif2c2, Kiaa4215; 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]. RX PubMed=12526743; DOI=10.1016/s0960-9822(02)01394-5; RA Doi N., Zenno S., Ueda R., Ohki-Hamazaki H., Ui-Tei K., Saigo K.; RT "Short-interfering-RNA-mediated gene silencing in mammalian cells requires RT Dicer and eIF2C translation initiation factors."; RL Curr. Biol. 13:41-46(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=B5/EGFP; TISSUE=Trophoblast stem cell; 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 [LARGE SCALE MRNA] OF 158-860. RC TISSUE=Embryonic tail; RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., RA Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by RT screening of terminal sequences of cDNA clones randomly sampled from size- RT fractionated libraries."; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. 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 [5] RP INTERACTION WITH DICER1 AND TARBP2. 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 [6] RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16800626; DOI=10.1021/bi060474w; RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G., RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C., RA Bigelow D.J.; RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative RT disease."; RL Biochemistry 45:8009-8022(2006). RN [7] RP FUNCTION. RX PubMed=17626790; DOI=10.1101/gad.1565607; RA O'Carroll D., Mecklenbrauker I., Das P.P., Santana A., Koenig U., RA Enright A.J., Miska E.A., Tarakhovsky A.; RT "A Slicer-independent role for Argonaute 2 in hematopoiesis and the RT microRNA pathway."; RL Genes Dev. 21:1999-2004(2007). RN [8] RP FUNCTION. RX PubMed=19174539; DOI=10.1101/gad.1749809; RA Su H., Trombly M.I., Chen J., Wang X.; RT "Essential and overlapping functions for mammalian Argonautes in microRNA RT silencing."; RL Genes Dev. 23:304-317(2009). RN [9] RP INTERACTION WITH TRIM71. RX PubMed=19898466; DOI=10.1038/ncb1987; RA Rybak A., Fuchs H., Hadian K., Smirnova L., Wulczyn E.A., Michel G., RA Nitsch R., Krappmann D., Wulczyn F.G.; RT "The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin RT ligase for the miRNA pathway protein Ago2."; RL Nat. Cell Biol. 11:1411-1420(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC and Spleen; 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 [11] RP INTERACTION WITH TRIM71. RX PubMed=22508726; DOI=10.1101/gad.187641.112; RA Chen J., Lai F., Niswander L.; RT "The ubiquitin ligase mLin41 temporally promotes neural progenitor cell RT maintenance through FGF signaling."; RL Genes Dev. 26:803-815(2012). RN [12] RP INTERACTION WITH TRIM71. RX PubMed=22735451; DOI=10.1038/ncomms1909; RA Chang H.M., Martinez N.J., Thornton J.E., Hagan J.P., Nguyen K.D., RA Gregory R.I.; RT "Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote RT embryonic stem cell proliferation."; RL Nat. Commun. 3:923-923(2012). RN [13] RP INTERACTION WITH SND1 AND SYT11. RX PubMed=24882364; DOI=10.1016/j.febslet.2014.05.031; RA Milochau A., Lagree V., Benassy M.N., Chaignepain S., Papin J., RA Garcia-Arcos I., Lajoix A., Monterrat C., Coudert L., Schmitter J.M., RA Ochoa B., Lang J.; RT "Synaptotagmin 11 interacts with components of the RNA-induced silencing RT complex RISC in clonal pancreatic beta-cells."; RL FEBS Lett. 588:2217-2222(2014). RN [14] 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 [15] 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 [16] RP INTERACTION WITH FAM172A, AND IDENTIFICATION IN A COMPLEX WITH FAM172A; RP AGO2 AND CHD7. RX PubMed=29311329; DOI=10.1073/pnas.1715378115; RA Belanger C., Berube-Simard F.A., Leduc E., Bernas G., Campeau P.M., RA Lalani S.R., Martin D.M., Bielas S., Moccia A., Srivastava A., RA Silversides D.W., Pilon N.; RT "Dysregulation of cotranscriptional alternative splicing underlies CHARGE RT syndrome."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E620-E629(2018). 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. Regulates CC lymphoid and erythroid development and function, and this is CC independent of endonuclease activity. {ECO:0000255|HAMAP-Rule:MF_03031, CC ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:17626790, CC ECO:0000269|PubMed:19174539}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; CC EC=3.1.26.n2; Evidence={ECO:0000255|HAMAP-Rule:MF_03031}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- SUBUNIT: Interacts with DICER1 through its Piwi domain and with TARBP2 CC during assembly of the RNA-induced silencing complex (RISC). Together, CC DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex CC (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the CC RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs CC (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound CC to the mature miRNA constitutes the minimal RISC and may subsequently CC dissociate from DICER1 and TARBP2. Note however that the term RISC has CC also been used to describe the trimeric RLC/miRLC. The formation of CC RISC complexes containing siRNAs rather than miRNAs appears to occur CC independently of DICER1 (PubMed:16357216). Interacts with AGO1. Also CC interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, CC ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, CC P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with CC the P-body components DCP1A and XRN1. Associates with polysomes and CC messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the CC interaction is modulated under stress-induced conditions, occurs under CC both cell proliferation and differentiation conditions and in an CC RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP CC and AJUBA (By similarity). Interacts with TRIM71 (PubMed:19898466, CC PubMed:22508726, PubMed:22735451). Interacts with APOBEC3G in an RNA- CC dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and CC APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S CC ribosome subunit); they form a large RNA-induced silencing complex CC (RISC). Interacts with FMR1. Interacts with ZFP36 (By similarity). CC Interacts with RC3H1; the interaction is RNA independent CC (PubMed:25697406). Interacts with FAM172A (PubMed:29311329). Found in a CC complex composed of AGO2, CHD7 and FAM172A (PubMed:29311329). Interacts CC with SND1 and SYT11 (PubMed:24882364). Interacts with CLNK CC (PubMed:26009488). Interacts with GARRE1 (By similarity). CC {ECO:0000250|UniProtKB:Q9UKV8, ECO:0000255|HAMAP-Rule:MF_03031, CC ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:19898466, CC ECO:0000269|PubMed:22508726, ECO:0000269|PubMed:22735451, CC ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:26009488, CC ECO:0000269|PubMed:29311329}. CC -!- INTERACTION: CC Q8CJG0; Q4VGL6: Rc3h1; NbExp=2; IntAct=EBI-528299, EBI-2366263; CC Q8CJG0; Q9UPY3: DICER1; Xeno; NbExp=2; IntAct=EBI-528299, EBI-395506; CC Q8CJG0; P04156: PRNP; Xeno; NbExp=2; IntAct=EBI-528299, EBI-977302; CC Q8CJG0; P04273: PRNP; Xeno; NbExp=2; IntAct=EBI-528299, EBI-986426; CC Q8CJG0; Q9HCJ0: TNRC6C; Xeno; NbExp=3; IntAct=EBI-528299, EBI-6507625; CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP- CC Rule:MF_03031}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03031}. CC Note=Translational repression of mRNAs results in their recruitment to CC P-bodies. Translocation to the nucleus requires IMP8. CC {ECO:0000255|HAMAP-Rule:MF_03031}. CC -!- TISSUE SPECIFICITY: Ubiquitous expression in 9.5 day embryos with CC highest levels in forebrain, heart, limb buds, and branchial arches. CC {ECO:0000269|PubMed:15284456}. 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). {ECO:0000255|HAMAP-Rule:MF_03031}. 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}. 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). Ubiquitination by the SCF-like E3 CC ubiquitin-protein ligase complex containing ZSWIM8 leads to its CC subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 CC recognizes and binds AGO2 when it is engaged with a TDMD target. CC {ECO:0000250|UniProtKB:Q9UKV8}. CC -!- PTM: Phosphorylation at Ser-388 by AKT3; leads to up-regulate CC translational repression of microRNA target and down-regulate CC endonucleolytic cleavage. {ECO:0000250|UniProtKB:Q9UKV8}. CC -!- PTM: A phosphorylation cycle of C-terminal serine cluster (Ser-825-Ser- CC 835) regulates the release of target mRNAs. Target-binding leads to CC phosphorylation of these residues by CSNK1A1, which reduces the CC affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C CC phosphatase complex dephosphorylates the residues, which primes AGO2 CC for binding a new target. {ECO:0000250|UniProtKB:Q9UKV8}. CC -!- DISRUPTION PHENOTYPE: Embryonic death with a strong defect in neural CC tube closure and apparent cardiac failure. CC {ECO:0000269|PubMed:15284456}. CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily. CC {ECO:0000255|HAMAP-Rule:MF_03031}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH96465.1; 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; AB081472; BAC15767.1; -; mRNA. DR EMBL; BC096465; AAH96465.1; ALT_INIT; mRNA. DR EMBL; BC128379; AAI28380.1; -; mRNA. DR EMBL; BC129922; AAI29923.1; -; mRNA. DR EMBL; AK220193; BAD90378.1; -; mRNA. DR CCDS; CCDS37098.1; -. DR RefSeq; NP_694818.3; NM_153178.4. DR AlphaFoldDB; Q8CJG0; -. DR SMR; Q8CJG0; -. DR BioGRID; 232092; 59. DR ComplexPortal; CPX-1073; RISC-loading complex, PRKRA variant. DR ComplexPortal; CPX-135; RISC-loading complex, TARBP2 variant. DR DIP; DIP-35014N; -. DR IntAct; Q8CJG0; 57. DR MINT; Q8CJG0; -. DR STRING; 10090.ENSMUSP00000042207; -. DR GlyGen; Q8CJG0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8CJG0; -. DR PhosphoSitePlus; Q8CJG0; -. DR SwissPalm; Q8CJG0; -. DR EPD; Q8CJG0; -. DR jPOST; Q8CJG0; -. DR MaxQB; Q8CJG0; -. DR PaxDb; Q8CJG0; -. DR PeptideAtlas; Q8CJG0; -. DR ProteomicsDB; 285770; -. DR Antibodypedia; 27626; 394 antibodies from 39 providers. DR DNASU; 239528; -. DR Ensembl; ENSMUST00000044113; ENSMUSP00000042207; ENSMUSG00000036698. DR GeneID; 239528; -. DR KEGG; mmu:239528; -. DR UCSC; uc007wbu.2; mouse. DR AGR; MGI:2446632; -. DR CTD; 27161; -. DR MGI; MGI:2446632; Ago2. DR VEuPathDB; HostDB:ENSMUSG00000036698; -. DR eggNOG; KOG1041; Eukaryota. DR GeneTree; ENSGT00940000155239; -. DR HOGENOM; CLU_004544_4_3_1; -. DR InParanoid; Q8CJG0; -. DR OMA; CFAQQQH; -. DR OrthoDB; 3060088at2759; -. DR PhylomeDB; Q8CJG0; -. DR TreeFam; TF101510; -. DR Reactome; R-MMU-203927; MicroRNA (miRNA) biogenesis. DR Reactome; R-MMU-426486; Small interfering RNA (siRNA) biogenesis. DR Reactome; R-MMU-426496; Post-transcriptional silencing by small RNAs. DR Reactome; R-MMU-5578749; Transcriptional regulation by small RNAs. DR BioGRID-ORCS; 239528; 18 hits in 78 CRISPR screens. DR ChiTaRS; Ago2; mouse. DR PRO; PR:Q8CJG0; -. DR Proteomes; UP000000589; Chromosome 15. DR RNAct; Q8CJG0; protein. DR Bgee; ENSMUSG00000036698; Expressed in ascending aorta and 219 other tissues. DR Genevisible; Q8CJG0; MM. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0030425; C:dendrite; IDA:MGI. DR GO; GO:0070062; C:extracellular exosome; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; ISO:MGI. DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0000932; C:P-body; IDA:MGI. DR GO; GO:0005844; C:polysome; ISS:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI. DR GO; GO:0016442; C:RISC complex; IDA:BHF-UCL. DR GO; GO:0070578; C:RISC-loading complex; IDA:BHF-UCL. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISO:MGI. DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI. DR GO; GO:0090624; F:endoribonuclease activity, cleaving miRNA-paired mRNA; ISO:MGI. DR GO; GO:0070551; F:endoribonuclease activity, cleaving siRNA-paired mRNA; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0035198; F:miRNA binding; IDA:MGI. DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; ISO:MGI. DR GO; GO:0003729; F:mRNA binding; IDA:MGI. DR GO; GO:0098808; F:mRNA cap binding; ISO:MGI. DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB. DR GO; GO:0003723; F:RNA binding; IDA:MGI. DR GO; GO:0004521; F:RNA endonuclease activity; IDA:MGI. DR GO; GO:0000993; F:RNA polymerase II complex binding; ISO:MGI. DR GO; GO:0003727; F:single-stranded RNA binding; ISO:MGI. DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0010586; P:miRNA metabolic process; IDA:MGI. DR GO; GO:0035196; P:miRNA processing; IMP:MGI. DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB. DR GO; GO:0035279; P:miRNA-mediated gene silencing by mRNA destabilization; IDA:BHF-UCL. DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; ISO:MGI. DR GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI. DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:UniProtKB. DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI. DR GO; GO:1901165; P:positive regulation of trophoblast cell migration; ISO:MGI. DR GO; GO:0009791; P:post-embryonic development; IMP:MGI. DR GO; GO:0031054; P:pre-miRNA processing; IDA:BHF-UCL. DR GO; GO:0070922; P:RISC complex assembly; ISO:MGI. DR GO; GO:0010501; P:RNA secondary structure unwinding; ISO:MGI. DR GO; GO:0031047; P:RNA-mediated gene silencing; IMP:UniProtKB. DR GO; GO:0030422; P:siRNA processing; ISO:MGI. DR GO; GO:0090625; P:siRNA-mediated gene silencing by mRNA destabilization; ISO:MGI. DR CDD; cd02846; PAZ_argonaute_like; 1. DR CDD; cd04657; Piwi_ago-like; 1. DR Gene3D; 3.40.50.2300; -; 1. DR Gene3D; 2.170.260.10; paz domain; 1. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1. DR 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 PANTHER; PTHR22891; EUKARYOTIC TRANSLATION INITIATION FACTOR 2C; 1. DR PANTHER; PTHR22891:SF59; PROTEIN ARGONAUTE-2; 1. DR Pfam; PF08699; ArgoL1; 1. DR Pfam; PF16488; ArgoL2; 1. DR Pfam; PF16487; ArgoMid; 1. DR Pfam; PF16486; ArgoN; 1. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF02171; Piwi; 1. DR SMART; SM01163; DUF1785; 1. DR SMART; SM00949; PAZ; 1. DR SMART; SM00950; Piwi; 1. DR SUPFAM; SSF101690; PAZ domain; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS50822; PIWI; 1. PE 1: Evidence at protein level; KW Cytoplasm; Developmental protein; Differentiation; Endonuclease; Hydrolase; KW Hydroxylation; Magnesium; Manganese; Metal-binding; Nitration; Nuclease; KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Ribonucleoprotein; KW RNA-binding; RNA-mediated gene silencing; Transcription; KW Transcription regulation; Translation regulation; Ubl conjugation. FT CHAIN 1..860 FT /note="Protein argonaute-2" FT /id="PRO_0000194058" FT DOMAIN 230..349 FT /note="PAZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142" FT DOMAIN 518..819 FT /note="Piwi" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031" FT REGION 312..317 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000250" FT REGION 525..567 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000250" FT REGION 588..591 FT /note="Interaction with GW182 family members" FT /evidence="ECO:0000255" FT REGION 651..661 FT /note="Interaction with GW182 family members" FT /evidence="ECO:0000255" FT REGION 710..711 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000250" FT REGION 754..762 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000250" FT REGION 791..813 FT /note="Interaction with guide RNA" FT /evidence="ECO:0000250" FT BINDING 598 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031" FT BINDING 670 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031" FT BINDING 808 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031" FT MOD_RES 2 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0007744|PubMed:16800626" FT MOD_RES 388 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UKV8" FT MOD_RES 701 FT /note="4-hydroxyproline" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031" FT MOD_RES 825 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UKV8" FT MOD_RES 829 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UKV8" FT MOD_RES 832 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UKV8" FT MOD_RES 835 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UKV8" FT CONFLICT 65 FT /note="E -> G (in Ref. 2; AAH96465)" FT /evidence="ECO:0000305" FT CONFLICT 67 FT /note="C -> R (in Ref. 1; BAC15767)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="F -> L (in Ref. 1; BAC15767)" FT /evidence="ECO:0000305" FT CONFLICT 360 FT /note="N -> D (in Ref. 1; BAC15767)" FT /evidence="ECO:0000305" FT CONFLICT 563 FT /note="N -> D (in Ref. 2; AAH96465)" FT /evidence="ECO:0000305" FT CONFLICT 711 FT /note="R -> P (in Ref. 2; AAH96465)" FT /evidence="ECO:0000305" FT CONFLICT 761 FT /note="S -> G (in Ref. 1; BAC15767)" FT /evidence="ECO:0000305" SQ SEQUENCE 860 AA; 97304 MW; A4E13C633846062C CRC64; MYSGAGPVLA SPAPTTSPIP GYAFKPPPRP DFGTTGRTIK LQANFFEMDI PKIDIYHYEL DIKPEKCPRR VNREIVEHMV QHFKTQIFGD RKPVFDGRKN LYTAMPLPIG RDKVELEVTL PGEGKDRIFK VSIKWVSCVS LQALHDALSG RLPSVPFETI QALDVVMRHL PSMRYTPVGR SFFTASEGCS NPLGGGREVW FGFHQSVRPS LWKMMLNIDV SATAFYKAQP VIEFVCEVLD FKSIEEQQKP LTDSQRVKFT KEIKGLKVEI THCGQMKRKY RVCNVTRRPA SHQTFPLQQE SGQTVECTVA QYFKDRHKLV LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN QTSTMIRATA RSAPDRQEEI SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL YGGRNKAIAT PVQGVWDMRN KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS FTEQLRKISR DAGMPIQGQP CFCKYAQGAD SVEPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV LGMATQCVQM KNVQRTTPQT LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT HPPAGDGKKP SIAAVVGSMD AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF KPTRIIFYRD GVSEGQFQQV LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD KNERVGKSGN IPAGTTVDTK ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL QILTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA //