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HAMAP rule MF_03031

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General rule information [?]

Accession MF_03031
Dates 14-APR-2009 (Created)
17-JAN-2024 (Last updated, Version 23)
Name AGO2
Scope(s) Eukaryota
Vertebrata
Template(s) Q9UKV8 (AGO2_HUMAN); Q8CJG0 (AGO2_MOUSE); [ Recover all ]
Triggered by HAMAP; MF_03031 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier AGO2
Protein name RecName: Full=Protein argonaute-2;
                 Short=Argonaute2;
                 EC=3.1.26.n2;
AltName: Full=Eukaryotic translation initiation factor 2C 2;
                 Short=eIF-2C 2;
                 Short=eIF2C 2;
AltName: Full=Protein slicer;
Gene name Name=AGO2; Synonyms=EIF2C2;

Comments [?]

case <OC:Mammalia>
FUNCTIONRequired for RNA-mediated gene silencing (RNAi) by the RNA- induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7- methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P- bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up- regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF- alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions.
else case <OC:Vertebrata> and not <OC:Mammalia>
FUNCTIONRequired for RNA-mediated gene silencing (RNAi) by the RNA- induced silencing complex (RISC). The 'minimal RISC' appears to include ago2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by ago2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P- bodies), where mRNA degradation may subsequently occur.
end case
CATALYTIC ACTIVITY Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.n2;
case <OC:Mammalia>
SUBUNITInteracts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1. Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA-and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA. Interacts with TRIM71. Interacts with APOBEC3G in an RNA- dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36.
else case <OC:Vertebrata> and not <OC:Mammalia>
SUBUNITComponent of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of dicer1, ago2 and tarbp2. Note that the trimeric RLC/miRLC is also referred to as RISC.
end case
case <OC:Mammalia>
SUBCELLULAR LOCATIONCytoplasm, P-body. Nucleus. Note=Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.
else case <OC:Vertebrata> and not <OC:Mammalia>
SUBCELLULAR LOCATIONCytoplasm, P-body.
end case
DOMAINThe Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp- Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).
case <OC:Mammalia>
PTMHydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.
end case
SIMILARITYBelongs to the argonaute family. Ago subfamily.

Keywords [?]

Cytoplasm
Endonuclease
Hydrolase
Metal-binding
Nuclease
Ribonucleoprotein
RNA-binding
RNA-mediated gene silencing
Translation regulation
case <FTTag:hydroxy>
Hydroxylation
end case
case <FTTag:nitro>
Nitration
end case
case <OC:Mammalia>
Nucleus
Repressor
Transcription
Transcription regulation
end case

Gene Ontology [?]

GO:0000340; Molecular function:RNA 7-methylguanosine cap binding
GO:0016891; Molecular function:RNA endonuclease activity, producing 5'-phosphomonoesters
GO:0035197; Molecular function:siRNA binding
GO:0035198; Molecular function:miRNA binding
GO:0098808; Molecular function:mRNA cap binding
GO:0031054; Biological process:pre-miRNA processing
GO:0035278; Biological process:miRNA-mediated gene silencing by inhibition of translation
GO:0035279; Biological process:miRNA-mediated gene silencing by mRNA destabilization
GO:0045947; Biological process:negative regulation of translational initiation
GO:0016442; Cellular component:RISC complex

Cross-references [?]

PROSITE PS50821; PAZ; 1;
PROSITE PS50822; PIWI; 1;
Pfam PF08699; DUF1785; 1;
Pfam PF02170; PAZ; 1;
Pfam PF02171; Piwi; 1;

Features [?]

From: AGO2_HUMAN (Q9UKV8)
Key From To Description Tag Condition FTGroup
case <OC:Vertebrata>
BINDING 597 597 /ligand="a divalent metal cation"
/ligand_id="ChEBI:CHEBI:60240"		 D
BINDING 669 669 /ligand="a divalent metal cation"
/ligand_id="ChEBI:CHEBI:60240"		 D
BINDING 807 807 /ligand="a divalent metal cation"
/ligand_id="ChEBI:CHEBI:60240"		 H
end case
case <OC:Mammalia>
MOD_RES 2 2 /note="3'-nitrotyrosine" nitro Y
MOD_RES 700 700 /note="4-hydroxyproline" hydroxy P
end case

Additional information [?]

Size range 859-871 amino acids
Related rules None
Fusion Nter: None Cter: None



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