| Property | Summary |
|---|---|
| Gene name | **wago-4**; ORF **F58G1.1**; encodes worm-specific Argonaute protein 4 in *Caenorhabditis elegans* (pqac-00000014, pqac-00000026) |
| UniProt ID | **O62275** (user-supplied target identifier; matches *C. elegans* WAGO-4 Argonaute context summarized in the cited literature) |
| Organism | **Caenorhabditis elegans** (pqac-00000003, pqac-00000014) |
| Protein family | Argonaute family, **WAGO subfamily**; one of the expanded nematode worm-specific Argonautes involved in endogenous and heritable RNA silencing (pqac-00000013, pqac-00000014, pqac-00000016) |
| Domain architecture | Canonical Argonaute architecture with **PAZ** and **PIWI** domains; WAGO proteins also show a divergent **HKQK** motif associated with 22G-RNA loading specificity rather than the canonical Argonaute catalytic configuration (pqac-00000019) |
| Subcellular localization | Germline **perinuclear granules**; localizes with **P granules** in early embryonic germline blastomeres, then demixes with ZNFX-1 into **Z granules**; in adults participates in ordered **PZM** assemblages with P granules and Mutator foci; loss of GLH FG repeats shifts WAGO-4 toward the **cytoplasm** (pqac-00000003, pqac-00000010, pqac-00000011, pqac-00000007, pqac-00000008, pqac-00000012) |
| Small RNA binding specificity | Binds **22G-RNAs**; literature supports association with **CSR-class 22G-RNAs** and also cross-loading/binding of **both CSR-class and WAGO-class 22G-RNAs** under wild-type conditions; proper granule localization helps preserve correct loading specificity (pqac-00000000, pqac-00000013, pqac-00000015, pqac-00000020, pqac-00000029, pqac-00000030) |
| Primary function | Cytoplasmic/heritable silencing Argonaute required for **RNAi inheritance** and **transgenerational epigenetic inheritance (TEI)**; acts with ZNFX-1 to mark target mRNAs and maintain heritable siRNA expression across generations (pqac-00000001, pqac-00000003, pqac-00000004) |
| Functional pathway context | Part of the germline 22G-RNA network and a **CSR-1/WAGO-4 regulatory hub**; helps coordinate post-transcriptional silencing and inherited small-RNA responses in germ granules/Z granules (pqac-00000017, pqac-00000000) |
| Key interaction partners | **ZNFX-1** (co-localized and cooperative factor in Z granules/TEI), **MINA-1** (physical and regulatory interactor that represses WAGO-4 expression), **CDE-1** (3' uridylation promotes WAGO-4 association with heritable small RNAs per review evidence), **GLH proteins** including GLH-1/4 FG repeats (promote granule partitioning), and **EGO-1** (proposed RdRP recruited in the inheritance pathway) (pqac-00000001, pqac-00000003, pqac-00000000, pqac-00000007, pqac-00000012, pqac-00000021, pqac-00000022, pqac-00000024) |
| Phenotypes of loss-of-function | **Heritable RNAi defective** phenotype; impaired transgenerational silencing/RNAi inheritance; altered endogenous target regulation; fertility defects and **Mortal Germline (Mrt)** phenotype are observed when WAGO-4 function or granule localization is compromised, especially at elevated temperature (pqac-00000000, pqac-00000001, pqac-00000028, pqac-00000032, pqac-00000033) |
| Phenotypes of mislocalization | Reduced enrichment in germ granules causes altered 22G-RNA loading, increased reliance on CSR-1-like targets, reduced regulation of WAGO-4-specific/piRNA- and MUT-16-dependent targets, and defective fertility/gene silencing fidelity (pqac-00000028, pqac-00000029, pqac-00000030, pqac-00000034) |
| Germline/apoptosis role | WAGO-4 also participates in a regulatory network with **MINA-1** that links RNAi machinery to **germ cell apoptosis**; elevated WAGO-4 in *mina-1* mutants increases RNAi sensitivity and germ cell death, while *wago-4* loss suppresses these phenotypes (pqac-00000021, pqac-00000022, pqac-00000023, pqac-00000024) |


*Table: This table summarizes the identity, localization, molecular associations, small-RNA specificity, and phenotypes of the *C. elegans* Argonaute WAGO-4. It is useful as a compact reference for functional annotation of UniProt O62275.*