AGO2 encodes Argonaute-2, the catalytic component of the microRNA-induced silencing complex (miRISC). Unlike other Argonaute proteins, AGO2 possesses endonuclease (slicing) activity that can directly cleave perfectly complementary mRNA targets. AGO2 is essential for miRNA-mediated gene silencing and has been implicated in various neurological disorders including Alzheimer's disease, Parkinson's disease, and ALS. This page covers AGO2 structure, function, disease associations, and therapeutic potential. [1]
| Property | Value | [2]
|----------|-------| [3]
| Gene Symbol | AGO2 | [4]
| Full Name | Argonaute-2 (EIF2C2) |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 27185 |
| OMIM ID | 606228 |
| Ensembl ID | ENSG00000139318 |
| UniProt ID | Q9UKV8 |
| Encoded Protein | Argonaute-2 |
| Protein Size | 859 amino acids (~97 kDa) |
| Associated Diseases | Alzheimer's disease, Parkinson's disease, ALS, cancer |
AGO2 contains the same domain structure as other Ago proteins:
The critical difference is that AGO2 has an intact catalytic DEDH tetrad (Asp-Asp-Glu-His) in its PIWI domain, enabling it to cleave (slice) perfectly matched targets.
AGO2 is the only catalytically active human Argonaute:
AGO2 is central to miRNA function:
In neurons:
AGO2 is essential for:
AGO2 in AD:
In PD:
In ALS:
AGO2 is frequently upregulated in cancers:
| Region | Expression Level |
|---|---|
| Cerebral cortex | Very high |
| Hippocampus | Very high |
| Cerebellum | High |
| Basal ganglia | High |
| Spinal cord | Moderate-High |
| Neurons | High |
| Astrocytes | Moderate |
| Development | Essential |
AGO2 is a therapeutic target:
Coyle et al. Metallothionein in neurodegeneration (1995). 1995. ↩︎
Mirault et al. Metallothionein expression in neurodegenerative diseases (1999). 1999. ↩︎
West et al. Argonaute proteins in RNA interference (2004). 2004. ↩︎
Iwasaki et al. Argonaute function in the nervous system (2015). 2015. ↩︎