AC MF_03031; DC Protein; auto TR HAMAP; MF_03031; -; 1; level=0 XX Names: AGO2 XX ID AGO2 DE RecName: Full=Protein argonaute-2; DE Short=Argonaute2; 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=Protein slicer; GN Name=AGO2; Synonyms=EIF2C2; XX case 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. else case and not 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. 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. end case CC -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; CC EC=3.1.26.n2; case 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. Interacts with AGO1. Also interacts with DDB1, CC DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, CC HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, CC SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body CC components DCP1A and XRN1. Associates with polysomes and messenger CC ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is CC modulated under stress-induced conditions, occurs under both cell CC proliferation and differentiation conditions and in an RNA-and CC phosphorylation-independent manner. Interacts with LIMD1, WTIP and CC AJUBA. Interacts with TRIM71. 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. else case and not CC -!- SUBUNIT: Component of the RISC loading complex (RLC), or micro-RNA CC (miRNA) loading complex (miRLC), which is composed of dicer1, ago2 and CC tarbp2. Note that the trimeric RLC/miRLC is also referred to as RISC. end case case CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body. Nucleus. Note=Translational CC repression of mRNAs results in their recruitment to P-bodies. CC Translocation to the nucleus requires IMP8. else case and not CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body. end case 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). case CC -!- PTM: Hydroxylated. 4-hydroxylation appears to enhance protein stability CC but is not required for miRNA-binding or endonuclease activity. end case CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily. XX DR PROSITE; PS50821; PAZ; 1; trigger=yes DR PROSITE; PS50822; PIWI; 1; trigger=yes DR Pfam; PF08699; DUF1785; 1; trigger=no DR Pfam; PF02170; PAZ; 1; trigger=no DR Pfam; PF02171; Piwi; 1; trigger=no XX KW Cytoplasm KW Endonuclease KW Hydrolase KW Metal-binding KW Nuclease KW Ribonucleoprotein KW RNA-binding KW RNA-mediated gene silencing KW Translation regulation case KW Hydroxylation end case case KW Nitration end case case KW Nucleus KW Repressor KW Transcription KW Transcription regulation end case XX GO GO:0000340; F:RNA 7-methylguanosine cap binding GO GO:0016891; F:RNA endonuclease activity, producing 5'-phosphomonoesters GO GO:0035197; F:siRNA binding GO GO:0035198; F:miRNA binding GO GO:0098808; F:mRNA cap binding GO GO:0031054; P:pre-miRNA processing GO GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation GO GO:0035279; P:miRNA-mediated gene silencing by mRNA destabilization GO GO:0045947; P:negative regulation of translational initiation GO GO:0016442; C:RISC complex XX FT From: AGO2_HUMAN (Q9UKV8) case FT BINDING 597 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT Condition: D FT BINDING 669 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT Condition: D FT BINDING 807 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT Condition: H end case case FT MOD_RES 2 FT /note="3'-nitrotyrosine" FT Tag: nitro; Condition: Y FT MOD_RES 700 FT /note="4-hydroxyproline" FT Tag: hydroxy; Condition: P end case XX Size: 859-871; Related: None; Template: Q9UKV8; Q8CJG0; Scope: Eukaryota; Vertebrata Fusion: Nter: None Cter: None Duplicate: None Plasmid: None Comments: None XX # Revision 1.23 2024/01/17 //