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 14-DEC-2011, entry version 79. DE RecName: Full=Protein argonaute-2; DE Short=Argonaute2; DE Short=mAgo2; DE EC=3.1.26.n2; 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=Eif2c2; Synonyms=Ago2, 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). CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi) by the CC RNA-induced silencing complex (RISC). The 'minimal RISC' appears CC to include EIF2C2/AGO2 bound to a short guide RNA such as a CC microRNA (miRNA) or short interfering RNA (siRNA). These guide CC RNAs direct RISC to complementary mRNAs that are targets for RISC- CC mediated gene silencing. The precise mechanism of gene silencing CC depends on the degree of complementarity between the miRNA or CC siRNA and its target. Binding of RISC to a perfectly complementary CC mRNA generally results in silencing due to endonucleolytic CC cleavage of the mRNA specifically by EIF2C2/AGO2. Binding of RISC CC 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 CC 60S ribosomal subunit and prevents its association with the 40S CC ribosomal subunit. The inhibition of translational initiation CC leads to the accumulation of the affected mRNA in cytoplasmic CC processing bodies (P-bodies), where mRNA degradation may CC subsequently occur. In some cases RISC-mediated translational CC repression is also observed for miRNAs that perfectly match the 3' CC untranslated region (3'-UTR). May also upregulate the translation CC of specific mRNAs under certain growth conditions. Binds to the AU CC element of the 3'-UTR of the TNF (TNF-alpha) mRNA and upregulates CC translation under conditions of serum starvation. May also be CC required for transcriptional gene silencing (TGS), in which short CC RNAs known as antigene RNAs or agRNAs direct the transcriptional CC repression of complementary promoter regions. Regulates lymphoid CC and erythroid development and function, and this is independent of CC endonuclease activity. CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to 5'- CC phosphomonoester. CC -!- SUBUNIT: Interacts with EIF2C1/AGO1. Also interacts with DDB1, CC DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, EIF6, ELAVL, FXR1, CC GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, CC P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts CC with the P-body components DCP1A and XRN1. Associates with CC polysomes and messenger ribonucleoproteins (mNRPs). Interacts with CC RBM4; the interaction is modulated under stress-induced CC conditions, occurs under both cell proliferation and CC differentiation conditions and in a RNA- and phosphorylation- CC independent manner (By similarity). Interacts with DICER1 through CC its Piwi domain and with TARBP2 during assembly of the RNA-induced CC silencing complex (RISC). Together, DICER1, EIF2C2/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 CC mature miRNAs and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 CC bound to the mature miRNA constitutes the minimal RISC and may CC subsequently dissociate from DICER1 and TARBP2. Note however that CC the term RISC has also been used to describe the trimeric CC RLC/miRLC. The formation of RISC complexes containing siRNAs CC rather than miRNAs appears to occur independently of DICER1. 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 triad CC of Asp-Asp-Glu (DDE) for metal ion coordination, this protein CC appears to utilize a triad of Asp-Asp-His (DDH) (By 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.475937; -. DR ProteinModelPortal; Q8CJG0; -. DR SMR; Q8CJG0; 223-390, 441-575. DR DIP; DIP-35014N; -. DR IntAct; Q8CJG0; 1. DR STRING; Q8CJG0; -. DR PhosphoSite; Q8CJG0; -. DR PRIDE; Q8CJG0; -. DR Ensembl; ENSMUST00000044113; ENSMUSP00000042207; ENSMUSG00000036698. DR GeneID; 239528; -. DR KEGG; mmu:239528; -. DR CTD; 27161; -. DR MGI; MGI:2446632; Eif2c2. DR HOGENOM; HBG717005; -. DR InParanoid; Q8CJG0; -. 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; IEA:UniProtKB-SubCell. 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:0005515; F:protein binding; IPI:IntAct. 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:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. 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: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 InterPro; IPR014811; DUF1785. DR InterPro; IPR003100; PAZ. DR InterPro; IPR003165; Piwi. DR InterPro; IPR012337; RNaseH-like_dom. DR KO; K11593; -. 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 //