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 26-JUN-2013, entry version 93. DE RecName: Full=Protein argonaute-2; DE Short=Argonaute2; DE Short=mAgo2; DE EC=3.1.26.n2; DE AltName: Full=Argonaute RISC catalytic component 2; DE AltName: Full=Eukaryotic translation initiation factor 2C 2; DE Short=eIF-2C 2; DE Short=eIF2C 2; DE AltName: Full=Piwi/argonaute family protein meIF2C2; DE AltName: Full=Protein slicer; GN Name=Ago2; Synonyms=Eif2c2, Kiaa4215; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; 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 RT requires 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 RT project: 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. RT The complete nucleotide sequences of mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-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., RA Song J.-J., 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- RT miRNA."; RL Genes Dev. 19:2979-2990(2005). RN [6] RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-2, AND MASS SPECTROMETRY. 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., RA Lacan G., Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., RA Squier T.C., Bigelow D.J.; RT "Endogenously nitrated proteins in mouse brain: links to RT neurodegenerative 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 RT microRNA 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 RT ubiquitin ligase for the miRNA pathway protein Ago2."; RL Nat. Cell Biol. 11:1411-1420(2009). RN [10] 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 RT cell maintenance through FGF signaling."; RL Genes Dev. 26:803-815(2012). RN [11] 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 RT promote embryonic stem cell proliferation."; RL Nat. Commun. 3:923-923(2012). CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi) by the CC RNA-induced silencing complex (RISC). The 'minimal RISC' appears CC to include AGO2 bound to a short guide RNA such as a microRNA CC (miRNA) or short interfering RNA (siRNA). These guide RNAs direct CC RISC to complementary mRNAs that are targets for RISC-mediated CC gene silencing. The precise mechanism of gene silencing depends on CC the degree of complementarity between the miRNA or siRNA and its CC target. Binding of RISC to a perfectly complementary mRNA CC generally results in silencing due to endonucleolytic cleavage of CC the mRNA specifically by AGO2. Binding of RISC to a partially CC complementary mRNA results in silencing through inhibition of CC translation, and this is independent of endonuclease activity. May CC inhibit translation initiation by binding to the 7-methylguanosine CC cap, thereby preventing the recruitment of the translation CC initiation factor eIF4-E. May also inhibit translation initiation CC via interaction with EIF6, which itself binds to the 60S ribosomal CC 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 CC (P-bodies), where mRNA degradation may subsequently occur. In some CC cases RISC-mediated translational repression is also observed for CC miRNAs that perfectly match the 3' untranslated region (3'-UTR). CC Can also up-regulate the translation of specific mRNAs under CC certain growth conditions. Binds to the AU element of the 3'-UTR CC of the TNF (TNF-alpha) mRNA and up-regulates translation under CC conditions of serum starvation. Also required for transcriptional CC gene silencing (TGS), in which short RNAs known as antigene RNAs CC or agRNAs direct the transcriptional repression of complementary CC promoter regions. Regulates lymphoid and erythroid development and CC function, and this is independent of endonuclease activity. CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to 5'- CC phosphomonoester. CC -!- SUBUNIT: Interacts with AGO1. Also interacts with DDB1, DDX5, CC DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, EIF6, ELAVL, FXR1, GEMIN4, CC HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, P4HA1, CC P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with CC the P-body components DCP1A and XRN1. Associates with polysomes CC and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the CC interaction is modulated under stress-induced conditions, occurs CC under both cell proliferation and differentiation conditions and CC in a RNA- and phosphorylation-independent manner (By similarity). CC Interacts with DICER1 through its Piwi domain and with TARBP2 CC during assembly of the RNA-induced silencing complex (RISC). CC Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC CC loading complex (RLC), or micro-RNA (miRNA) loading complex CC (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to CC process precursor miRNAs (pre-miRNAs) to mature miRNAs and then CC load them onto AGO2. AGO2 bound to the mature miRNA constitutes CC the minimal RISC and may subsequently dissociate from DICER1 and CC TARBP2. Note however that the term RISC has also been used to CC describe the trimeric RLC/miRLC. The formation of RISC complexes CC containing siRNAs rather than miRNAs appears to occur CC independently of DICER1. Interacts with LIMD1, WTIP and AJUBA (By CC similarity). Interacts with TRIM71. Interacts with APOBEC3G in an CC RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F CC and APOBEC3H (By similarity). CC -!- INTERACTION: CC Q9UPY3:DICER1 (xeno); NbExp=2; IntAct=EBI-528299, EBI-395506; CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body (By similarity). Nucleus CC (By similarity). Note=Translational repression of mRNAs results in CC their recruitment to P-bodies. Translocation to the nucleus CC requires IMP8 (By similarity). CC -!- TISSUE SPECIFICITY: Ubiquitous expression in 9.5 day embryos with CC highest levels in forebrain, heart, limb buds, and branchial CC arches. CC -!- DOMAIN: The Piwi domain may perform RNA cleavage by a mechanism CC similar to that of RNase H. However, while RNase H utilizes a CC triad of Asp-Asp-Glu (DDE) for metal ion coordination, this CC protein appears to utilize a triad of Asp-Asp-His (DDH) (By CC similarity). CC -!- PTM: Hydroxylated. 4-hydroxylation appears to enhance protein CC stability but is not required for miRNA-binding or endonuclease CC activity (By similarity). CC -!- DISRUPTION PHENOTYPE: Embryonic death with a strong defect in CC neural tube closure and apparent cardiac failure. CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily. CC -!- SIMILARITY: Contains 1 PAZ domain. CC -!- SIMILARITY: Contains 1 Piwi domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAH96465.1; Type=Erroneous initiation; 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 IPI; IPI00229988; -. DR RefSeq; NP_694818.3; NM_153178.4. DR UniGene; Mm.23095; -. DR UniGene; Mm.391971; -. DR UniGene; Mm.440409; -. DR UniGene; Mm.476931; -. DR UniGene; Mm.486474; -. DR UniGene; Mm.490340; -. DR ProteinModelPortal; Q8CJG0; -. DR SMR; Q8CJG0; 24-860. DR DIP; DIP-35014N; -. DR IntAct; Q8CJG0; 4. DR PhosphoSite; Q8CJG0; -. DR PaxDb; Q8CJG0; -. DR PRIDE; Q8CJG0; -. DR Ensembl; ENSMUST00000044113; ENSMUSP00000042207; ENSMUSG00000036698. DR GeneID; 239528; -. DR KEGG; mmu:239528; -. DR UCSC; uc007wbu.2; mouse. DR CTD; 27161; -. DR MGI; MGI:2446632; Ago2. DR eggNOG; NOG279895; -. DR GeneTree; ENSGT00640000091310; -. DR HOGENOM; HOG000116043; -. DR HOVERGEN; HBG006101; -. DR InParanoid; A1A563; -. DR KO; K11593; -. DR OMA; AIKWMSC; -. DR OrthoDB; EOG4229J0; -. DR NextBio; 384151; -. DR ArrayExpress; Q8CJG0; -. DR Bgee; Q8CJG0; -. DR CleanEx; MM_EIF2C2; -. DR Genevestigator; Q8CJG0; -. DR GermOnline; ENSMUSG00000036698; Mus musculus. DR GO; GO:0000932; C:cytoplasmic mRNA processing body; IDA:MGI. DR GO; GO:0035068; C:micro-ribonucleoprotein complex; ISS:UniProtKB. DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005844; C:polysome; ISS:UniProtKB. DR GO; GO:0016442; C:RNA-induced silencing complex; ISS:UniProtKB. 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:0003729; F:mRNA binding; IDA:MGI. DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB. DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0035279; P:mRNA cleavage involved in gene silencing by miRNA; ISS:UniProtKB. DR GO; GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; ISS:UniProtKB. DR GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB. 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:0009791; P:post-embryonic development; IMP:MGI. DR GO; GO:0031054; P:pre-miRNA processing; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR HAMAP; MF_03031; AGO2; 1; -. DR InterPro; IPR014811; DUF1785. DR InterPro; IPR003100; PAZ. DR InterPro; IPR003165; Piwi. DR InterPro; IPR012337; RNaseH-like_dom. DR Pfam; PF08699; DUF1785; 1. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF02171; Piwi; 1. DR SMART; SM00949; PAZ; 1. DR SMART; SM00950; Piwi; 1. DR SUPFAM; SSF101690; PAZ; 1. DR SUPFAM; SSF53098; RNaseH_fold; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS50822; PIWI; 1. PE 1: Evidence at protein level; KW Complete proteome; Cytoplasm; Developmental protein; Differentiation; KW Endonuclease; Hydrolase; Hydroxylation; Metal-binding; Nitration; KW Nuclease; Nucleus; Reference proteome; Repressor; Ribonucleoprotein; KW RNA-binding; RNA-mediated gene silencing; Transcription; KW Transcription regulation; Translation regulation. FT CHAIN 1 860 Protein argonaute-2. FT /FTId=PRO_0000194058. FT DOMAIN 236 349 PAZ. FT DOMAIN 518 819 Piwi. FT METAL 598 598 Divalent metal cation (By similarity). FT METAL 670 670 Divalent metal cation (By similarity). FT METAL 808 808 Divalent metal cation (By similarity). FT MOD_RES 2 2 Nitrated tyrosine. FT MOD_RES 701 701 4-hydroxyproline (By similarity). FT CONFLICT 65 65 E -> G (in Ref. 2; AAH96465). FT CONFLICT 67 67 C -> R (in Ref. 1; BAC15767). FT CONFLICT 129 129 F -> L (in Ref. 1; BAC15767). FT CONFLICT 360 360 N -> D (in Ref. 1; BAC15767). FT CONFLICT 563 563 N -> D (in Ref. 2; AAH96465). FT CONFLICT 711 711 R -> P (in Ref. 2; AAH96465). FT CONFLICT 761 761 S -> G (in Ref. 1; BAC15767). 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 //