ID AGO2_RAT Reviewed; 860 AA. AC Q9QZ81; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 14-NOV-2003, sequence version 2. DT 13-OCT-2009, entry version 53. DE RecName: Full=Protein argonaute-2; DE EC=3.1.26.n1; DE AltName: Full=Argonaute2; DE AltName: Full=Protein slicer; DE AltName: Full=Eukaryotic translation initiation factor 2C 2; DE Short=eIF-2C 2; DE Short=eIF2C 2; DE AltName: Full=Golgi ER protein 95 kDa; DE Short=GERp95; GN Name=Eif2c2; Synonyms=Ago2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Hepatoma; RX MEDLINE=99443791; PubMed=10512872; RA Cikaluk D.E., Tahbaz N., Hendricks L.C., DiMattia G.E., Hansen D., RA Pilgrim D., Hobman T.C.; RT "GERp95, a membrane-associated protein that belongs to a family of RT proteins involved in stem cell differentiation."; RL Mol. Biol. Cell 10:3357-3372(1999). 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). Can 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. Also required CC for transcriptional gene silencing (TGS), in which short RNAs CC known as antigene RNAs or agRNAs direct the transcriptional CC repression of complementary promoter regions (By similarity). CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to 5'- CC phosphomonoester. CC -!- SUBUNIT: Interacts with DICER1 through its Piwi domain and with CC TARBP2 during assembly of the RNA-induced silencing complex CC (RISC). Together, DICER1, EIF2C2/AGO2 and TARBP2 constitute the CC trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading CC complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are CC required to process precursor miRNAs (pre-miRNAs) to mature miRNAs CC and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the CC mature miRNA constitutes the minimal RISC and may subsequently CC dissociate from DICER1 and TARBP2. Note however that the term RISC CC has also been used to describe the trimeric RLC/miRLC. The CC formation of RISC complexes containing siRNAs rather than miRNAs CC appears to occur independently of DICER1. Interacts with CC EIF2C1/AGO1. Also interacts with DDB1, DDX6, DDX20, DDX47, DHX9, CC DHX36, EIF6, FXR1, GEMIN4, ILF3, MOV10, PRMT5, P4HA1, P4HB, SART3, CC TNRC6A, TNRC6B and UPF1. Interacts with the P-body components CC DCP1A and XRN1 (By similarity). 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 -!- 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 -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily. CC -!- SIMILARITY: Contains 1 PAZ domain. CC -!- SIMILARITY: Contains 1 Piwi domain. CC -!- CAUTION: Was originally (PubMed:10512872) thought to be membrane- CC associated. 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; AF195534; AAF12800.1; ALT_INIT; mRNA. DR IPI; IPI00214529; -. DR RefSeq; NP_067608.1; -. DR UniGene; Rn.35512; -. DR SMR; Q9QZ81; 223-390. DR STRING; Q9QZ81; -. DR Ensembl; ENSRNOT00000011898; ENSRNOP00000011898; ENSRNOG00000008533; Rattus norvegicus. DR GeneID; 59117; -. DR KEGG; rno:59117; -. DR CTD; 59117; -. DR RGD; 621255; Eif2c2. DR HOVERGEN; Q9QZ81; -. DR NextBio; 611775; -. DR ArrayExpress; Q9QZ81; -. DR Genevestigator; Q9QZ81; -. DR GermOnline; ENSRNOG00000008533; Rattus norvegicus. 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:0016442; C:RNA-induced silencing complex; ISS:UniProtKB. DR GO; GO:0070551; F:endoribonuclease activity, cleaving siRNA-p...; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. 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; NAS:RGD. DR GO; GO:0035279; P:mRNA cleavage involved in gene silencing by...; ISS:UniProtKB. DR GO; GO:0035278; P:negative regulation of translation involved...; ISS:UniProtKB. DR GO; GO:0045947; P:negative regulation of translational initia...; ISS:UniProtKB. DR GO; GO:0031054; P:pre-microRNA processing; ISS:UniProtKB. DR GO; GO:0045449; P:regulation of transcription; IEA:UniProtKB-KW. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR InterPro; IPR014811; DUF1785. DR InterPro; IPR003100; PAZ. DR InterPro; IPR003165; Piwi. DR Pfam; PF08699; DUF1785; 1. DR Pfam; PF02170; PAZ; 1. DR Pfam; PF02171; Piwi; 1. DR PROSITE; PS50821; PAZ; 1. DR PROSITE; PS50822; PIWI; 1. PE 2: Evidence at transcript level; KW Cytoplasm; Endonuclease; Hydrolase; Hydroxylation; Metal-binding; KW Nitration; Nuclease; Nucleus; 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_0000194060. FT DOMAIN 236 349 PAZ. FT DOMAIN 518 819 Piwi. FT METAL 598 598 Divalent cation (By similarity). FT METAL 670 670 Divalent cation (By similarity). FT METAL 808 808 Divalent cation (By similarity). FT MOD_RES 2 2 Nitrated tyrosine (By similarity). FT MOD_RES 701 701 4-hydroxyproline (By similarity). SQ SEQUENCE 860 AA; 97318 MW; A5B0798C66481C9C 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 ACIKLEKEYQ PGITFIVVQK RHHTRLFCTD KNERVGKSGN IPAGTTVDTK ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL QILTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA //