AGO3 encodes human Argonaute-3, a small-RNA-binding RISC effector with a context-restricted slicer activity. Its core function is Argonaute-mediated small-RNA-guided gene silencing, with biochemical evidence for guide- and target-context-dependent RNA endonuclease activity and a non-core nuclear splicing role reported in immune cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: nucleus is a plausible or reported location/context but is not the core functional site annotation for AGO3. Reason: The core location is cytoplasmic RISC/RNP granules; nuclear, membrane, synaptic, exosomal, or other compartment annotations should remain non-core unless tied to a specific curated mechanism. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0004521 RNA endonuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: RNA endonuclease activity is supported for AGO3 as a conditional, guide-dependent slicer activity. Reason: AGO3 is not the canonical slicer like AGO2, but biochemical studies support guide- and target-context-dependent RNA cleavage. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035194 regulatory ncRNA-mediated post-transcriptional gene silencing | IBA GO_REF:0000033 | ACCEPT | Summary: regulatory ncRNA-mediated post-transcriptional gene silencing is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0016442 RISC complex | IBA GO_REF:0000033 | ACCEPT | Summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasmic ribonucleoprotein granule is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0031054 pre-miRNA processing | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: pre-miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis. Reason: The better-supported role is as a loaded Argonaute effector after small-RNA processing, not as the Drosha/Dicer processing enzyme for pre-miRNAs. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035198 miRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: miRNA binding is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003727 single-stranded RNA binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: single-stranded RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0000932 P-body | IEA GO_REF:0000044 | ACCEPT | Summary: P-body is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: nucleic acid binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003723 RNA binding | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003725 double-stranded RNA binding | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: double-stranded RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003727 single-stranded RNA binding | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: single-stranded RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0016442 RISC complex | IEA GO_REF:0000120 | ACCEPT | Summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0031047 regulatory ncRNA-mediated gene silencing | IEA GO_REF:0000002 | ACCEPT | Summary: regulatory ncRNA-mediated gene silencing is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0031054 pre-miRNA processing | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: pre-miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis. Reason: The better-supported role is as a loaded Argonaute effector after small-RNA processing, not as the Drosha/Dicer processing enzyme for pre-miRNAs. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035198 miRNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: miRNA binding is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035278 miRNA-mediated gene silencing by inhibition of translation | IEA GO_REF:0000120 | ACCEPT | Summary: miRNA-mediated gene silencing by inhibition of translation is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035279 miRNA-mediated gene silencing by mRNA destabilization | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: miRNA-mediated gene silencing by mRNA destabilization is plausible for AGO3 only as a context-dependent non-core process, not as an unqualified core AGO3 function. Reason: AGO3 is primarily a small-RNA-binding RISC effector, and later biochemical work supports guide- and target-dependent slicing. Endogenous AGO3 cleavage targets remain unclear, so this broad IEA process should not be treated as a core positive annotation. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Importantly, this review emphasizes a major open question: **endogenous physiological target RNAs cleaved by AGO3 remain unknown**. |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IEA GO_REF:0000117 | ACCEPT | Summary: cytoplasmic ribonucleoprotein granule is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0070578 RISC-loading complex | IEA GO_REF:0000117 | ACCEPT | Summary: RISC-loading complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0070922 RISC complex assembly | IEA GO_REF:0000117 | ACCEPT | Summary: RISC complex assembly is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0072091 regulation of stem cell proliferation | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: regulation of stem cell proliferation is downstream or context-specific for AGO3. Reason: This process may be supported in a particular experiment or pathway model, but it is peripheral to the core Argonaute/RISC molecular role. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:19167051 Importin 8 is a gene silencing factor that targets argonaute... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:19324964 The C-terminal half of human Ago2 binds to multiple GW-rich ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:19383768 The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C s... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:23064648 DICER- and AGO3-dependent generation of retinoic acid-induce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:28330616 Systematic Analysis of Human Protein Phosphatase Interaction... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:28683311 Argonaute Utilization for miRNA Silencing Is Determined by P... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0000794 condensed nuclear chromosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: condensed nuclear chromosome is a plausible or reported location/context but is not the core functional site annotation for AGO3. Reason: The core location is cytoplasmic RISC/RNP granules; nuclear, membrane, synaptic, exosomal, or other compartment annotations should remain non-core unless tied to a specific curated mechanism. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of gene expression reflects a reported nuclear or regulatory context rather than the main conserved AGO3 function. Reason: Argonaute paralogs have reported nuclear/regulatory interactions, but the dominant conserved function remains small-RNA-guided post-transcriptional repression. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of non-canonical NF-kappaB signal transduction reflects a reported nuclear or regulatory context rather than the main conserved AGO3 function. Reason: Argonaute paralogs have reported nuclear/regulatory interactions, but the dominant conserved function remains small-RNA-guided post-transcriptional repression. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035196 miRNA processing | NAS PMID:28781232 Multivalent Recruitment of Human Argonaute by GW182. | MARK AS OVER ANNOTATED | Summary: miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis. Reason: The better-supported role is as a loaded Argonaute effector after small-RNA processing, not as the Drosha/Dicer processing enzyme for pre-miRNAs. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IDA GO_REF:0000052 | ACCEPT | Summary: cytoplasmic ribonucleoprotein granule is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0004521 RNA endonuclease activity | IMP PMID:29040713 Human Argonaute3 has slicer activity. | ACCEPT | Summary: RNA endonuclease activity is supported for AGO3 as a conditional, guide-dependent slicer activity. Reason: AGO3 is not the canonical slicer like AGO2, but biochemical studies support guide- and target-context-dependent RNA cleavage. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0090624 endoribonuclease activity, cleaving miRNA-paired mRNA | IMP PMID:29040713 Human Argonaute3 has slicer activity. | ACCEPT | Summary: endoribonuclease activity, cleaving miRNA-paired mRNA is supported for AGO3 as a conditional, guide-dependent slicer activity. Reason: AGO3 is not the canonical slicer like AGO2, but biochemical studies support guide- and target-context-dependent RNA cleavage. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035196 miRNA processing | IMP PMID:22795694 Slicing-independent RISC activation requires the argonaute P... | MARK AS OVER ANNOTATED | Summary: miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis. Reason: The better-supported role is as a loaded Argonaute effector after small-RNA processing, not as the Drosha/Dicer processing enzyme for pre-miRNAs. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0031054 pre-miRNA processing | IDA PMID:19966796 ATP-dependent human RISC assembly pathways. | MARK AS OVER ANNOTATED | Summary: pre-miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis. Reason: The better-supported role is as a loaded Argonaute effector after small-RNA processing, not as the Drosha/Dicer processing enzyme for pre-miRNAs. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003725 double-stranded RNA binding | IDA PMID:19966796 ATP-dependent human RISC assembly pathways. | MARK AS OVER ANNOTATED | Summary: double-stranded RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003727 single-stranded RNA binding | IDA PMID:19966796 ATP-dependent human RISC assembly pathways. | MARK AS OVER ANNOTATED | Summary: single-stranded RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0016442 RISC complex | IDA PMID:19966796 ATP-dependent human RISC assembly pathways. | ACCEPT | Summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0070578 RISC-loading complex | IDA PMID:19966796 ATP-dependent human RISC assembly pathways. | ACCEPT | Summary: RISC-loading complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0070922 RISC complex assembly | IDA PMID:19966796 ATP-dependent human RISC assembly pathways. | ACCEPT | Summary: RISC complex assembly is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0090625 siRNA-mediated gene silencing by mRNA destabilization | IDA NOT PMID:15260970 Human Argonaute2 mediates RNA cleavage targeted by miRNAs an... | ACCEPT | Summary: This NOT annotation is appropriate for the PMID:15260970 assay context; AGO3 did not behave as the AGO2-like siRNA-guided target-cleavage Argonaute in that study. Reason: PMID:15260970 supports AGO3 association with miRNAs/RISC but reports target-cleavage activity only for AGO2 in the tested assays. Later work supports conditional AGO3 slicing, so this NOT call should be treated as scoped to the 2004 AGO2-specific siRNA-cleavage context. Supporting Evidence: PMID:15260970 Purification of the FLAG/HA-epitope-tagged Ago containing complexes from different human cell lines revealed that endonuclease activity is exclusively associated with Ago2. file:human/AGO3/AGO3-deep-research-falcon.md Historically, mammalian **AGO2** was regarded as the only catalytically competent slicer, while AGO1/AGO3/AGO4 were categorized as non-slicer AGOs for most miRNA-mediated repression. |
| GO:0005737 cytoplasm | IDA PMID:15260970 Human Argonaute2 mediates RNA cleavage targeted by miRNAs an... | ACCEPT | Summary: cytoplasm is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0016442 RISC complex | IDA PMID:15260970 Human Argonaute2 mediates RNA cleavage targeted by miRNAs an... | ACCEPT | Summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035198 miRNA binding | IDA PMID:15260970 Human Argonaute2 mediates RNA cleavage targeted by miRNAs an... | ACCEPT | Summary: miRNA binding is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035279 miRNA-mediated gene silencing by mRNA destabilization | IDA NOT PMID:15260970 Human Argonaute2 mediates RNA cleavage targeted by miRNAs an... | REMOVE | Summary: This older NOT annotation should be removed because later AGO3-specific evidence supports guide-dependent miRNA-paired target cleavage. Reason: PMID:15260970 did not detect AGO3-dependent target cleavage in the tested 2004 assay, but PMID:29040713 supersedes that broad negative by demonstrating guide- and target-dependent AGO3 slicer activity. Supporting Evidence: PMID:15260970 The specific role of Ago2 in guiding target RNA cleavage was confirmed independently by siRNA-based depletion of individual Ago members in combination with a sensitive positive-readout reporter assay. PMID:29040713 recombinant AGO3 loaded with miR-20a cleaves complementary target RNAs, whereas AGO3 loaded with let-7a, miR-19b or miR-16 does not, indicating that AGO3 has slicer activity but that this activity depends on the guide RNA. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: membrane is a plausible or reported location/context but is not the core functional site annotation for AGO3. Reason: The core location is cytoplasmic RISC/RNP granules; nuclear, membrane, synaptic, exosomal, or other compartment annotations should remain non-core unless tied to a specific curated mechanism. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: RNA binding is too generic for AGO3. Reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1606561 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1606682 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912362 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912363 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912364 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912366 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912367 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912368 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1912406 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2318752 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3209151 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-426489 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-426522 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4518575 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5687103 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8935766 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8937097 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8937134 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8938440 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8938487 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8938507 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8944650 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8944684 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8944706 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9011958 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9012203 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9012208 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9038545 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9618392 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9618486 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9624925 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9657791 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9858289 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9858309 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9924921 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9925095 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9925158 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9925159 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9925324 | ACCEPT | Summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0072091 regulation of stem cell proliferation | IMP PMID:23064648 DICER- and AGO3-dependent generation of retinoic acid-induce... | KEEP AS NON CORE | Summary: regulation of stem cell proliferation is downstream or context-specific for AGO3. Reason: This process may be supported in a particular experiment or pathway model, but it is peripheral to the core Argonaute/RISC molecular role. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0005515 protein binding | IPI PMID:22915799 HIV-1 replication and APOBEC3 antiviral activity are not reg... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not capture the specific Argonaute/RISC function. Reason: The cited interactions are best interpreted as RISC/cofactor context for small-RNA-guided silencing, not as a standalone core function. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0006402 mRNA catabolic process | IDA PMID:18771919 Importance of translation and nonnucleolytic ago proteins fo... | KEEP AS NON CORE | Summary: mRNA catabolic process is downstream or context-specific for AGO3. Reason: This process may be supported in a particular experiment or pathway model, but it is peripheral to the core Argonaute/RISC molecular role. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
| GO:0035278 miRNA-mediated gene silencing by inhibition of translation | IDA PMID:18771919 Importance of translation and nonnucleolytic ago proteins fo... | ACCEPT | Summary: miRNA-mediated gene silencing by inhibition of translation is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector. Reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments. Supporting Evidence: file:human/AGO3/AGO3-deep-research-falcon.md Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding Argonaute effector** |
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Download this section (compressed HTML)Q: Which endogenous human tissues or stress states require AGO3-specific RISC activity rather than redundant activity from other AGO paralogs?
Q: Which protein cofactors determine guide loading, localization, and non-core nuclear or granule-associated functions of AGO3?
Experiment: Endogenous tagging of AGO3 followed by small-RNA CLIP, target RNA profiling, and paralog-specific rescue in AGO-depleted human cells.
Hypothesis: AGO3 has paralog-specific guide, target, and compartment preferences within human RISC biology.
Type: genome editing/RNA-protein interaction profiling
Experiment: Biochemical reconstitution of AGO3-RISC with representative miRNA and siRNA guides to compare target repression, target cleavage, and TNRC6 recruitment.
Hypothesis: AGO3 activity is best explained by guide-loaded RISC function rather than generic RNA or protein binding.
Type: biochemical reconstitution
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