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**
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GO:0035278
miRNA-mediated gene silencing by inhibition of translation
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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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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
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
All evidence summarized below pertains to Homo sapiens Argonaute-3 (AGO3; synonym EIF2C3), consistent with UniProt accession Q9H9G7 and membership in the eukaryotic Argonaute (Ago) subfamily that binds small RNAs in the miRNA/siRNA pathway. Primary studies explicitly purify and characterize human AGO3 protein and/or compare it directly to other human AGO paralogs (AGO1–AGO4), avoiding symbol ambiguity with non-human “AGO3” proteins. (park2017humanargonaute3has pages 1-1, park2020humanargonaute2and pages 1-2)
In mammals, Argonaute (AGO) proteins are the core effector proteins of the microRNA-induced silencing complex (miRISC), in which a loaded small RNA (typically a ~22-nt miRNA) guides the AGO-containing complex to complementary RNA targets to repress gene expression post-transcriptionally. RISC loading is coupled to DICER processing of small-RNA duplexes and involves chaperones HSC70/HSP90; canonical models emphasize ATP-dependent loading and passenger-strand removal to form a mature guide-loaded AGO. (narasimhan2025partnersinsilencing pages 1-2)
“Slicer” refers to RNA-guided endonuclease cleavage of a target RNA by an AGO protein’s PIWI domain (an RNase H-like fold). 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. However, human AGO3 retains the canonical catalytic tetrad and can cleave targets under specific conditions (guide-dependent), indicating that “non-slicer” is context-dependent for AGO3. (narasimhan2025partnersinsilencing pages 1-2, park2017humanargonaute3has pages 1-1)
Eukaryotic AGOs share a conserved architecture consisting of N, PAZ, MID, and PIWI domains connected by linker regions. In this framework, the PAZ domain anchors the guide RNA 3′ end and the MID domain binds the 5′ end, while the PIWI domain contains the catalytic center for cleavage when slicing occurs; structural features of the nucleic-acid binding channel shape guide/target geometry and substrate requirements. (martinmerchan2023domainorganizationexpression pages 5-6, park2017humanargonaute3has pages 7-8)
Reaction: When activated, AGO3 functions as an RNA-guided endoribonuclease, cleaving a complementary target RNA directed by a loaded guide RNA (miRNA/siRNA-like). (park2017humanargonaute3has pages 1-1)
Substrate specificity constraints: Experimental evidence indicates AGO3 slicing is highly dependent on the guide RNA identity and length and additionally requires extended target context (flanking regions) not required for AGO2. (park2017humanargonaute3has pages 1-1, park2017humanargonaute3has pages 7-8)
A foundational biochemical and structural study purified recombinant human AGO3 and showed:
Quantitative examples from figures: In the reported assays, AGO3 slicing with miR-20a showed measurable cleavage (e.g., ~7.0% in one guide condition), and concentration-dependent assays showed ~9.2–18.7% cleavage; the catalytic mutant eliminated cleavage. (park2017humanargonaute3has media c985c1a4)
The same study reported a 3.28 Å crystal structure of human AGO3-RISC (PDB referenced in text) showing:
These structural observations support a model in which AGO3 is catalytically competent but geometrically constrained, making cleavage difficult unless specific guide/target configurations are met. (park2017humanargonaute3has pages 1-1, park2017humanargonaute3has pages 7-8)
A subsequent study established that AGO3 can become a highly competent slicer when programmed with specific 14-nt guide RNAs, termed cleavage-inducing tiny guide RNAs (cityRNAs):
These results revise the operational definition of AGO3 as strictly “non-slicer,” showing length- and sequence-conditional activation.
A 2024 expert review integrates these findings into a mechanistic model in which 3′→5′ exonucleases trim AGO-associated miRNAs into ~13–14 nt tiny RNAs capable of activating AGO3:
Importantly, this review emphasizes a major open question: endogenous physiological target RNAs cleaved by AGO3 remain unknown. (nakanishi2024whenargonautetakes pages 1-3)
AGO3 participates in the canonical miRISC framework shared by mammalian AGOs, including assembly via the RISC loading complex and interactions with core miRISC cofactors (review-supported general mechanisms). (narasimhan2025partnersinsilencing pages 1-2, narasimhan2025partnersinsilencing pages 4-5)
Beyond cytoplasmic miRISC repression, AGO3 has been reported (via authoritative review synthesis of primary literature) to regulate pre-mRNA splicing in Th2 cells through a specific, RNA-independent nuclear interaction with SF3B3:
Direct AGO3 localization mapping is less extensive in the available sources than for AGO2, but two evidence-supported localization inferences are robust:
More generally, mammalian Argonaute proteins can accumulate in nuclei under particular conditions (e.g., environmental/cellular-state changes), highlighting compartmental plasticity of AGO biology; however, these data are AGO2-focused and should not be over-interpreted as AGO3-specific without direct AGO3 measurements. (chen2026decodingargonautespecificity pages 7-10)
The 2024 Journal of Biological Chemistry review frames AGO3 as a conditionally deployable slicer whose activation may be coupled to interferon-stimulated RNA metabolism (ISG20) and the generation of tiny RNAs/cityRNAs, potentially shifting slicing capacity toward AGO3 in antiviral states. It also highlights key unknowns, including the identity of endogenous AGO3 cleavage targets and when AGO3 slicing occurs in vivo. (nakanishi2024whenargonautetakes pages 9-11, nakanishi2024whenargonautetakes pages 1-3)
While not a direct functional assay, two 2023–2024 clinical lines of evidence incorporate AGO3 into real-world measurements:
Implementation status: AGO3 is being measured in human cohorts as an autoantigen/autoantibody target, but current evidence supports it more as part of broader Argonaute autoantibody panels than as a validated standalone biomarker.
Although not yet a clinical implementation, the discovery that 14-nt cityRNAs can strongly activate AGO3 slicing suggests potential future applications in:
However, the key limitation remains that physiological AGO3 cleavage targets have not been identified, and thus therapeutic exploitation is currently speculative and preclinical. (nakanishi2024whenargonautetakes pages 9-11, nakanishi2024whenargonautetakes pages 1-3)
Recent expert synthesis recognizes AGO3 as retaining the catalytic machinery (DEDH tetrad) and having the capacity for slicing under defined guide conditions, challenging earlier categorical statements that only AGO2 can slice. (nakanishi2024whenargonautetakes pages 1-3, narasimhan2025partnersinsilencing pages 4-5)
Structural data indicate AGO3’s active site is intact, but its nucleic-acid binding channel is less optimized than AGO2’s, providing a plausible mechanistic rationale for why AGO3 requires (i) specific guides (miR-20a/cityRNAs) and (ii) extended target flanks or specialized conformations to achieve cleavage. This supports a “regulated latent nuclease” model for AGO3. (park2017humanargonaute3has pages 1-1, park2017humanargonaute3has pages 7-8)
Authoritative reviews highlight outstanding gaps that limit complete functional annotation:
Human AGO3 (EIF2C3; Q9H9G7) is best annotated as a small-RNA-binding Argonaute effector with:
| Aspect | Key findings | Evidence type | Key sources (author year journal) with DOI URLs | Quantitative data/statistics (if any) |
|---|---|---|---|---|
| identity/domains | Target verified as human AGO3 / EIF2C3 / Argonaute-3, one of four human AGO paralogs. AGO3 has canonical Argonaute architecture (N, PAZ, MID, PIWI with linkers) and retains the catalytic DEDH tetrad in PIWI; crystal structure showed a complete active site but a less well-defined nucleic-acid binding channel than AGO2. (park2017humanargonaute3has pages 1-1, park2017humanargonaute3has pages 7-8, martinmerchan2023domainorganizationexpression pages 5-6) | structural, biochemical, review | Park et al. 2017 Nucleic Acids Res. https://doi.org/10.1093/nar/gkx916; Martín-Merchán et al. 2023 J Exp Bot. https://doi.org/10.1093/jxb/erad030 | Crystal structure resolved to 3.28 Å; catalytic residues visualized as D598, E638, D670, H808. (park2017humanargonaute3has pages 7-8, park2017humanargonaute3has media c985c1a4) |
| catalytic activity | AGO3 is not constitutively inactive: recombinant human AGO3 can cleave RNA when loaded with certain guides, establishing bona fide slicer activity under restricted conditions. This revises the older simplification that only AGO2 slices in humans. (park2017humanargonaute3has pages 1-1, park2020humanargonaute2and pages 1-2, narasimhan2025partnersinsilencing pages 4-5) | biochemical, structural, review | Park et al. 2017 Nucleic Acids Res. https://doi.org/10.1093/nar/gkx916; Park et al. 2020 PNAS https://doi.org/10.1073/pnas.2015026117; Narasimhan & Erkeland 2025 Non-Coding RNA https://doi.org/10.3390/ncrna11040062 | In Park 2017, AGO3 loaded with miR-20a showed measurable cleavage, including ~7.0% in one assay and 9.2–18.7% across concentration-dependent assays; catalytic mutant E638A abolished activity. (park2017humanargonaute3has media c985c1a4) |
| guide requirements | AGO3 cleavage is guide-sequence and guide-length dependent. miR-20a activates AGO3, whereas let-7a, miR-19b, and miR-16 do not in the reported assays. Later work showed specific 14-nt tyRNAs/cityRNAs (e.g., shortened miR-20a, let-7a, miR-27a, miR-17-92-family guides) strongly activate AGO3. (park2017humanargonaute3has pages 1-1, park2020humanargonaute2and pages 1-2, park2020humanargonaute2and pages 2-3) | biochemical | Park et al. 2017 Nucleic Acids Res. https://doi.org/10.1093/nar/gkx916; Park et al. 2020 PNAS https://doi.org/10.1073/pnas.2015026117 | 14-nt cityRNAs increased AGO3 cleavage up to ~82-fold; in lysate-based assays, FLAG-AGO3 reached ~50% cleavage with 14-nt miR-20a, whereas FLAG-AGO2 favored 23-nt duplex miR-20a at ~30% in the compared setup. (park2020humanargonaute2and pages 1-2) |
| target requirements | AGO3 has stricter substrate requirements than AGO2. Cleavage depends on the post-seed region of the guide and requires target RNAs with both 5′- and 3′-flanking regions around the complementary site; short minimal targets are poorly cleaved. (park2017humanargonaute3has pages 1-1, park2017humanargonaute3has pages 4-5, park2017humanargonaute3has pages 7-8) | biochemical, structural | Park et al. 2017 Nucleic Acids Res. https://doi.org/10.1093/nar/gkx916 | AGO3 cleaved a 60-nt miR-20a target but not a 23-nt target; deleting either 5′ or 3′ flanks drastically reduced activity. Seed substitutions at g7/g8 lowered cleavage. (park2017humanargonaute3has pages 7-8, park2017humanargonaute3has pages 4-5) |
| non-canonical roles | AGO3 also has an AGO3-specific nuclear role in pre-mRNA splicing in type 2 T cells, acting through an RNA-independent interaction with SF3B3 rather than through canonical cytoplasmic slicing alone. Reported consequences include control of global splicing and regulation of IL-13 via Nisch pre-mRNA. (narasimhan2025partnersinsilencing pages 10-11) | cellular, molecular, review | Narasimhan & Erkeland 2025 Non-Coding RNA https://doi.org/10.3390/ncrna11040062 | No direct effect size quoted in available context, but review describes AGO3 as essential for type 2 T-cell responses through this pathway. (narasimhan2025partnersinsilencing pages 10-11) |
| localization | Direct AGO3 localization evidence is limited in the available source set. AGO3 is clearly implicated in the nucleus for SF3B3-linked splicing in Th2 cells; broader human AGO literature supports nuclear AGO family presence, but AGO3-specific compartment maps remain less well resolved than for AGO2. (narasimhan2025partnersinsilencing pages 10-11, chen2026decodingargonautespecificity pages 7-10) | cellular, review | Narasimhan & Erkeland 2025 Non-Coding RNA https://doi.org/10.3390/ncrna11040062; Chen & Phillips 2026 RNA https://doi.org/10.1261/rna.080816.125 | Qualitative only in available context: nuclear AGO3 function inferred from the documented AGO3-SF3B3 splicing complex. (narasimhan2025partnersinsilencing pages 10-11) |
| interactions/complexes | In canonical RNA silencing, AGO3 participates in miRISC and likely shares core interactors such as GW182/TNRC6 and regulatory post-translational modification pathways with other mammalian AGOs. AGO3 additionally forms an RNA-independent nuclear complex with SF3B3 for splicing control. (narasimhan2025partnersinsilencing pages 10-11, narasimhan2025partnersinsilencing pages 1-2, narasimhan2025partnersinsilencing pages 4-5) | review, cellular | Narasimhan & Erkeland 2025 Non-Coding RNA https://doi.org/10.3390/ncrna11040062 | No AGO3-specific stoichiometric values in available context. Review notes AGO1/3/4 are generally considered non-slicer during passenger-strand removal, but AGO3 is an exception under specific guide conditions. (narasimhan2025partnersinsilencing pages 1-2, narasimhan2025partnersinsilencing pages 4-5) |
| disease/clinical associations | Available recent evidence links AGO3 to immune regulation and autoimmunity-related seroreactivity rather than a validated AGO3-specific therapy. AGO3 has been identified as an autoantigen target in systemic lupus erythematosus screens, and broader clinical literature/reviews suggest paralog-specific roles in disease, but AGO3-specific translational applications remain limited. (narasimhan2025partnersinsilencing pages 10-11) | clinical proteomic/screening context, review | Narasimhan & Erkeland 2025 Non-Coding RNA https://doi.org/10.3390/ncrna11040062 | No robust AGO3-only clinical performance metric available in the cited AGO3-specific context; evidence is currently more mechanistic than implementational. (narasimhan2025partnersinsilencing pages 10-11) |
Table: This table summarizes validated functional annotation evidence for human AGO3 (UniProt Q9H9G7/EIF2C3), separating AGO3-specific findings from broader Argonaute-family statements. It highlights where evidence is strong (conditional slicer activity, structural features, nuclear splicing role) and where AGO3-specific data remain limited (localization, clinical implementation).
References
(park2017humanargonaute3has pages 1-1): Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H. Hinckley, James A. Brackbill, Vicki H. Wysocki, and Kotaro Nakanishi. Human argonaute3 has slicer activity. Nucleic Acids Research, 45:11867-11877, Oct 2017. URL: https://doi.org/10.1093/nar/gkx916, doi:10.1093/nar/gkx916. This article has 148 citations and is from a highest quality peer-reviewed journal.
(park2020humanargonaute2and pages 1-2): Mi Seul Park, GeunYoung Sim, Audrey C. Kehling, and Kotaro Nakanishi. Human argonaute2 and argonaute3 are catalytically activated by different lengths of guide rna. Proceedings of the National Academy of Sciences, 117:28576-28578, Oct 2020. URL: https://doi.org/10.1073/pnas.2015026117, doi:10.1073/pnas.2015026117. This article has 67 citations and is from a highest quality peer-reviewed journal.
(narasimhan2025partnersinsilencing pages 1-2): Srinaath Narasimhan and Stefan J. Erkeland. Partners in silencing: decoding the mammalian argonaute interactome. Non-Coding RNA, 11:62, Aug 2025. URL: https://doi.org/10.3390/ncrna11040062, doi:10.3390/ncrna11040062. This article has 4 citations.
(martinmerchan2023domainorganizationexpression pages 5-6): Andrea Martín-Merchán, Belen Moro, Antoine Bouet, and Nicolas G Bologna. Domain organization, expression, subcellular localization, and biological roles of argonaute proteins in arabidopsis thaliana. Journal of experimental botany, 74:2374-2388, Feb 2023. URL: https://doi.org/10.1093/jxb/erad030, doi:10.1093/jxb/erad030. This article has 28 citations and is from a domain leading peer-reviewed journal.
(park2017humanargonaute3has pages 7-8): Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H. Hinckley, James A. Brackbill, Vicki H. Wysocki, and Kotaro Nakanishi. Human argonaute3 has slicer activity. Nucleic Acids Research, 45:11867-11877, Oct 2017. URL: https://doi.org/10.1093/nar/gkx916, doi:10.1093/nar/gkx916. This article has 148 citations and is from a highest quality peer-reviewed journal.
(park2017humanargonaute3has pages 1-2): Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H. Hinckley, James A. Brackbill, Vicki H. Wysocki, and Kotaro Nakanishi. Human argonaute3 has slicer activity. Nucleic Acids Research, 45:11867-11877, Oct 2017. URL: https://doi.org/10.1093/nar/gkx916, doi:10.1093/nar/gkx916. This article has 148 citations and is from a highest quality peer-reviewed journal.
(park2017humanargonaute3has media c985c1a4): Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H. Hinckley, James A. Brackbill, Vicki H. Wysocki, and Kotaro Nakanishi. Human argonaute3 has slicer activity. Nucleic Acids Research, 45:11867-11877, Oct 2017. URL: https://doi.org/10.1093/nar/gkx916, doi:10.1093/nar/gkx916. This article has 148 citations and is from a highest quality peer-reviewed journal.
(nakanishi2024whenargonautetakes pages 9-11): Kotaro Nakanishi. When argonaute takes out the ribonuclease sword. Journal of Biological Chemistry, 300:105499, Jan 2024. URL: https://doi.org/10.1016/j.jbc.2023.105499, doi:10.1016/j.jbc.2023.105499. This article has 25 citations and is from a domain leading peer-reviewed journal.
(nakanishi2024whenargonautetakes pages 1-3): Kotaro Nakanishi. When argonaute takes out the ribonuclease sword. Journal of Biological Chemistry, 300:105499, Jan 2024. URL: https://doi.org/10.1016/j.jbc.2023.105499, doi:10.1016/j.jbc.2023.105499. This article has 25 citations and is from a domain leading peer-reviewed journal.
(narasimhan2025partnersinsilencing pages 4-5): Srinaath Narasimhan and Stefan J. Erkeland. Partners in silencing: decoding the mammalian argonaute interactome. Non-Coding RNA, 11:62, Aug 2025. URL: https://doi.org/10.3390/ncrna11040062, doi:10.3390/ncrna11040062. This article has 4 citations.
(narasimhan2025partnersinsilencing pages 10-11): Srinaath Narasimhan and Stefan J. Erkeland. Partners in silencing: decoding the mammalian argonaute interactome. Non-Coding RNA, 11:62, Aug 2025. URL: https://doi.org/10.3390/ncrna11040062, doi:10.3390/ncrna11040062. This article has 4 citations.
(chen2026decodingargonautespecificity pages 7-10): Shihui Chen and C. Phillips. Decoding argonaute specificity: insights from c. elegans and beyond. RNA, 32:290-310, Dec 2026. URL: https://doi.org/10.1261/rna.080816.125, doi:10.1261/rna.080816.125. This article has 1 citations and is from a domain leading peer-reviewed journal.
(moadab2023argonautevaultand pages 1-3): Fatemeh Moadab, Xiaoxing Wang, Rayan Najjar, Kennedy C. Ukadike, Shaohui Hu, Tyler Hulett, Anders A. Bengtsson, Christian Lood, and Tomas Mustelin. Argonaute, vault, and ribosomal proteins targeted by autoantibodies in systemic lupus erythematosus. The Journal of Rheumatology, 50:1136-1144, May 2023. URL: https://doi.org/10.3899/jrheum.2022-1327, doi:10.3899/jrheum.2022-1327. This article has 9 citations.
(moadab2023argonautevaultand pages 3-4): Fatemeh Moadab, Xiaoxing Wang, Rayan Najjar, Kennedy C. Ukadike, Shaohui Hu, Tyler Hulett, Anders A. Bengtsson, Christian Lood, and Tomas Mustelin. Argonaute, vault, and ribosomal proteins targeted by autoantibodies in systemic lupus erythematosus. The Journal of Rheumatology, 50:1136-1144, May 2023. URL: https://doi.org/10.3899/jrheum.2022-1327, doi:10.3899/jrheum.2022-1327. This article has 9 citations.
(wang2024argonaute2autoantibodiesa pages 2-3): Yixuan Wang, Yue Hu, Jiaqi Li, Huailu Ma, Zongqi Shi, Chaojing Wen, Yu Long, Ziwei Li, Hang Sun, Yixuan Yang, and Xiaofeng Shi. Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in hbv-related acute-on-chronic liver failure patients with cirrhosis. Frontiers in Cellular and Infection Microbiology, Jul 2024. URL: https://doi.org/10.3389/fcimb.2024.1407064, doi:10.3389/fcimb.2024.1407064. This article has 3 citations.
(wang2024argonaute2autoantibodiesa pages 3-6): Yixuan Wang, Yue Hu, Jiaqi Li, Huailu Ma, Zongqi Shi, Chaojing Wen, Yu Long, Ziwei Li, Hang Sun, Yixuan Yang, and Xiaofeng Shi. Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in hbv-related acute-on-chronic liver failure patients with cirrhosis. Frontiers in Cellular and Infection Microbiology, Jul 2024. URL: https://doi.org/10.3389/fcimb.2024.1407064, doi:10.3389/fcimb.2024.1407064. This article has 3 citations.
(moadab2023argonautevaultand pages 9-15): Fatemeh Moadab, Xiaoxing Wang, Rayan Najjar, Kennedy C. Ukadike, Shaohui Hu, Tyler Hulett, Anders A. Bengtsson, Christian Lood, and Tomas Mustelin. Argonaute, vault, and ribosomal proteins targeted by autoantibodies in systemic lupus erythematosus. The Journal of Rheumatology, 50:1136-1144, May 2023. URL: https://doi.org/10.3899/jrheum.2022-1327, doi:10.3899/jrheum.2022-1327. This article has 9 citations.
(wang2024argonaute2autoantibodiesa pages 9-10): Yixuan Wang, Yue Hu, Jiaqi Li, Huailu Ma, Zongqi Shi, Chaojing Wen, Yu Long, Ziwei Li, Hang Sun, Yixuan Yang, and Xiaofeng Shi. Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in hbv-related acute-on-chronic liver failure patients with cirrhosis. Frontiers in Cellular and Infection Microbiology, Jul 2024. URL: https://doi.org/10.3389/fcimb.2024.1407064, doi:10.3389/fcimb.2024.1407064. This article has 3 citations.
(park2020humanargonaute2and pages 2-3): Mi Seul Park, GeunYoung Sim, Audrey C. Kehling, and Kotaro Nakanishi. Human argonaute2 and argonaute3 are catalytically activated by different lengths of guide rna. Proceedings of the National Academy of Sciences, 117:28576-28578, Oct 2020. URL: https://doi.org/10.1073/pnas.2015026117, doi:10.1073/pnas.2015026117. This article has 67 citations and is from a highest quality peer-reviewed journal.
(park2017humanargonaute3has pages 4-5): Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H. Hinckley, James A. Brackbill, Vicki H. Wysocki, and Kotaro Nakanishi. Human argonaute3 has slicer activity. Nucleic Acids Research, 45:11867-11877, Oct 2017. URL: https://doi.org/10.1093/nar/gkx916, doi:10.1093/nar/gkx916. This article has 148 citations and is from a highest quality peer-reviewed journal.
(wang2024argonaute2autoantibodiesa pages 1-2): Yixuan Wang, Yue Hu, Jiaqi Li, Huailu Ma, Zongqi Shi, Chaojing Wen, Yu Long, Ziwei Li, Hang Sun, Yixuan Yang, and Xiaofeng Shi. Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in hbv-related acute-on-chronic liver failure patients with cirrhosis. Frontiers in Cellular and Infection Microbiology, Jul 2024. URL: https://doi.org/10.3389/fcimb.2024.1407064, doi:10.3389/fcimb.2024.1407064. This article has 3 citations.
id: Q9H9G7
gene_symbol: AGO3
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: '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.'
alternative_products:
- name: '1'
id: Q9H9G7-1
- name: '2'
id: Q9H9G7-2
sequence_note: VSP_041084
existing_annotations:
- term:
id: GO:0005634
label: nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: nucleus is a plausible or reported location/context but is not the core functional site
annotation for AGO3.
action: KEEP_AS_NON_CORE
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: cytoplasm is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0004521
label: RNA endonuclease activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: RNA endonuclease activity is supported for AGO3 as a conditional, guide-dependent
slicer activity.
action: ACCEPT
reason: AGO3 is not the canonical slicer like AGO2, but biochemical studies support guide- and
target-context-dependent RNA cleavage.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035194
label: regulatory ncRNA-mediated post-transcriptional gene silencing
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: regulatory ncRNA-mediated post-transcriptional gene silencing is consistent with AGO3
as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0016442
label: RISC complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0036464
label: cytoplasmic ribonucleoprotein granule
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: cytoplasmic ribonucleoprotein granule is consistent with AGO3 as a small-RNA-loaded
Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0031054
label: pre-miRNA processing
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: pre-miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis.
action: MARK_AS_OVER_ANNOTATED
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035198
label: miRNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: miRNA binding is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003727
label: single-stranded RNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: single-stranded RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0000932
label: P-body
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: P-body is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003676
label: nucleic acid binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: nucleic acid binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003723
label: RNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003725
label: double-stranded RNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: double-stranded RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003727
label: single-stranded RNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: single-stranded RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0016442
label: RISC complex
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0031047
label: regulatory ncRNA-mediated gene silencing
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: regulatory ncRNA-mediated gene silencing is consistent with AGO3 as a small-RNA-loaded
Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0031054
label: pre-miRNA processing
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: pre-miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis.
action: MARK_AS_OVER_ANNOTATED
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035198
label: miRNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: miRNA binding is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035278
label: miRNA-mediated gene silencing by inhibition of translation
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: miRNA-mediated gene silencing by inhibition of translation is consistent with AGO3 as a
small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035279
label: miRNA-mediated gene silencing by mRNA destabilization
evidence_type: IEA
original_reference_id: GO_REF:0000108
review:
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.
action: KEEP_AS_NON_CORE
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: |
Importantly, this review emphasizes a major open question: **endogenous physiological target RNAs cleaved by AGO3 remain unknown**.
- term:
id: GO:0036464
label: cytoplasmic ribonucleoprotein granule
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: cytoplasmic ribonucleoprotein granule is consistent with AGO3 as a small-RNA-loaded
Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0070578
label: RISC-loading complex
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: RISC-loading complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC
effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0070922
label: RISC complex assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: RISC complex assembly is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC
effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0072091
label: regulation of stem cell proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: regulation of stem cell proliferation is downstream or context-specific for AGO3.
action: KEEP_AS_NON_CORE
reason: This process may be supported in a particular experiment or pathway model, but it is
peripheral to the core Argonaute/RISC molecular role.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19167051
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19324964
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19383768
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23064648
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:28330616
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:28683311
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0000794
label: condensed nuclear chromosome
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: condensed nuclear chromosome is a plausible or reported location/context but is not the
core functional site annotation for AGO3.
action: KEEP_AS_NON_CORE
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: positive regulation of gene expression reflects a reported nuclear or regulatory
context rather than the main conserved AGO3 function.
action: KEEP_AS_NON_CORE
reason: Argonaute paralogs have reported nuclear/regulatory interactions, but the dominant
conserved function remains small-RNA-guided post-transcriptional repression.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:1901224
label: positive regulation of non-canonical NF-kappaB signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: positive regulation of non-canonical NF-kappaB signal transduction reflects a reported
nuclear or regulatory context rather than the main conserved AGO3 function.
action: KEEP_AS_NON_CORE
reason: Argonaute paralogs have reported nuclear/regulatory interactions, but the dominant
conserved function remains small-RNA-guided post-transcriptional repression.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035196
label: miRNA processing
evidence_type: NAS
original_reference_id: PMID:28781232
review:
summary: miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis.
action: MARK_AS_OVER_ANNOTATED
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0036464
label: cytoplasmic ribonucleoprotein granule
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: cytoplasmic ribonucleoprotein granule is consistent with AGO3 as a small-RNA-loaded
Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0004521
label: RNA endonuclease activity
evidence_type: IMP
original_reference_id: PMID:29040713
review:
summary: RNA endonuclease activity is supported for AGO3 as a conditional, guide-dependent
slicer activity.
action: ACCEPT
reason: AGO3 is not the canonical slicer like AGO2, but biochemical studies support guide- and
target-context-dependent RNA cleavage.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0090624
label: endoribonuclease activity, cleaving miRNA-paired mRNA
evidence_type: IMP
original_reference_id: PMID:29040713
review:
summary: endoribonuclease activity, cleaving miRNA-paired mRNA is supported for AGO3 as a
conditional, guide-dependent slicer activity.
action: ACCEPT
reason: AGO3 is not the canonical slicer like AGO2, but biochemical studies support guide- and
target-context-dependent RNA cleavage.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035196
label: miRNA processing
evidence_type: IMP
original_reference_id: PMID:22795694
review:
summary: miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis.
action: MARK_AS_OVER_ANNOTATED
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0031054
label: pre-miRNA processing
evidence_type: IDA
original_reference_id: PMID:19966796
review:
summary: pre-miRNA processing overstates the direct role of AGO3 in canonical miRNA biogenesis.
action: MARK_AS_OVER_ANNOTATED
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003725
label: double-stranded RNA binding
evidence_type: IDA
original_reference_id: PMID:19966796
review:
summary: double-stranded RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003727
label: single-stranded RNA binding
evidence_type: IDA
original_reference_id: PMID:19966796
review:
summary: single-stranded RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0016442
label: RISC complex
evidence_type: IDA
original_reference_id: PMID:19966796
review:
summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0070578
label: RISC-loading complex
evidence_type: IDA
original_reference_id: PMID:19966796
review:
summary: RISC-loading complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC
effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0070922
label: RISC complex assembly
evidence_type: IDA
original_reference_id: PMID:19966796
review:
summary: RISC complex assembly is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC
effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0090625
label: siRNA-mediated gene silencing by mRNA destabilization
evidence_type: IDA
original_reference_id: PMID:15260970
negated: true
review:
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.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:15260970
supporting_text: Purification of the FLAG/HA-epitope-tagged Ago containing complexes from
different human cell lines revealed that endonuclease activity is exclusively associated
with Ago2.
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: 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.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:15260970
review:
summary: cytoplasm is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0016442
label: RISC complex
evidence_type: IDA
original_reference_id: PMID:15260970
review:
summary: RISC complex is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035198
label: miRNA binding
evidence_type: IDA
original_reference_id: PMID:15260970
review:
summary: miRNA binding is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035279
label: miRNA-mediated gene silencing by mRNA destabilization
evidence_type: IDA
original_reference_id: PMID:15260970
negated: true
review:
summary: This older NOT annotation should be removed because later AGO3-specific evidence supports
guide-dependent miRNA-paired target cleavage.
action: REMOVE
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.
supported_by:
- reference_id: PMID:15260970
supporting_text: 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.
- reference_id: PMID:29040713
supporting_text: 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.
- term:
id: GO:0016020
label: membrane
evidence_type: HDA
original_reference_id: PMID:19946888
review:
summary: membrane is a plausible or reported location/context but is not the core functional
site annotation for AGO3.
action: KEEP_AS_NON_CORE
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.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003723
label: RNA binding
evidence_type: HDA
original_reference_id: PMID:22658674
review:
summary: RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0003723
label: RNA binding
evidence_type: HDA
original_reference_id: PMID:22681889
review:
summary: RNA binding is too generic for AGO3.
action: MARK_AS_OVER_ANNOTATED
reason: The informative molecular function is Argonaute small-RNA/miRNA binding within RISC
rather than a broad nucleic-acid or RNA-binding label.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1606561
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1606682
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912362
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912363
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912364
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912366
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912367
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912368
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1912406
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2318752
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-3209151
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-426489
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-426522
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-4518575
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5687103
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8935766
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8937097
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8937134
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8938440
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8938487
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8938507
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8944650
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8944684
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8944706
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9011958
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9012203
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9012208
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9038545
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9618392
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9618486
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9624925
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9657791
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9858289
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9858309
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9924921
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9925095
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9925158
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9925159
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9925324
review:
summary: cytosol is consistent with AGO3 as a small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0072091
label: regulation of stem cell proliferation
evidence_type: IMP
original_reference_id: PMID:23064648
review:
summary: regulation of stem cell proliferation is downstream or context-specific for AGO3.
action: KEEP_AS_NON_CORE
reason: This process may be supported in a particular experiment or pathway model, but it is
peripheral to the core Argonaute/RISC molecular role.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22915799
review:
summary: Generic protein binding does not capture the specific Argonaute/RISC function.
action: MARK_AS_OVER_ANNOTATED
reason: The cited interactions are best interpreted as RISC/cofactor context for
small-RNA-guided silencing, not as a standalone core function.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0006402
label: mRNA catabolic process
evidence_type: IDA
original_reference_id: PMID:18771919
review:
summary: mRNA catabolic process is downstream or context-specific for AGO3.
action: KEEP_AS_NON_CORE
reason: This process may be supported in a particular experiment or pathway model, but it is
peripheral to the core Argonaute/RISC molecular role.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- term:
id: GO:0035278
label: miRNA-mediated gene silencing by inhibition of translation
evidence_type: IDA
original_reference_id: PMID:18771919
review:
summary: miRNA-mediated gene silencing by inhibition of translation is consistent with AGO3 as a
small-RNA-loaded Argonaute/RISC effector.
action: ACCEPT
reason: The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression
and related RISC complexes or cytoplasmic RNP compartments.
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
Ensembl Compara
findings: []
- id: GO_REF:0000108
title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:15260970
title: Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.
findings: []
- id: PMID:18771919
title: Importance of translation and nonnucleolytic ago proteins for on-target RNA interference.
findings: []
- id: PMID:19167051
title: Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs.
findings: []
- id: PMID:19324964
title: The C-terminal half of human Ago2 binds to multiple GW-rich regions of GW182 and requires
GW182 to mediate silencing.
findings: []
- id: PMID:19383768
title: The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts
independently of Argonaute proteins.
findings: []
- id: PMID:19946888
title: Defining the membrane proteome of NK cells.
findings: []
- id: PMID:19966796
title: ATP-dependent human RISC assembly pathways.
findings: []
- id: PMID:22658674
title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
findings: []
- id: PMID:22681889
title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
findings: []
- id: PMID:22795694
title: Slicing-independent RISC activation requires the argonaute PAZ domain.
findings: []
- id: PMID:22915799
title: HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.
findings: []
- id: PMID:23064648
title: DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human
stem cell proliferation.
findings: []
- id: PMID:28330616
title: Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics.
findings: []
- id: PMID:28683311
title: Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent
Recruitment of LIM-Domain-Containing Proteins.
findings: []
- id: PMID:28781232
title: Multivalent Recruitment of Human Argonaute by GW182.
findings: []
- id: PMID:29040713
title: Human Argonaute3 has slicer activity.
findings: []
- id: Reactome:R-HSA-1606561
title: MIR449 microRNAs bind 3'UTR of NOTCH1 mRNA
findings: []
- id: Reactome:R-HSA-1606682
title: MIR34 microRNAs bind 3'UTR of NOTCH1 mRNA
findings: []
- id: Reactome:R-HSA-1912362
title: MIR150 microRNA binds 3'UTR of NOTCH3 mRNA
findings: []
- id: Reactome:R-HSA-1912363
title: MIR200B/C microRNAs bind NOTCH1 mRNA
findings: []
- id: Reactome:R-HSA-1912364
title: MIR181C microRNA binds 3'UTR of NOTCH4 mRNA
findings: []
- id: Reactome:R-HSA-1912366
title: MIR206 microRNA binds 3'UTR of NOTCH3 mRNA
findings: []
- id: Reactome:R-HSA-1912367
title: MIR34 microRNAs bind 3'UTR of NOTCH2 mRNA
findings: []
- id: Reactome:R-HSA-1912368
title: MIR302A microRNA binds 3'UTR of NOTCH4 mRNA
findings: []
- id: Reactome:R-HSA-1912406
title: p53 positively regulates transcription of MIR34 microRNAs
findings: []
- id: Reactome:R-HSA-2318752
title: miR-26A microRNAs bind PTEN mRNA
findings: []
- id: Reactome:R-HSA-3209151
title: miR-24 binds p16INK4A and p14ARF mRNAs
findings: []
- id: Reactome:R-HSA-426489
title: RISC binds inexactly matching target RNAs
findings: []
- id: Reactome:R-HSA-426522
title: Nonendonucleolytic RISC binds exactly matching target RNAs
findings: []
- id: Reactome:R-HSA-4518575
title: miR-92b binds 3'UTR of NLK mRNA
findings: []
- id: Reactome:R-HSA-5687103
title: FOXO3 regulates MIR34B,C expression
findings: []
- id: Reactome:R-HSA-8935766
title: miR-378 binds RUNX1 mRNA
findings: []
- id: Reactome:R-HSA-8937097
title: MIR27A gene transcription is stimulated by the complex containing RUNX1, PRMT1 and GATA1
and inhibited by the complex of RUNX1, SIN3A and PRMT6
findings: []
- id: Reactome:R-HSA-8937134
title: miR-27a binds RUNX1 mRNA
findings: []
- id: Reactome:R-HSA-8938440
title: miR-17 binds RUNX1 mRNA
findings: []
- id: Reactome:R-HSA-8938487
title: miR-20a binds RUNX1 mRNA
findings: []
- id: Reactome:R-HSA-8938507
title: miR-106a binds RUNX1 mRNA
findings: []
- id: Reactome:R-HSA-8944650
title: miR-214 microRNA binds PTEN mRNA
findings: []
- id: Reactome:R-HSA-8944684
title: miR-205 microRNA binds PTEN mRNA
findings: []
- id: Reactome:R-HSA-8944706
title: miR-21 nonendonucleolytic RISC binds PTEN mRNA
findings: []
- id: Reactome:R-HSA-9011958
title: miR-26A and B bind to the 3'UTR of the GREB1 mRNA
findings: []
- id: Reactome:R-HSA-9012203
title: miR-26A and B bind to the 3'UTR of the CHD11 mRNA
findings: []
- id: Reactome:R-HSA-9012208
title: miR-26A and B bind to the 3'UTR of the KPNA2 mRNA
findings: []
- id: Reactome:R-HSA-9038545
title: miR-613 binds to the 3'UTR of the NR1H3 mRNA
findings: []
- id: Reactome:R-HSA-9618392
title: miR-26 binds to the 3'UTR of the ARL4C mRNA
findings: []
- id: Reactome:R-HSA-9618486
title: miR-26 binds to the 3'UTR of the ABCA1 mRNA
findings: []
- id: Reactome:R-HSA-9624925
title: miR-33 binds to the 3'UTR of the ABCA1 mRNA
findings: []
- id: Reactome:R-HSA-9657791
title: miR-144 binds to the 3'UTR of the ABCA1 mRNA
findings: []
- id: Reactome:R-HSA-9858289
title: MITF-M-dependent miR-211 expression
findings: []
- id: Reactome:R-HSA-9858309
title: miR-211 RISC binds POU3F2 mRNA
findings: []
- id: Reactome:R-HSA-9924921
title: CD274 mRNA binds miR-34 RISC
findings: []
- id: Reactome:R-HSA-9925095
title: CD274 mRNA binds miR-340 RISC
findings: []
- id: Reactome:R-HSA-9925158
title: CD274 mRNA binds miR-152 RISC
findings: []
- id: Reactome:R-HSA-9925159
title: CD274 mRNA binds miR-140 RISC
findings: []
- id: Reactome:R-HSA-9925324
title: CD274 mRNA binds miR-200B/C RISC
findings: []
- id: file:human/AGO3/AGO3-uniprot.txt
title: UniProt text export for AGO3
findings:
- statement: UniProt identifies AGO3 and its protein family/domain context.
supporting_text: Belongs to the argonaute family. Ago subfamily.
- id: file:human/AGO3/AGO3-deep-research-falcon.md
title: Falcon deep research report for AGO3
findings:
- statement: Falcon research supports the reviewed core function of AGO3.
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
core_functions:
- description: Small-RNA-guided Argonaute/RISC effector function in post-transcriptional gene
silencing.
molecular_function:
id: GO:0035198
label: miRNA binding
directly_involved_in:
- id: GO:0035194
label: regulatory ncRNA-mediated post-transcriptional gene silencing
- id: GO:0035278
label: miRNA-mediated gene silencing by inhibition of translation
in_complex:
id: GO:0016442
label: RISC complex
locations:
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: Human **AGO3 (EIF2C3; Q9H9G7)** is best annotated as a **small-RNA-binding
Argonaute effector**
- description: Conditional RNA-guided endonuclease activity that depends on guide length/sequence
and target context.
molecular_function:
id: GO:0090624
label: endoribonuclease activity, cleaving miRNA-paired mRNA
in_complex:
id: GO:0016442
label: RISC complex
locations:
- id: GO:0005829
label: cytosol
supported_by:
- reference_id: file:human/AGO3/AGO3-deep-research-falcon.md
supporting_text: AGO3 cleavage is **guide-sequence and guide-length dependent**. miR-20a
activates AGO3, whereas let-7a, miR-19b, and miR-16 do not in the reported assays.
proposed_new_terms: []
suggested_questions:
- question: Which endogenous human tissues or stress states require AGO3-specific RISC activity
rather than redundant activity from other AGO paralogs?
- question: Which protein cofactors determine guide loading, localization, and non-core nuclear or
granule-associated functions of AGO3?
suggested_experiments:
- description: Endogenous tagging of AGO3 followed by small-RNA CLIP, target RNA profiling, and
paralog-specific rescue in AGO-depleted human cells.
experiment_type: genome editing/RNA-protein interaction profiling
hypothesis: AGO3 has paralog-specific guide, target, and compartment preferences within human RISC
biology.
- description: Biochemical reconstitution of AGO3-RISC with representative miRNA and siRNA guides to
compare target repression, target cleavage, and TNRC6 recruitment.
experiment_type: biochemical reconstitution
hypothesis: AGO3 activity is best explained by guide-loaded RISC function rather than generic RNA
or protein binding.