AGO2

Summary: AGO2 supports nucleus in the specified molecular or cellular context.

Reason: AGO2 has an experimentally supported nuclear pool, including human-cell nuclear RNA targeting and promoter-associated regulation. This is retained as a contextual compartment alongside its major cytoplasmic silencing roles (PMID:19167051; PMID:23985560; PMID:25336585).

Summary: AGO2 supports cytoplasm in the specified molecular or cellular context.

Reason: Cytoplasmic AGO2-containing RNA complexes execute post-transcriptional silencing. The broad compartment is valid at the source resolution, even though particular AGO2 pools also occupy granules or membranes (PMID:17932509; PMID:19801630).

Summary: AGO2 supports RNA endonuclease activity in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports regulatory ncRNA-mediated post-transcriptional gene silencing in the specified molecular or cellular context.

Reason: AGO2 carries out regulatory-RNA-directed silencing by binding a guide, recognizing its RNA target, and either cleaving sufficiently paired targets or recruiting silencing effectors. These are direct contributions rather than a downstream phenotype alone (PMID:15260970; PMID:19324964).

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports cytoplasmic ribonucleoprotein granule in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: AGO2 participates in precursor conversion; the precise ancestral processing mechanism remains unresolved.

Reason: The cached PAINT IBD places GO:0031054 at PTN000527278, with AGO2 itself among the legitimate experimental descendant sources. Human HEK293F extract assays in PMID:17671087 Figure 1 show increased pre-let-7 conversion after AGO2 overexpression; the same Results report an AGO1 effect without displaying those data. These findings support a processing contribution without equating every Argonaute mechanism. Independent primary evidence establishes direct human AGO2 precursor cleavage: recombinant hAGO2 cleaved the short pre-miR-451 hairpin to a 30-nt intermediate in PMID:20448148 Figure 2B. Subsequent 3-prime trimming is a separate step. This substrate-specific reaction is distinct from Dicer cleavage of canonical pre-miRNAs and from guide loading. The target assertion is accepted, while the exact molecular contribution ancestral to all descendants is not independently reconstructed; AGO2-specific slicing alone does not validate that ancestral mechanism.

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796).

Summary: AGO2 supports single-stranded RNA binding in the specified molecular or cellular context.

Reason: AGO2 retains a single-stranded guide after duplex unwinding and also engages target RNA. This broad binding state is experimentally meaningful and is not replaced by miRNA specificity alone (PMID:19966796; PMID:15260970).

Summary: AGO2 association with cap-containing complexes is established; intrinsic cap recognition remains disputed.

Reason: PMID:17524464 proposed intrinsic MID-domain cap recognition. PMID:19159466 challenges the motif structurally, and PMID:21475248 found no selective cap binding by the isolated MID domain or active recombinant AGO2 lacking its N-terminal proline-rich segment. In contrast, PMID:23409027 shows cap photocrosslinking/proximity in cellular AGO2 complexes enhanced by eIF4GI. These assay contexts do not resolve whether AGO2 itself selectively recognizes the cap or is positioned there by cofactors. Direct cap-binding activity remains UNDECIDED; translation repression is independently retained.

Summary: AGO2 supports P-body in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: AGO2 supports nucleic acid binding in the specified molecular or cellular context.

Reason: AGO2 directly binds small guide RNAs and their RNA targets. The broad source-level binding term is correct; a generic nucleic-acid label does not assert DNA binding, and an RNA-interactome assay need not resolve the guide/target distinction (PMID:15260970; PMID:19167051).

Summary: AGO2 supports RNA binding in the specified molecular or cellular context.

Reason: AGO2 directly binds small guide RNAs and their RNA targets. The broad source-level binding term is correct; a generic nucleic-acid label does not assert DNA binding, and an RNA-interactome assay need not resolve the guide/target distinction (PMID:15260970; PMID:19167051).

Summary: AGO2 supports double-stranded RNA binding in the specified molecular or cellular context.

Reason: Human AGO2 accepts small-RNA duplexes during pre-RISC assembly before passenger-strand removal. Duplex binding is a supported loading state; it does not imply nonspecific recognition of all long dsRNA (PMID:19966796).

Summary: AGO2 supports single-stranded RNA binding in the specified molecular or cellular context.

Reason: AGO2 retains a single-stranded guide after duplex unwinding and also engages target RNA. This broad binding state is experimentally meaningful and is not replaced by miRNA specificity alone (PMID:19966796; PMID:15260970).

Summary: AGO2 supports nucleus in the specified molecular or cellular context.

Reason: AGO2 has an experimentally supported nuclear pool, including human-cell nuclear RNA targeting and promoter-associated regulation. This is retained as a contextual compartment alongside its major cytoplasmic silencing roles (PMID:19167051; PMID:23985560; PMID:25336585).

Summary: AGO2 supports regulation of DNA-templated transcription in the specified molecular or cellular context.

Reason: Nuclear AGO2 participates in RNA-guided transcriptional regulation in the reported senescence and promoter contexts. The InterPro family inference is corroborated by human experiments, but it does not establish AGO2 as a general sequence-specific DNA transcription factor (PMID:22366686; PMID:25336585).

Summary: The legacy translation/initiation assertion needs its original mechanistic support resolved.

Reason: The cached abstract explicitly concerns cloning human EIF2C1 on chromosome 1 and comparison with rabbit eIF2C. PubMed identity was independently checked. Full text was not recovered, so it does not establish whether AGO2 or a transferable initiation mechanism was examined; the legacy NAS assertions remain unresolved rather than being declared a naming error. The formal initiation-factor definition is broad, and AGO2 can promote translation in specific contexts; modern nomenclature or its predominant repressor role does not establish that this historical assertion is false.

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports RNA endonuclease activity producing 5'-phosphomonoesters, hydrolytic mechanism in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports regulatory ncRNA-mediated gene silencing in the specified molecular or cellular context.

Reason: AGO2 carries out regulatory-RNA-directed silencing by binding a guide, recognizing its RNA target, and either cleaving sufficiently paired targets or recruiting silencing effectors. These are direct contributions rather than a downstream phenotype alone (PMID:15260970; PMID:19324964).

Summary: Independent human and mouse evidence supports AGO2-dependent precursor processing.

Reason: Independent primary evidence establishes direct human AGO2 precursor cleavage: recombinant hAGO2 cleaved the short pre-miR-451 hairpin to a 30-nt intermediate in PMID:20448148 Figure 2B. Subsequent 3-prime trimming is a separate step. This substrate-specific reaction is distinct from Dicer cleavage of canonical pre-miRNAs and from guide loading. Mouse catalytically inactive Ago2 experiments in PMID:20424607 independently link precursor processing to Ago2 catalysis. The rodent and human results support the biological target judgment; the unrecovered ARBA and UniRule condition sets are not represented as validated.

Summary: AGO2 supports siRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds siRNA guides that specify RNA targets for RISC. The activity is directly established for human AGO2; partner enzymes that generate or phosphorylate the guide are not being assigned to AGO2 (PMID:15260970; PMID:15973356).

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796).

Summary: AGO2 supports miRNA-mediated gene silencing by inhibition of translation in the specified molecular or cellular context.

Reason: Guide-loaded AGO2 recruits miRISC effectors that inhibit target translation, including initiation-stage repression in the reported contexts. This belongs to its core silencing role. Uncertainty about intrinsic cap recognition does not negate repression, nor does AGO2 independently perform all downstream effector reactions (PMID:19324964; PMID:18771919).

Summary: AGO2 supports miRNA-mediated gene silencing by mRNA destabilization in the specified molecular or cellular context.

Reason: AGO2 executes guide-dependent target endonucleolysis. The formal GO term describes cleavage-mediated destabilization; AGO2 also recruits nonnucleolytic decay machinery, which is a separate mechanism and is not the sole basis for this annotation (PMID:15260970; PMID:18771919).

Summary: AGO2 supports cytoplasmic ribonucleoprotein granule in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: AGO2 supports negative regulation of translational initiation in the specified molecular or cellular context.

Reason: Guide-loaded AGO2 recruits miRISC effectors that inhibit target translation, including initiation-stage repression in the reported contexts. This belongs to its core silencing role. Uncertainty about intrinsic cap recognition does not negate repression, nor does AGO2 independently perform all downstream effector reactions (PMID:19324964; PMID:18771919).

Summary: AGO2 supports endoribonuclease activity, cleaving siRNA-paired mRNA in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports RISC complex assembly in the specified molecular or cellular context.

Reason: AGO2 participates directly in RISC assembly by accepting a duplex, retaining a guide, and releasing or cleaving its passenger strand. It is an executing component of the assembly pathway, not merely a substrate whose abundance changes (PMID:19966796).

Summary: AGO2 association with cap-containing complexes is established; intrinsic cap recognition remains disputed.

Reason: PMID:17524464 proposed intrinsic MID-domain cap recognition. PMID:19159466 challenges the motif structurally, and PMID:21475248 found no selective cap binding by the isolated MID domain or active recombinant AGO2 lacking its N-terminal proline-rich segment. In contrast, PMID:23409027 shows cap photocrosslinking/proximity in cellular AGO2 complexes enhanced by eIF4GI. These assay contexts do not resolve whether AGO2 itself selectively recognizes the cap or is positioned there by cofactors. Direct cap-binding activity remains UNDECIDED; translation repression is independently retained.

Summary: GST–AGO2 binds Dicer and inhibits its endoribonuclease activity in vitro.

Reason: The full original Results/Figures 3–4 show purified-protein association, nuclease-resistant binding, PIWI-box/RNaseIII-A interaction, and dose-dependent inhibition of Dicer cleavage by GST–AGO2 compared with GST. These findings support the more informative endoribonuclease-inhibitor activity at the recombinant in-vitro scope. The study did not isolate substrate sequestration from contact-mediated inhibition, and physiological inhibition was left unresolved; this activity is excluded from core functions (PMID:14749716).

Proposed replacements: endoribonuclease inhibitor activity

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source identifies PACT interactions with Dicer and AGO2 and impaired miRNA accumulation after PACT depletion. It supports AGO2 participation in the miRNA-processing complex, not independent AGO2 RNaseIII cleavage of every canonical precursor. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source describes RCK/p54 interactions with human Argonautes and miRISC-mediated repression. P-body disruption and repression can be separated experimentally, so granule localization does not establish that a visible P-body is obligatory for every AGO2 silencing event. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The cached abstract concerns LRRK2 immunoprecipitation and candidate interactors. The exact AGO2 interaction experiment was not recovered. Removal of the generic binding term does not claim that the recorded pair is false or that a title centered on LRRK2 excludes AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract links GW repeats to Argonaute recognition across fission-yeast and human systems. Conserved docking motifs do not by themselves establish that human AGO2 has the full fission-yeast RITS complex role. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source separates human AGO1/AGO2 mRNPs into three complexes with distinct Dicer and RISC activities and maps RNase-sensitive interactions. The curated cytoplasm and RISC assertions are biologically consistent; proteomic association does not define a separate generic binding core. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The primary abstract describes reconstitution of human RISC with one copy each of Dicer, TRBP and AGO2, coupling guide processing/loading to slicing and subsequent AGO2 dissociation. This is direct support for the defined trimeric RISC-loading complex and AGO2 catalytic contribution. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract describes IMP8 interaction with Argonautes, reduced nuclear AGO2 after IMP8 depletion in HeLa cells and a role in targeting AGO2 to mRNAs. Nuclear localization and target recruitment are distinct from a claim that AGO2 itself is an import receptor. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source maps AGO2 interaction with GW182 and shows GW182 dependence of tethered AGO2 repression. It supports effector recruitment rather than assigning GW182 downstream effector chemistry to AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source compares human TNRC6 family members, their Argonaute-binding regions and silencing domains. AGO2 recruitment is distinct from the autonomous activity of tethered TNRC6 silencing domains. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source connects GW182/PABP/CAF1 to miRNA-mediated deadenylation, including mouse extract experiments. CAF1 performs poly(A) hydrolysis; AGO2 supplies guide-directed targeting and effector recruitment. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full structural study reconstructs the human Dicer–TRBP–AGO2 loading complex by electron microscopy. It supports the defined RLC and guide engagement, not an assertion that every AGO2-containing precursor RNP has this exact composition. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full paper uses human AGO constructs in mouse NIH3T3 cells with tethering and transcriptional pulse-chase. AGO–TNRC6 recruitment accelerates PAN2–PAN3 then CCR4–CAF1 deadenylation and decapping-dependent decay. F470/F505 mutants impair TNRC6 recruitment, so their repression defect is not a unique diagnostic of cap binding. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source concerns CRM1-dependent nuclear trafficking of AGO-containing complexes with transcription/chromatin regulators. Coassociation does not assign CRM1 export-receptor function or partner catalytic activities to AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract explicitly distinguishes Drosophila Ago1 and human AGO2 interactions with LRRK2. The partner and organism differences are not evidence of a misattributed human AGO2 interaction. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source connects RACK1 to ribosome-associated miRISC and includes human and nematode experiments. Ribosomal recruitment does not establish that AGO2 is a ribosomal structural protein or canonical translation initiation factor. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The study concerns translation/NMD-related AGO2 interactions and cap-motif mutants. Effects of F470/F505 substitutions are not uniquely diagnostic of direct cap recognition, given independent evidence for impaired TNRC6 recruitment. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The cached abstract foregrounds nuclear Dicer and NUP153. The exact AGO2 interaction was not recovered, so no wrong-gene assertion is made. Generic protein binding remains uninformative even though pair-level support is unresolved. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: This is an innate-immunity interaction-network source. The available cache is limited and does not establish a specific AGO2 molecular mechanism. A network edge is not treated as direct binding or intrinsic immune enzymatic activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source establishes GW182-mediated recruitment of PAN3 and NOT1/CCR4–NOT. AGO2 is the upstream guide-binding effector, not the poly(A) nuclease or all contacts made by GW182. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full primary paper supports AGO2/let-7 involvement in senescence-associated transcriptional silencing with RB1. This is a context-specific nuclear regulatory role, not a claim that AGO2 is a general DNA-dependent transcription factor. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes prion-protein GW-motif interaction with AGO/TNRC6 and endosomal miRISC assembly. It does not imply that AGO2 acquires the partner transmembrane topology. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes WIG1-facilitated recruitment of AGO2 to a structured p21 mRNA target. RNA target recognition and partner recruitment do not establish that AGO2 performs WIG1 zinc-finger functions. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source concerns GW182 regulation of miRNA stability and extracellular release. Association with AGO2 does not assign the downstream degradation or vesicle-export machinery to AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source characterizes an ADAR1–Dicer complex promoting miRNA processing. AGO2 association does not assign ADAR1 RNA editing or Dicer RNaseIII chemistry to AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract reports hypoxia/EGFR-dependent AGO2 Y393 phosphorylation and altered Dicer association. This is regulation of AGO2-containing processing complexes, not AGO2 receptor-kinase activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full primary source reconstitutes human Dicer–TRBP–AGO2 and Dicer–PACT–AGO2 complexes and measures precursor processing/isomiR differences. AGO2 participates as a loading-complex component; Dicer remains the RNaseIII catalyst and TRBP/PACT modulate substrate handling. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes chaperone interactions with unloaded AGO2, including HSP90, p23 and FKBP4. It supports loading/maturation context rather than a novel AGO2 chaperone enzyme activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The structural/biophysical source examines GW182 tryptophan motifs and AGO2 docking. The informative consequence is effector recruitment in silencing; generic protein binding does not describe that role. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source concerns a TERT/BRG1/nucleostemin heterochromatin network and RNA-silencing factors. Association does not assign TERT reverse transcription or BRG1 ATPase activity to AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract centers on MTDH/SND1 in tumor models. Exact AGO2 pair evidence was not independently recovered; no misattribution is inferred from the foregrounded proteins. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: PubMed links this original to the 2025 Expression of Concern PMID:40930611, DOI 10.1016/j.ccell.2025.07.022. The full notice was read at the MD Anderson ElsevierPure institutional record on 2026-09-27. It reports an institutional investigation of duplicated/relabelled Dicer, CD9, tRNA, miRNA, flotillin and TSG101 panels and a recommendation for retraction, disputed by some authors, with journal review ongoing. This is an Expression of Concern, not a retraction or proof that a particular AGO2 pair is false. Independent exosomal AGO2 evidence is assessed separately. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: This is a large human-cell affinity-purification/mass-spectrometry interaction map. Co-complex recovery does not establish direct binary binding or a unique mechanism for each AGO2 network edge. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source identifies LIMD1 as a phospho-AGO2/TNRC6 adaptor, including simultaneous binding and S387-dependent effects. Those data identify LIMD1 adaptor activity and AGO2 recruitment, not a generic AGO2 adaptor assignment. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes PLEKHA7 recruitment of AGO2/GW182/PABPC1 and associated RNAs to adherens junctions. Junctional RNP assembly is distinct from direct binding by every recovered pair. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: This is a neurodegeneration-focused cellular interaction map, with full primary material available in the campaign. A reported AGO2 edge is retained as provenance, not converted into direct binding or a new catalytic role. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The BioPlex interaction-network source compares human cellular contexts. The cache is incomplete; affinity-purification associations do not alone establish direct binary affinity or the mechanism of AGO2 in every partner pathway. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: OpenCell combines endogenous tagging, imaging and interaction measurements. The cache provides limited primary sections. A protein-network association is not interpreted as a unique AGO2 molecular activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source integrates RNA-binding-protein proximity/interaction and functional data. A network edge does not establish direct binary AGO2 binding, and activities of neighboring RNA enzymes are not transferred to AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports mRNA binding in the specified molecular or cellular context.

Reason: The mouse Ago2 orthology inference is consistent with human AGO2-associated target mRNAs and guide-dependent recognition. Target-mRNA binding is not interchangeable with miRNA-guide binding (PMID:19167051).

Summary: AGO2 supports RNA endonuclease activity in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports cytosol in the specified molecular or cellular context.

Reason: Cytoplasmic AGO2-containing RNA complexes execute post-transcriptional silencing. The broad compartment is valid at the source resolution, even though particular AGO2 pools also occupy granules or membranes (PMID:17932509; PMID:19801630).

Summary: AGO2 supports dendrite in the specified molecular or cellular context.

Reason: The inferred mouse Ago2 dendritic localization is consistent with experiments expressing human AGO2 constructs in rat hippocampal neurons. Dendritic/synaptic regulation is a contextual deployment of its RNA-regulatory activity (PMID:29735530).

Summary: AGO2 supports positive regulation of nuclear-transcribed mRNA poly(A) tail shortening in the specified molecular or cellular context.

Reason: AGO2 promotes poly(A)-tail shortening and subsequent decay through TNRC6-dependent effector recruitment. Human AGO tethering and pulse-chase experiments in mouse NIH3T3 cells directly show this contribution. PAN2–PAN3 and CCR4–CAF1 catalyze the hydrolysis, while AGO2 targets and recruits the machinery; the regulatory process is therefore core (PMID:19838187).

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710).

Summary: AGO2 supports positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay in the specified molecular or cellular context.

Reason: AGO2 promotes poly(A)-tail shortening and subsequent decay through TNRC6-dependent effector recruitment. Human AGO tethering and pulse-chase experiments in mouse NIH3T3 cells directly show this contribution. PAN2–PAN3 and CCR4–CAF1 catalyze the hydrolysis, while AGO2 targets and recruits the machinery; the regulatory process is therefore core (PMID:19838187).

Summary: AGO2 supports ribonucleoprotein complex in the specified molecular or cellular context.

Reason: AGO2 binds small RNAs and target RNAs in ribonucleoprotein complexes. The broad complex term correctly describes its core physical form; RISC is represented separately without invalidating the broader source assertion (PMID:17932509; PMID:15260970).

Summary: AGO2 supports miRNA processing in the specified molecular or cellular context.

Reason: AGO2 contributes to production of functional miRNA through guide loading and RISC maturation, and as part of experimentally reconstituted precursor-processing/loading complexes. Dicer performs canonical RNaseIII cleavage; AGO2 binding, guide selection and passenger removal are distinct contributions. This general maturation role is shared across human Argonautes and is not justified solely by an AGO2-specific precursor pathway (PMID:19966796; PMID:18178619; PMID:23661684). PMID:28781232 principally measures mature AGO/GW182 recruitment rather than precursor cleavage; the functional maturation judgment is independently grounded in PMID:19966796 and PMID:18178619.

Summary: AGO2 supports regulatory ncRNA-mediated post-transcriptional gene silencing in the specified molecular or cellular context.

Reason: AGO2 carries out regulatory-RNA-directed silencing by binding a guide, recognizing its RNA target, and either cleaving sufficiently paired targets or recruiting silencing effectors. These are direct contributions rather than a downstream phenotype alone (PMID:15260970; PMID:19324964).

Summary: AGO2 supports cytoplasmic ribonucleoprotein granule in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: AGO2 supports RNA endonuclease activity in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports regulation of synapse maturation in the specified molecular or cellular context.

Reason: The full primary Methods identify human GFP–AGO2 WT/S387A/S387D expressed in rat hippocampal neurons. Spine localization, PSD95 measurements and phosphomutant effects on spine density/maturation support the annotated synaptic context. This is a non-core neuronal role, not a claim of endogenous human-neuron measurement (PMID:29735530, externally read PMC6005451).

Summary: AGO2 supports regulation of synapse maturation in the specified molecular or cellular context.

Reason: The full primary Methods identify human GFP–AGO2 WT/S387A/S387D expressed in rat hippocampal neurons. Spine localization, PSD95 measurements and phosphomutant effects on spine density/maturation support the annotated synaptic context. This is a non-core neuronal role, not a claim of endogenous human-neuron measurement (PMID:29735530, externally read PMC6005451).

Summary: AGO2 supports postsynapse in the specified molecular or cellular context.

Reason: The full primary Methods identify human GFP–AGO2 WT/S387A/S387D expressed in rat hippocampal neurons. Spine localization, PSD95 measurements and phosphomutant effects on spine density/maturation support the annotated synaptic context. This is a non-core neuronal role, not a claim of endogenous human-neuron measurement (PMID:29735530, externally read PMC6005451).

Summary: AGO2 supports postsynapse in the specified molecular or cellular context.

Reason: The full primary Methods identify human GFP–AGO2 WT/S387A/S387D expressed in rat hippocampal neurons. Spine localization, PSD95 measurements and phosphomutant effects on spine density/maturation support the annotated synaptic context. This is a non-core neuronal role, not a claim of endogenous human-neuron measurement (PMID:29735530, externally read PMC6005451).

Summary: AGO2 supports glutamatergic synapse in the specified molecular or cellular context.

Reason: The full primary Methods identify human GFP–AGO2 WT/S387A/S387D expressed in rat hippocampal neurons. Spine localization, PSD95 measurements and phosphomutant effects on spine density/maturation support the annotated synaptic context. This is a non-core neuronal role, not a claim of endogenous human-neuron measurement (PMID:29735530, externally read PMC6005451).

Summary: AGO2 supports glutamatergic synapse in the specified molecular or cellular context.

Reason: The full primary Methods identify human GFP–AGO2 WT/S387A/S387D expressed in rat hippocampal neurons. Spine localization, PSD95 measurements and phosphomutant effects on spine density/maturation support the annotated synaptic context. This is a non-core neuronal role, not a claim of endogenous human-neuron measurement (PMID:29735530, externally read PMC6005451).

Summary: AGO2 association with cap-containing complexes is established; intrinsic cap recognition remains disputed.

Reason: PMID:17524464 proposed intrinsic MID-domain cap recognition. PMID:19159466 challenges the motif structurally, and PMID:21475248 found no selective cap binding by the isolated MID domain or active recombinant AGO2 lacking its N-terminal proline-rich segment. In contrast, PMID:23409027 shows cap photocrosslinking/proximity in cellular AGO2 complexes enhanced by eIF4GI. These assay contexts do not resolve whether AGO2 itself selectively recognizes the cap or is positioned there by cofactors. Direct cap-binding activity remains UNDECIDED; translation repression is independently retained.

Summary: AGO2 supports cytoplasm in the specified molecular or cellular context.

Reason: Cytoplasmic AGO2-containing RNA complexes execute post-transcriptional silencing. The broad compartment is valid at the source resolution, even though particular AGO2 pools also occupy granules or membranes (PMID:17932509; PMID:19801630).

Summary: The curated P-body assembly assignment requires clarification of AGO2's executing step.

Reason: The abstract-only cache was supplemented by externally read PMC6755100 Results/Figures 3–5 and 8. AGO2 depletion did not reduce visible P-body counts in the tested cells, whereas GW182/DDX6 depletion did; AGO2 also localized to granules. This is evidence against AGO2 being necessary for the measured assembly endpoint, not a direct demonstration that AGO2 never participates in assembly. GO-CAM 653b0ce600001283 explicitly assigns AGO2 to GO:0033962 with IDA from this paper. The UNDECIDED judgment defers to that curated source assertion pending identification of the specific assembly action, as raised in suggested_questions. Granule occupancy alone does not establish assembly, and no redundant mechanism is assumed.

Summary: AGO2 selectively associates with the TNF-alpha AU-rich 3′-UTR RNP during serum starvation.

Reason: The full primary Results show ARE-specific complex recovery and AGO2 RNA co-IP, with control reporters and serum conditions. This supports the curator’s context-specific RNA-association judgment. Formaldehyde crosslinking can preserve indirect contacts, so the result is not described as purified, guide-independent recognition of an AU motif by AGO2 alone (PMID:17382880, externally read PMC3430382 Figures 3–5).

Summary: AGO2 and FXR1 promote translation in serum-starved human cells.

Reason: Tethering, depletion and interdependence experiments support AGO2 participation in ARE-associated translation activation under cell-cycle arrest. The positive role is conditional and coexists with its predominant repressive RISC role (PMID:17382880).

Summary: AGO2 supports nucleoplasm in the specified molecular or cellular context.

Reason: The Reactome source places AGO2 in a nuclear transport or nuclear RNP context. Independent human HeLa-cell localization and nuclear RNA regulation corroborate the nuclear pool; these data do not require direct AGO2 recognition of promoter DNA (PMID:19167051; PMID:23985560).

Summary: AGO2 supports nucleoplasm in the specified molecular or cellular context.

Reason: The Reactome source places AGO2 in a nuclear transport or nuclear RNP context. Independent human HeLa-cell localization and nuclear RNA regulation corroborate the nuclear pool; these data do not require direct AGO2 recognition of promoter DNA (PMID:19167051; PMID:23985560).

Summary: AGO2 supports nucleoplasm in the specified molecular or cellular context.

Reason: The Reactome source places AGO2 in a nuclear transport or nuclear RNP context. Independent human HeLa-cell localization and nuclear RNA regulation corroborate the nuclear pool; these data do not require direct AGO2 recognition of promoter DNA (PMID:19167051; PMID:23985560).

Summary: AGO2 supports miRNA-mediated gene silencing by inhibition of translation in the specified molecular or cellular context.

Reason: Guide-loaded AGO2 recruits miRISC effectors that inhibit target translation, including initiation-stage repression in the reported contexts. This belongs to its core silencing role. Uncertainty about intrinsic cap recognition does not negate repression, nor does AGO2 independently perform all downstream effector reactions (PMID:19324964; PMID:18771919).

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619). PMID:19701182 Figure 5c identifies AGO2-associated RMRP-derived small RNA; its TERT–RMRP polymerase activity is not assigned to AGO2.

Summary: AGO2 supports RISC complex assembly in the specified molecular or cellular context.

Reason: AGO2 participates directly in RISC assembly by accepting a duplex, retaining a guide, and releasing or cleaving its passenger strand. It is an executing component of the assembly pathway, not merely a substrate whose abundance changes (PMID:19966796). In PMID:19701182 Figure 5c, association of processed RMRP small RNA with AGO2 supports guide incorporation. The distinct TERT–RMRP RNA polymerase is upstream.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: This BioID source maps cellular proximity networks. Proximity labeling cannot by itself establish direct binary AGO2 binding or a partner-derived molecular activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619). PMID:31507089 additionally supports an AGO2-containing IL6/miR-206 RNP in human lung-cancer cells.

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796). PMID:31507089 Figure 4 RNA-ChIP supports the miR-206/IL6 targeting context, without claiming exclusivity for that guide.

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619). PMID:31012336 uses AGO2 RNA-IP in the miR-31/IL34 pathway in human tumor-cell models.

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796). The original PMID:31012336 RNP experiments are consistent with miR-31-containing AGO2 complexes, without making AGO2 uniquely selective for miR-31.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The cached abstract concerns Clnk and TNF-associated necroptosis in murine L929 cells. Exact AGO2 interaction support was not recovered; absence from the abstract is not evidence of a false interaction. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619). PMID:19826008 purifies miR-210-loaded RISC with associated target mRNAs, supporting the complex assignment.

Summary: AGO2 supports nucleus in the specified molecular or cellular context.

Reason: AGO2 has an experimentally supported nuclear pool, including human-cell nuclear RNA targeting and promoter-associated regulation. This is retained as a contextual compartment alongside its major cytoplasmic silencing roles (PMID:19167051; PMID:23985560; PMID:25336585).

Summary: AGO2 can contribute to FMRP-dependent repression of APP synthesis.

Reason: The ISS donor is rat Ago2 (UniProtKB:Q9QZ81), not mouse. The complete rat donor annotation chain was not recovered. Independent human BE2-M17 experiments in PMID:20473314 Figure 6 show APP RNA association with HA–AGO2 and FMRP-dependent repression after AGO2 overexpression. This supports contextual target-specific regulation; it is not a core APP-processing enzyme activity.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes MOV10/UPF1-associated post-transcriptional regulation. MOV10 helicase activity and AGO2 guide-directed effector function are separate molecular contributions. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1606561 (MIR449 microRNAs bind 3'UTR of NOTCH1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1606682 (MIR34 microRNAs bind 3'UTR of NOTCH1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912362 (MIR150 microRNA binds 3'UTR of NOTCH3 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912363 (MIR200B/C microRNAs bind NOTCH1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912364 (MIR181C microRNA binds 3'UTR of NOTCH4 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912366 (MIR206 microRNA binds 3'UTR of NOTCH3 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912367 (MIR34 microRNAs bind 3'UTR of NOTCH2 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912368 (MIR302A microRNA binds 3'UTR of NOTCH4 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-1912406 (p53 positively regulates transcription of MIR34 microRNAs) supplies the original compartment assertion. The summary describes p53-dependent MIR34 transcription, an upstream event, and explicitly omits processing/loading steps. It is not a direct assay of AGO2 localization or transcription-factor activity. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-203862 (Dicer cleaves pre-miRNA to yield duplex miRNA) supplies the original compartment assertion. The recovered summary explicitly identifies AGO2 as a RISC-loading complex subunit and assigns canonical precursor cleavage to DICER1. It does not export participant compartment metadata. The cytosol assertion is retained with curator deference and independent human AGO2-containing silencing-complex evidence (PMID:17932509), without treating the cached reaction summary as a localization assay.

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-2106614 (Duplex miRNA is loaded into Argonaute) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-2106615 (Removal of siRNA passenger strand) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-2106625 (Duplex siRNA is loaded into Argonaute) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-210805 (Removal of miRNA passenger strand) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-2318752 (miR-26A microRNAs bind PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-426464 (Dicer cleaves double-stranded RNA to yield double-stranded siRNA) supplies the original compartment assertion. Dicer cleaves long dsRNA in the AGO2-associated loading machinery. The summary does not make AGO2 the Dicer RNaseIII catalyst. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-426489 (RISC binds inexactly matching target RNAs) supplies the original compartment assertion. The summary distinguishes repression of imperfect targets from central-pairing-dependent AGO2 slicing and describes TNRC6/MOV10-associated silencing. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-426520 (Endonucleolytic RISC hydrolyzes target RNAs) supplies the original compartment assertion. The summary attributes guide-dependent hydrolytic target cleavage to AGO2 PIWI activity, with 5′-phosphate and 3′-hydroxyl products. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-4518575 (miR-92b binds 3'UTR of NLK mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-5578712 (Importin-8 binds AGO2:miRNA) supplies the original compartment assertion. This source concerns cytosolic AGO2–small-RNA association with importin 8 before nuclear transport and mRNA targeting. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-5578744 (Importin-8 imports AGO2:miRNA into the nucleus) supplies the original compartment assertion. The source concerns importin-8-associated nuclear transport of AGO2–small-RNA complexes. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-5578965 (TNRC6A binds AGO2:miRNA) supplies the original compartment assertion. The source describes cytosolic TNRC6A docking to AGO2 through GW motifs. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-5578966 (TNRC6A:AGO2:miRNA is transported into the nucleus) supplies the original compartment assertion. The source describes nuclear AGO2/TNRC6A complexes with incompletely resolved import machinery. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-5687103 (FOXO3 regulates MIR34B,C expression) supplies the original compartment assertion. This summary concerns FOXO3-dependent MIR34 transcription upstream of mature RISC. It is not evidence that AGO2 executes DNA-dependent transcription at this step. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8935864 (miR-302b binds RUNX1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8935930 (miR-18a binds RUNX1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8936058 (miR-675 binds RUNX1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8936068 (H19 is cleaved to produce miR-675) supplies the original compartment assertion. The source concerns production of miR-675 from H19 RNA, upstream of target silencing. AGO2 is not assumed to catalyze every precursor cleavage. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8939129 (miR-215 binds RUNX1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944483 (miR-17 microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944522 (miR-19a microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944538 (miR-22 microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944569 (miR-25 microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944599 (miR-93 microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944632 (miR-106 microRNAs bind PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8944684 (miR-205 microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8945709 (miR-20 microRNAs bind PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948524 (PTENP1 mRNA binds miR-19b RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948536 (PTENP1 mRNA binds miR-20 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948569 (miR-19b microRNA binds PTEN mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948582 (miR-17 microRNA binds VAPA mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948583 (miR-17 microRNA binds CNOT6L mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948594 (miR-19a microRNA binds VAPA mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948602 (miR-19a microRNA binds CNOT6L mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948612 (miR-19b microRNA binds CNOT6L mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948621 (miR-20 microRNAs bind VAPA mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948623 (miR-20 microRNAs bind CNOT6L mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948641 (miR-106 microRNAs bind VAPA mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-8948651 (miR-106a,(miR106b) microRNA binds CNOT6L mRNA) supplies the original compartment assertion. The title identifies CNOT6L, while a cached summary sentence names CNOT5L. This internal naming discrepancy does not determine the broad AGO2 cytosol annotation; the title is preserved exactly. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9011958 (miR-26A and B bind to the 3'UTR of the GREB1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9012203 (miR-26A and B bind to the 3'UTR of the CHD11 mRNA) supplies the original compartment assertion. The machine-fetched title names CHD11, while the cached summary names CHD1. Target identity is internally inconsistent and is not silently repaired. The source-level cytosol judgment has independent AGO2 localization support. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9012208 (miR-26A and B bind to the 3'UTR of the KPNA2 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9023909 (C3PO hydrolyzes cleaved passenger strand) supplies the original compartment assertion. The summary distinguishes AGO2 passenger-strand cleavage from subsequent C3PO-mediated fragment degradation; C3PO activity is not assigned to AGO2. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9023912 (AGO2 cleaves passenger strand of duplex siRNA) supplies the original compartment assertion. The summary describes guide loading and AGO2 passenger-strand cleavage, with C3PO acting subsequently. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9038545 (miR-613 binds to the 3'UTR of the NR1H3 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9618392 (miR-26 binds to the 3'UTR of the ARL4C mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9618486 (miR-26 binds to the 3'UTR of the ABCA1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9624925 (miR-33 binds to the 3'UTR of the ABCA1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9657791 (miR-144 binds to the 3'UTR of the ABCA1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9759950 (miR-200c-3p binds CDH11 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9768616 (miR-9 binds CDH1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9768643 (miR-10b binds CDH1 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9768788 (miR-224 binds NPAS4 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9860139 (MIR27B microRNA binds 3'UTR of TGFBR3 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9860160 (MIR-Let7-a1 microRNA binds 3'UTR of TGFBR3 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9860168 (MIR23B microRNA binds 3'UTR of TGFBR3 mRNA) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9924908 (CD274 mRNA binds miR-93 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9924921 (CD274 mRNA binds miR-34 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9924968 (CD274 mRNA binds miR-429 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925087 (CD274 mRNA binds miR-138-5p RISC) supplies the original compartment assertion. The title names miR-138-5p but portions of the summary name miR-429-5p. The internal target-guide discrepancy is recorded without changing the machine-fetched title or using it as proof of AGO2 slicing. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925095 (CD274 mRNA binds miR-340 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925158 (CD274 mRNA binds miR-152 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925159 (CD274 mRNA binds miR-140 RISC) supplies the original compartment assertion. The title names miR-140 but a summary sentence names miR-34a. The guide discrepancy limits detailed mechanistic use; the broad cytosol annotation is independently supported. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925246 (CD274 mRNA binds miR-Let7-a1 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925270 (CD274 mRNA binds miR-148a-3p RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925289 (CD274 mRNA binds miR-424 RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925320 (CD274 mRNA binds miR-142-5p RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: The Reactome source places AGO2 in the cytosol in this RNA-regulatory context.

Reason: Reactome:R-HSA-9925324 (CD274 mRNA binds miR-200B/C RISC) supplies the original compartment assertion. The cached event describes small-RNA-directed target regulation or guide handling. A decrease in target abundance is not treated as proof of AGO2 endonucleolysis, and the event summary is not a new direct localization assay. Cytosolic AGO2-containing silencing complexes are independently established in human cells, so the broad source compartment is retained (PMID:17932509).

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The available primary material concerns Tudor-SN cleavage of AGO2-associated miRNAs. Tudor-SN is the nuclease in that reaction; being associated with its substrates does not make AGO2 the executing enzyme. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes Roquin interaction with AGO2 and miR-146a regulation. Disease effects of Roquin mutants do not define an independent AGO2 catalytic mechanism. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports placental-cell invasion and endothelial angiogenic behavior in the reported models.

Reason: The primary abstract reports AGO2-linked trophoblast invasion and endothelial tube formation in HTR8/SVneo and HUVEC models. These source-level experimental process annotations are retained as context-specific regulatory outcomes, without inferring a separate motility or angiogenesis enzyme activity (PMID:27208409).

Summary: AGO2 supports placental-cell invasion and endothelial angiogenic behavior in the reported models.

Reason: The primary abstract reports AGO2-linked trophoblast invasion and endothelial tube formation in HTR8/SVneo and HUVEC models. These source-level experimental process annotations are retained as context-specific regulatory outcomes, without inferring a separate motility or angiogenesis enzyme activity (PMID:27208409).

Summary: AGO2 supports P-body in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full paper examines TRIM71 association with Argonaute and P-body localization while testing earlier AGO2 degradation models. Retaining localization does not endorse every proposed ubiquitination mechanism. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710).

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source examines RNA helicase A in human RISC assembly. AGO2 complex membership/loading is retained with curator deference and independent reconstituted RLC support; RNA helicase activity belongs to the partner, not AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source distinguishes RHA/DHX9 RNA-binding domains and RNA-dependent AGO2 association. It supports an RNP interaction, not an unqualified direct protein–protein affinity or AGO2 helicase activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 is detected within human pericardial-fluid exosome preparations.

Reason: The full source identifies AGO2 in the preparation and recovers associated miRNAs by AGO2 IP. Proteinase-K/RNase resistance before sonication and susceptibility after membrane disruption strengthen the encapsulation assignment. This establishes the reported extracellular pool, not universal AGO2 secretion or that transferred AGO2 protein causes every angiogenic effect (PMID:28159509, Figure 4 and Figure S3).

Summary: The PACT-associated complex is established, but this source-specific precursor-processing assignment remains unresolved.

Reason: The cached abstract of PMID:16424907 establishes a PACT-associated complex containing Dicer, AGO2 and TRBP and reports effects of PACT depletion on mature miRNA accumulation. It does not resolve which AGO2 action contributes to precursor conversion. PMC1383527 and publisher full-text retrieval remained inaccessible in this follow-up, so the original IDA judgment is deferred rather than declared wrong. Independent primary evidence establishes direct human AGO2 precursor cleavage: recombinant hAGO2 cleaved the short pre-miR-451 hairpin to a 30-nt intermediate in PMID:20448148 Figure 2B. Subsequent 3-prime trimming is a separate step. This substrate-specific reaction is distinct from Dicer cleavage of canonical pre-miRNAs and from guide loading. That independent activity does not identify the experiment supporting this particular PACT-paper annotation.

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710). PMID:23661684 explicitly reconstitutes both Dicer–TRBP–AGO2 and Dicer–PACT–AGO2 preparations.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract reports RNA-dependent nesprin-1 p50 association with AGO2/RCK and cytoplasmic processing-body organization. It does not establish an RNA-independent direct binary contact for all partners. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source describes GIGYF2 association with AGO2 and repression by tethered GIGYF2. Effector activity measured for a partner is not automatically intrinsic AGO2 activity. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source supports eIF4GI-dependent miRNA repression and AGO2 association with cap-bound complexes. Figure 7 cap-specific photocrosslinking of cellular complexes establishes direct contact or close proximity, in the authors' wording, and enhancement by eIF4GI. It does not resolve intrinsic selective cap binding by isolated AGO2 or prove direct eIF4GI–AGO2 contact. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 association with cap-containing complexes is established; intrinsic cap recognition remains disputed.

Reason: PMID:17524464 proposed intrinsic MID-domain cap recognition. PMID:19159466 challenges the motif structurally, and PMID:21475248 found no selective cap binding by the isolated MID domain or active recombinant AGO2 lacking its N-terminal proline-rich segment. In contrast, PMID:23409027 shows cap photocrosslinking/proximity in cellular AGO2 complexes enhanced by eIF4GI. These assay contexts do not resolve whether AGO2 itself selectively recognizes the cap or is positioned there by cofactors. Direct cap-binding activity remains UNDECIDED; translation repression is independently retained.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract describes miR-16, TTP and Argonaute involvement in AU-rich-element-mediated RNA turnover in Drosophila and human cells. TTP is reported to associate through Argonaute rather than binding miR-16 directly. It supports a regulatory RNP context, not a unique generic protein-binding function. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract reports human RISC association with MOV10 and 60S-ribosomal proteins, including eIF6, and effects of eIF6 depletion on miRNA repression. Ribosome anti-association is attributed to eIF6; complex membership does not make AGO2 a canonical translation initiation factor or MOV10 helicase. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 contributes to let-7i-associated IL2 promoter activation.

Reason: AGO2 depletion reduces promoter activation and AGO2 is recruited to the promoter in the full human-cell study. These results support positive transcriptional regulation by an RNA-guided nuclear complex; they do not resolve intrinsic AGO2 sequence-specific DNA recognition (PMID:25336585).

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796).

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710).

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710).

Summary: Promoter recruitment is established, while the precise sequence-specific DNA-binding role of AGO2 is unresolved.

Reason: The full source shows let-7i-dependent IL2 promoter activation, AGO1/AGO2 knockdown effects, promoter ChIP, and association with PolII/TBP in human-cell experiments. Promoter/guide sequence substitutions support an RNA-guided complex mechanism. ChIP and reporter assays do not uniquely distinguish AGO2 sequence-specific DNA contact from recruitment through RNA/protein components. The original IMP inference is preserved. Guide-dependent recruitment could support a promoter-bound complex without establishing which component recognizes DNA; neither a direct DNA contact nor its absence is asserted.

Summary: AGO2 supports nucleus in the specified molecular or cellular context.

Reason: AGO2 has an experimentally supported nuclear pool, including human-cell nuclear RNA targeting and promoter-associated regulation. This is retained as a contextual compartment alongside its major cytoplasmic silencing roles (PMID:19167051; PMID:23985560; PMID:25336585).

Summary: AGO2 associates with the RNA polymerase II transcription machinery in the IL2 promoter system.

Reason: The full human-cell source reports AGO2-containing complexes with PolII/TBP and promoter recruitment. The informative PolII-complex-binding term is retained as a contextual interaction; it does not imply that AGO2 supplies PolII catalytic activity or directly contacts promoter DNA (PMID:25336585).

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The full source shows let-7i-dependent IL2 promoter activation, AGO1/AGO2 knockdown effects, promoter ChIP, and association with PolII/TBP in human-cell experiments. Promoter/guide sequence substitutions support an RNA-guided complex mechanism. ChIP and reporter assays do not uniquely distinguish AGO2 sequence-specific DNA contact from recruitment through RNA/protein components. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports endoribonuclease activity, cleaving miRNA-paired mRNA in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports siRNA-mediated gene silencing by mRNA destabilization in the specified molecular or cellular context.

Reason: AGO2 executes guide-dependent target endonucleolysis. The formal GO term describes cleavage-mediated destabilization; AGO2 also recruits nonnucleolytic decay machinery, which is a separate mechanism and is not the sole basis for this annotation (PMID:15260970; PMID:18771919).

Summary: AGO2 supports miRNA processing in the specified molecular or cellular context.

Reason: AGO2 contributes to production of functional miRNA through guide loading and RISC maturation, and as part of experimentally reconstituted precursor-processing/loading complexes. Dicer performs canonical RNaseIII cleavage; AGO2 binding, guide selection and passenger removal are distinct contributions. This general maturation role is shared across human Argonautes and is not justified solely by an AGO2-specific precursor pathway (PMID:19966796; PMID:18178619; PMID:23661684). PMID:23661684 measures processing by AGO2-containing trimeric complexes; the Dicer partner performs precursor cleavage.

Summary: This source directly establishes AGO2 RISC assembly rather than cleavage of the tested precursor.

Reason: The full cached PMID:19966796 distinguishes duplex-loaded pre-RISC from guide-containing mature RISC. Its recombinant AGO2 is explicitly devoid of dicing activity on the tested pre-miR-luc; undiced hairpin can instead serve as a long guide in a bypass reaction. AGO2 directly contacts the duplex and supports passenger removal and maturation, making GO:0070922 RISC complex assembly the source-supported process. This does not deny the separate short-hairpin cleavage established for pre-miR-451 in PMID:20448148.

Proposed replacements: RISC complex assembly

Summary: AGO2 supports miRNA processing in the specified molecular or cellular context.

Reason: AGO2 contributes to production of functional miRNA through guide loading and RISC maturation, and as part of experimentally reconstituted precursor-processing/loading complexes. Dicer performs canonical RNaseIII cleavage; AGO2 binding, guide selection and passenger removal are distinct contributions. This general maturation role is shared across human Argonautes and is not justified solely by an AGO2-specific precursor pathway (PMID:19966796; PMID:18178619; PMID:23661684). In PMID:19966796 the contribution is functional guide maturation/loading, not an assertion that AGO2 performs Dicer cleavage.

Summary: AGO2 supports double-stranded RNA binding in the specified molecular or cellular context.

Reason: Human AGO2 accepts small-RNA duplexes during pre-RISC assembly before passenger-strand removal. Duplex binding is a supported loading state; it does not imply nonspecific recognition of all long dsRNA (PMID:19966796).

Summary: AGO2 supports single-stranded RNA binding in the specified molecular or cellular context.

Reason: AGO2 retains a single-stranded guide after duplex unwinding and also engages target RNA. This broad binding state is experimentally meaningful and is not replaced by miRNA specificity alone (PMID:19966796; PMID:15260970).

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796).

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710). The original PMID:19966796 Discussion distinguishes its pre-RISC intermediates from the previously designated Dicer/TRBP/AGO2 complex; that paper alone must not be used as proof of identical complex composition.

Summary: AGO2 supports RISC complex assembly in the specified molecular or cellular context.

Reason: AGO2 participates directly in RISC assembly by accepting a duplex, retaining a guide, and releasing or cleaving its passenger strand. It is an executing component of the assembly pathway, not merely a substrate whose abundance changes (PMID:19966796).

Summary: AGO2 supports endoribonuclease activity, cleaving miRNA-paired mRNA in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports siRNA-mediated gene silencing by mRNA destabilization in the specified molecular or cellular context.

Reason: AGO2 executes guide-dependent target endonucleolysis. The formal GO term describes cleavage-mediated destabilization; AGO2 also recruits nonnucleolytic decay machinery, which is a separate mechanism and is not the sole basis for this annotation (PMID:15260970; PMID:18771919).

Summary: AGO2 supports cytoplasm in the specified molecular or cellular context.

Reason: Cytoplasmic AGO2-containing RNA complexes execute post-transcriptional silencing. The broad compartment is valid at the source resolution, even though particular AGO2 pools also occupy granules or membranes (PMID:17932509; PMID:19801630).

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports miRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds miRNA guides in RISC. This is a defining molecular activity, distinct from binding the target mRNA. Human AGO complexes and loading experiments directly support the activity (PMID:15260970; PMID:19966796).

Summary: AGO2 supports miRNA-mediated gene silencing by mRNA destabilization in the specified molecular or cellular context.

Reason: AGO2 executes guide-dependent target endonucleolysis. The formal GO term describes cleavage-mediated destabilization; AGO2 also recruits nonnucleolytic decay machinery, which is a separate mechanism and is not the sole basis for this annotation (PMID:15260970; PMID:18771919).

Summary: AGO2 supports endoribonuclease activity, cleaving siRNA-paired mRNA in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: AGO2 supports RNA endonuclease activity in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619).

Summary: Reconstituted AGO2 selects and loads a guide while Dicer cleaves the canonical precursor.

Reason: The full author PDF of PMID:18178619 (Figures 2B, 3 and 4) assigns conversion of pre-let-7 to a duplex to Dicer, with the same product size from Dicer alone. AGO2 supplies guide loading, strand selection and target slicing, and dissociates after loading. GO:0070922 RISC complex assembly captures this directly demonstrated AGO2 work; membership in a dicing complex alone does not establish an AGO2 step in precursor conversion. Independent human AGO2 cleavage of the distinct pre-miR-451 substrate is supported by PMID:20448148.

Proposed replacements: RISC complex assembly

Summary: AGO2 supports RISC-loading complex in the specified molecular or cellular context.

Reason: The defined human Dicer–TRBP–AGO2 RISC-loading complex has been isolated and reconstituted. AGO2 receives and retains the guide. This physical trimer must be distinguished from duplex-bound pre-RISC intermediates, which need not have that exact composition (PMID:18178619; PMID:19820710).

Summary: AGO2 supports siRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds siRNA guides that specify RNA targets for RISC. The activity is directly established for human AGO2; partner enzymes that generate or phosphorylate the guide are not being assigned to AGO2 (PMID:15260970; PMID:15973356). PMID:19701182 Figure 5c supports AGO2 binding of a processed RMRP-derived sense small RNA; no AGO2 RNA-dependent polymerase activity is inferred.

Summary: AGO2 supports membrane in the specified molecular or cellular context.

Reason: Membrane association is supported independently by HEK293T membrane flotation with calnexin and HSP90 fraction controls (PMID:14749716, full Figure 6 read externally). The original YTS proteomics peptide assignment was not independently recovered, so its HDA compartment is retained with curator deference at the broad membrane-associated resolution. Neither integral membrane insertion nor contamination is inferred.

Summary: AGO2 supports RNA binding in the specified molecular or cellular context.

Reason: AGO2 directly binds small guide RNAs and their RNA targets. The broad source-level binding term is correct; a generic nucleic-acid label does not assert DNA binding, and an RNA-interactome assay need not resolve the guide/target distinction (PMID:15260970; PMID:19167051). PMID:22658674 is a HeLa-cell RNA-interactome capture source; supplementary peptide assignments were not independently reanalyzed.

Summary: AGO2 supports RNA binding in the specified molecular or cellular context.

Reason: AGO2 directly binds small guide RNAs and their RNA targets. The broad source-level binding term is correct; a generic nucleic-acid label does not assert DNA binding, and an RNA-interactome assay need not resolve the guide/target distinction (PMID:15260970; PMID:19167051). PMID:22681889 captures mRNA-associated proteins. The broad HDA term is retained at that experimental resolution.

Summary: AGO2 supports regulatory ncRNA-mediated gene silencing in the specified molecular or cellular context.

Reason: AGO2 carries out regulatory-RNA-directed silencing by binding a guide, recognizing its RNA target, and either cleaving sufficiently paired targets or recruiting silencing effectors. These are direct contributions rather than a downstream phenotype alone (PMID:15260970; PMID:19324964).

Summary: AGO2 supports positive regulation of nuclear-transcribed mRNA poly(A) tail shortening in the specified molecular or cellular context.

Reason: AGO2 promotes poly(A)-tail shortening and subsequent decay through TNRC6-dependent effector recruitment. Human AGO tethering and pulse-chase experiments in mouse NIH3T3 cells directly show this contribution. PAN2–PAN3 and CCR4–CAF1 catalyze the hydrolysis, while AGO2 targets and recruits the machinery; the regulatory process is therefore core (PMID:19838187).

Summary: AGO2 supports positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay in the specified molecular or cellular context.

Reason: AGO2 promotes poly(A)-tail shortening and subsequent decay through TNRC6-dependent effector recruitment. Human AGO tethering and pulse-chase experiments in mouse NIH3T3 cells directly show this contribution. PAN2–PAN3 and CCR4–CAF1 catalyze the hydrolysis, while AGO2 targets and recruits the machinery; the regulatory process is therefore core (PMID:19838187).

Summary: AGO2 supports P-body in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract reports APOBEC3G/3F association with AGO2-containing RNPs and P-body localization. RNA-containing co-complex association is not automatically a direct binary protein contact or a new enzymatic activity of AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source examines AGO2/APOBEC proteins in P-bodies and HIV-related experiments. P-body localization remains supported even where proposed antiviral effects are not established. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract describes affinity-purified human AGO1/AGO2 complexes containing MOV10, TNRC6B and precursor miRNAs. Complex association supports silencing machinery; it does not make AGO2 the helicase or prove every recovered pair is direct. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The source describes LIMD1/Ajuba/WTIP interactions linking AGO2-containing miRISC to cap-associated translation machinery and P-bodies. Adaptor function is experimentally attributed to the LIM proteins; this does not by itself demonstrate direct cap recognition by AGO2. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports cytoplasm in the specified molecular or cellular context.

Reason: Cytoplasmic AGO2-containing RNA complexes execute post-transcriptional silencing. The broad compartment is valid at the source resolution, even though particular AGO2 pools also occupy granules or membranes (PMID:17932509; PMID:19801630). PMID:20014101 reports ectopic AGO1/AGO2 colocalization in a mouse ZAR1-like study; independent cytoplasmic AGO2 evidence supports curator deference.

Summary: Generic protein binding does not describe a distinct AGO2 molecular function.

Reason: The abstract describes RBM4 and AGO2-associated miRNA repression in C2C12 myoblasts and cytoplasmic granules. This cellular context supports the core repression/initiation-inhibition mechanism; a mouse cell background alone does not establish that the human AGO2 annotation is misattributed. Remove the uninformative generic term under the binding-term policy, without asserting that the recorded interaction is absent. No partner enzymatic activity or unsupported adaptor function is substituted.

Summary: AGO2 supports miRNA-mediated gene silencing by inhibition of translation in the specified molecular or cellular context.

Reason: Guide-loaded AGO2 recruits miRISC effectors that inhibit target translation, including initiation-stage repression in the reported contexts. This belongs to its core silencing role. Uncertainty about intrinsic cap recognition does not negate repression, nor does AGO2 independently perform all downstream effector reactions (PMID:19324964; PMID:18771919). PMID:19801630 examines RBM4 recruitment of AGO2 during myoblast differentiation; the model-specific deployment does not make the underlying translation-repression mechanism non-core.

Summary: AGO2 supports negative regulation of translational initiation in the specified molecular or cellular context.

Reason: Guide-loaded AGO2 recruits miRISC effectors that inhibit target translation, including initiation-stage repression in the reported contexts. This belongs to its core silencing role. Uncertainty about intrinsic cap recognition does not negate repression, nor does AGO2 independently perform all downstream effector reactions (PMID:19324964; PMID:18771919). PMID:19801630 reports cap-dependent repression associated with RBM4/AGO2. Initiation inhibition is retained without asserting that AGO2 itself is a canonical initiation factor.

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports P-body in the specified molecular or cellular context.

Reason: AGO2 is a constituent of cytoplasmic RNA granules, including P-bodies. Independent localization and RNP studies support this compartment. Occupancy is distinct from a requirement for visible P-bodies in every silencing reaction or a demonstrated role in nucleating them (PMID:31400113; PMID:16756390).

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 supports endoribonuclease activity, cleaving siRNA-paired mRNA in the specified molecular or cellular context.

Reason: AGO2 is the RNA-guided catalytic subunit of human RISC and cleaves sufficiently complementary target RNA. Guide-dependent endonucleolysis is directly supported by human Argonaute comparisons and reconstituted AGO2-containing complexes; partner Dicer cleavage is a different reaction (PMID:15260970; PMID:18178619). PMID:17524464 distinguishes preserved catalytic activity from cap-motif mutant repression effects, so the cap-binding dispute does not invalidate slicing.

Summary: AGO2 association with cap-containing complexes is established; intrinsic cap recognition remains disputed.

Reason: PMID:17524464 proposed intrinsic MID-domain cap recognition. PMID:19159466 challenges the motif structurally, and PMID:21475248 found no selective cap binding by the isolated MID domain or active recombinant AGO2 lacking its N-terminal proline-rich segment. In contrast, PMID:23409027 shows cap photocrosslinking/proximity in cellular AGO2 complexes enhanced by eIF4GI. These assay contexts do not resolve whether AGO2 itself selectively recognizes the cap or is positioned there by cofactors. Direct cap-binding activity remains UNDECIDED; translation repression is independently retained.

Summary: AGO2 supports siRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds siRNA guides that specify RNA targets for RISC. The activity is directly established for human AGO2; partner enzymes that generate or phosphorylate the guide are not being assigned to AGO2 (PMID:15260970; PMID:15973356).

Summary: AGO2 supports RISC complex in the specified molecular or cellular context.

Reason: AGO2 is the guide-binding effector within RISC, with catalytic cleavage or effector recruitment depending on guide–target pairing. Human AGO complex isolation and functional guide loading directly establish membership; this does not imply that every RISC has an identical complement of accessory proteins (PMID:15260970; PMID:18178619).

Summary: AGO2 overexpression enhances pre-let-7 conversion in human cell extracts.

Reason: The externally read full PMID:17671087 Results and Figure 1 directly assay conversion of synthetic pre-let-7 to mature let-7 in HEK293F extracts. AGO2 overexpression increases the processing output, whereas additional Dicer/TRBP alone does not. This supports the original precursor-processing process at the assay level, with curator deference for IDA. The experiment does not isolate the AGO2 catalytic contribution or separate processing rate from product stabilization. Direct human AGO2 cleavage of another precursor, pre-miR-451, is independently demonstrated in PMID:20448148 and is not attributed to the let-7 assay.

Summary: AGO2 supports siRNA binding in the specified molecular or cellular context.

Reason: AGO2 binds siRNA guides that specify RNA targets for RISC. The activity is directly established for human AGO2; partner enzymes that generate or phosphorylate the guide are not being assigned to AGO2 (PMID:15260970; PMID:15973356). PMID:17495927 assigns siRNA phosphorylation to CLP1; AGO2 receives the guide and is not assigned the kinase reaction.

Summary: AGO2 supports miRNA-mediated gene silencing by inhibition of translation in the specified molecular or cellular context.

Reason: Guide-loaded AGO2 recruits miRISC effectors that inhibit target translation, including initiation-stage repression in the reported contexts. This belongs to its core silencing role. Uncertainty about intrinsic cap recognition does not negate repression, nor does AGO2 independently perform all downstream effector reactions (PMID:19324964; PMID:18771919).