deps-1

UniProt ID: Q9N303
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

DEPS-1 (DEfective P granules and Sterile) is a scaffold protein essential for P granule assembly and integrity in C. elegans germ cells. It functions as a key component of the P-granule assembly pathway, required for proper localization of PGL-1 and accumulation of GLH-1. DEPS-1 is also essential for RNA interference (RNAi) in the germline, particularly for piRNA-mediated gene silencing, where it directly interacts with the Argonaute protein PRG-1 and promotes formation of secondary 22G-RNAs (endo-siRNAs). The protein plays roles in germ cell proliferation, fertility, and small RNA-directed transgenerational epigenetic inheritance.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0031047 regulatory ncRNA-mediated gene silencing
IEA
GO_REF:0000043
ACCEPT
Summary: DEPS-1 is involved in multiple ncRNA-mediated gene silencing pathways. It is required for RNAi of germline-expressed genes and specifically for piRNA gene silencing (PMID:18234720, PMID:32843637). DEPS-1 promotes accumulation of RDE-4 (a dsRNA-binding protein required for RNAi) and positively regulates formation of secondary 22G-RNAs, which are endo-siRNAs.
Reason: This annotation correctly captures a core function of DEPS-1. The gene is required for RNA interference in the germline, promoting accumulation of RDE-4 and regulating endo-siRNA production (PMID:18234720). Additionally, DEPS-1 is essential for piRNA-mediated silencing through its interaction with PRG-1 (PMID:32843637). While GO:0031047 is a broad term, it accurately encompasses DEPS-1's role in both RNAi and piRNA pathways.
Supporting Evidence:
PMID:18234720
DEPS-1 is required for RNA interference (RNAi) of germline-expressed genes, possibly because DEPS-1 promotes the accumulation of RDE-4, a dsRNA-binding protein required for RNAi.
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 is **not required for primary piRNA (21U) abundance**, but is required for **piRNA-dependent silencing** through effects on secondary siRNAs
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 acts primarily **downstream of primary piRNA biogenesis**, promoting effective **piRNA-dependent silencing** through effects on **secondary 22G RNAs** and condensate organization
file:worm/deps-1/deps-1-deep-research-falcon.md
Spike et al. provide evidence that DEPS-1 promotes accumulation of **rde-4 mRNA and RDE-4 protein**, a dsRNA-binding factor essential for RNAi
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: DEPS-1 localizes to the perinuclear region of cytoplasm where P granules are found. It co-localizes with PRG-1 at peri-nuclear P-granules in the proliferative zone, transition zone, at pachytene, in oocytes and in embryos (PMID:32843637).
Reason: This annotation is correct but less specific than GO:0043186 (P granule). P granules are located at the perinuclear region of the cytoplasm, so this annotation is technically correct. However, the IDA annotation to GO:0043186 provides more specific localization information. This IEA annotation can be retained as it accurately reflects the general subcellular localization derived from UniProt annotation.
Supporting Evidence:
PMID:18234720
We have identified a new P-granule-associated protein, DEPS-1
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 and PRG-1 co-localize in **perinuclear granules** across multiple germline regions (proliferative zone to pachytene, oocytes, embryos)
GO:0043186 P granule
IDA
PMID:18234720
DEPS-1 promotes P-granule assembly and RNA interference in C...
ACCEPT
Summary: DEPS-1 localizes to P granules in germ cells at all stages of development. Direct experimental evidence from immunofluorescence studies demonstrates DEPS-1 localization to P granules (PMID:18234720). Additional studies confirm co-localization with PRG-1 at peri-nuclear P-granules and with PGL-1 in the pachytene region (PMID:32843637).
Reason: This is a well-supported IDA annotation based on direct localization studies. PMID:18234720 identified DEPS-1 as a P-granule-associated protein through immunofluorescence experiments. This is a core annotation for the gene, as P granule localization is essential for DEPS-1 function.
Supporting Evidence:
PMID:18234720
We have identified a new P-granule-associated protein, DEPS-1
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1::GFP is cytoplasmic and enriched on P granules, and anti-DEPS-1 staining of P granules is lost in deps-1 mutants
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 condensates appear as **small protein clusters localized within protein-dense P granules**
GO:1903863 P granule assembly
IMP
PMID:18234720
DEPS-1 promotes P-granule assembly and RNA interference in C...
NEW
Summary: DEPS-1 is required for P granule assembly and integrity. Loss of DEPS-1 disrupts P-granule structure, prevents proper PGL-1 localization to P granules, and reduces GLH-1 accumulation (PMID:18234720). DEPS-1 acts as a scaffold protein in the P-granule assembly pathway.
Reason: This annotation should be added based on functional evidence from PMID:18234720. The publication demonstrates that DEPS-1 loss-of-function disrupts P granule structure and composition, indicating a direct role in P granule assembly. This is a core function of the gene.
Supporting Evidence:
PMID:18234720
DEPS-1 promotes P-granule assembly... the loss of which disrupts P-granule structure and function. DEPS-1 is required for the proper localization of PGL-1 to P granules, the accumulation of glh-1 mRNA and protein
file:worm/deps-1/deps-1-deep-research-falcon.md
Loss-of-function deps-1 mutations disrupt the localization of **PGL-1** (and PGL-3) to P granules, consistent with DEPS-1 acting **upstream of PGL proteins** in a P-granule formation pathway
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 is a **constitutive P-granule component**
GO:0036093 germ cell proliferation
IMP
PMID:18234720
DEPS-1 promotes P-granule assembly and RNA interference in C...
NEW
Summary: deps-1 mutants show underproliferated germlines and fail to produce oocytes and sperm at restrictive temperatures, indicating a role in germ cell proliferation (PMID:18234720).
Reason: This annotation should be added as DEPS-1 is required for germ cell proliferation. The deps-1 mutant phenotype includes underproliferated germlines and sterility at elevated temperatures, demonstrating involvement in this biological process.
Supporting Evidence:
PMID:18234720
DEPS-1 is required for... germ cell proliferation and fertility at elevated temperatures.
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 is required for normal germline development and fertility, with a **maternal-effect and temperature-sensitive sterility phenotype**
GO:0140693 molecular condensate scaffold activity
NAS NEW
Summary: DEPS-1 functions as a non-enzymatic germline-specific condensate scaffold/adaptor that organizes perinuclear germ granules and couples them to small-RNA effector pathways. It directly binds the PRG-1 PIWI domain via an N-terminal PIWI-binding site (PBS) motif, and PBS deletion disperses DEPS-1 into the cytoplasm and disrupts higher-order organization of PRG-1/DEPS-1 condensates, demonstrating its scaffolding role.
Reason: Core function term not present in existing_annotations. The falcon deep research synthesis supports a non-enzymatic condensate scaffold/adaptor role: DEPS-1 lacks canonical RNA-binding motifs and instead organizes condensate architecture and couples P granules to PIWI/mutator machinery.
Supporting Evidence:
file:worm/deps-1/deps-1-deep-research-falcon.md
the evidence supports annotating DEPS-1 as a **non-enzymatic, germline-specific condensate scaffold/adaptor** that organizes perinuclear germ granules and couples them to small-RNA effector pathways
file:worm/deps-1/deps-1-deep-research-falcon.md
Deletion of PBS disperses DEPS-1 into the cytoplasm and disrupts higher-order organization of PRG-1/DEPS-1 condensates
file:worm/deps-1/deps-1-deep-research-falcon.md
DEPS-1 binds the **PRG-1 PIWI domain**, mediated by an N-terminal **PIWI-binding site (PBS)** motif

Core Functions

DEPS-1 functions as a scaffold protein for P granule assembly, organizing the liquid-like condensate structure of P granules in C. elegans germ cells. It is required for proper localization of PGL-1 and accumulation of GLH-1, acting as a core structural component of these ribonucleoprotein granules.

Supporting Evidence:
  • PMID:18234720
    We have identified a new P-granule-associated protein, DEPS-1, the loss of which disrupts P-granule structure and function. DEPS-1 is required for the proper localization of PGL-1 to P granules, the accumulation of glh-1 mRNA and protein.
  • file:worm/deps-1/deps-1-deep-research-falcon.md
    the evidence supports annotating DEPS-1 as a **non-enzymatic, germline-specific condensate scaffold/adaptor** that organizes perinuclear germ granules and couples them to small-RNA effector pathways

References

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells.
  • DEPS-1 is a novel P-granule-associated protein required for P granule structure and function
    "We have identified a new P-granule-associated protein, DEPS-1, the loss of which disrupts P-granule structure and function."
  • DEPS-1 is required for proper localization of PGL-1 to P granules
    "DEPS-1 is required for the proper localization of PGL-1 to P granules"
  • DEPS-1 promotes accumulation of glh-1 mRNA and protein
    "DEPS-1 is required for... the accumulation of glh-1 mRNA and protein"
  • DEPS-1 is required for germ cell proliferation and fertility at elevated temperatures
    "DEPS-1 is required for... germ cell proliferation and fertility at elevated temperatures"
  • DEPS-1 is required for RNAi of germline-expressed genes
    "DEPS-1 is required for RNA interference (RNAi) of germline-expressed genes"
  • DEPS-1 promotes accumulation of RDE-4, a dsRNA-binding protein required for RNAi
    "DEPS-1 promotes the accumulation of RDE-4, a dsRNA-binding protein required for RNAi"
DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans.
  • DEPS-1 directly interacts with PRG-1 (Piwi Argonaute) via its N-terminus
  • DEPS-1 is required for piRNA-mediated gene silencing
  • DEPS-1 positively regulates formation of secondary 22G-RNAs (endo-siRNAs)
  • DEPS-1 co-localizes with PRG-1 at peri-nuclear P-granules
A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans.
  • DEPS-1 plays a role in small RNA-directed transgenerational epigenetic inheritance
Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance.
  • deps-1 mutants have smaller Z granules (liquid-like condensates)
  • DEPS-1 is required for proper binding of ZNFX-1 to RNA
file:worm/deps-1/deps-1-deep-research-falcon.md
Falcon deep research report on C. elegans deps-1 (Q9N303)
  • DEPS-1 is a constitutive P-granule component that is cytoplasmic and enriched on P granules; antibody P-granule staining is lost in deps-1 mutants.
    "DEPS-1 is a **constitutive P-granule component**: DEPS-1::GFP is cytoplasmic and enriched on P granules, and anti-DEPS-1 staining of P granules is lost in deps-1 mutants"
  • DEPS-1 acts upstream of PGL-1/PGL-3 in P-granule assembly; loss of DEPS-1 disrupts PGL localization to P granules.
    "Loss-of-function deps-1 mutations disrupt the localization of **PGL-1** (and PGL-3) to P granules, consistent with DEPS-1 acting **upstream of PGL proteins** in a P-granule formation pathway"
  • DEPS-1 directly binds the PRG-1 PIWI domain via an N-terminal PIWI-binding site (PBS) motif; deletion of the PBS disperses DEPS-1 into the cytoplasm and disrupts higher-order PRG-1/DEPS-1 condensate organization.
    "DEPS-1 binds the **PRG-1 PIWI domain**, mediated by an N-terminal **PIWI-binding site (PBS)** motif (suen2020deps1isrequired pages 4-5)."
  • Microscale thermophoresis measured the DEPS-1/PRG-1 interaction with full-length affinity Kdapp = 855 +/- 133 nM and PBS-peptide affinity Kdapp = 1.9 uM +/- 98 nM.
    "Full-length PRG-1 vs full-length DEPS-1: **Kdapp = 855 ± 133 nM**"
  • DEPS-1 is not required for primary piRNA (21U) abundance but is required for piRNA-dependent silencing, acting downstream of PRG-1 to promote secondary 22G endo-siRNAs (notably for WAGO-class targets).
    "DEPS-1 is **not required for primary piRNA (21U) abundance**, but is required for **piRNA-dependent silencing** through effects on secondary siRNAs"
  • DEPS-1 promotes accumulation of rde-4 mRNA and RDE-4 protein, linking DEPS-1 to germline RNAi competence.
    "Spike et al. provide evidence that DEPS-1 promotes accumulation of **rde-4 mRNA and RDE-4 protein**, a dsRNA-binding factor essential for RNAi"
  • DEPS-1 organizes PRG-1 condensate morphology and maintains coupling between P granules and mutator foci; loss of DEPS-1 or the PBS yields fewer, brighter MUT-16 foci.
    "deps-1 loss or PBS mutation results in **fewer, brighter MUT-16 foci**"
  • Synthesis: DEPS-1 is best annotated as a non-enzymatic, germline-specific condensate scaffold/adaptor that organizes perinuclear germ granules and couples them to small-RNA effector pathways.
    "the evidence supports annotating DEPS-1 as a **non-enzymatic, germline-specific condensate scaffold/adaptor** that organizes perinuclear germ granules and couples them to small-RNA effector pathways"

Tags

caeel-p-granules

Deep Research

Falcon

(deps-1-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 7 citations 2 artifacts 2026-05-30T10:46:56.615901

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.

Research report: C. elegans deps-1 (UniProt Q9N303) — functional annotation and current evidence

Scope and identity verification

The target protein is DEPS-1 (defective P granules and sterile protein deps-1) from Caenorhabditis elegans, encoded by deps-1 / ORF Y65B4BL.2. Spike et al. mapped the phenotype to Y65B4BL.2, showed that RNAi of Y65B4BL.2 phenocopied deps-1 mutants, and detected allele-specific lesions in independent deps-1 alleles, verifying gene identity (spike2008deps1promotespgranule pages 4-5). DEPS-1 is described experimentally as a novel ~69 kDa protein with a serine-rich low-complexity C-terminus, lacking obvious canonical RNA-binding motifs, and conserved in related Caenorhabditis species (spike2008deps1promotespgranule pages 4-5).

1) Key concepts and definitions (current understanding)

P granules and perinuclear germ granule architecture

P granules are germline-specific ribonucleoprotein condensates (a type of membraneless organelle) that localize to the cytoplasmic face of germline nuclei and concentrate factors involved in post-transcriptional regulation and small-RNA-based genome surveillance. DEPS-1 is a constitutive P-granule component: DEPS-1::GFP is cytoplasmic and enriched on P granules, and anti-DEPS-1 staining of P granules is lost in deps-1 mutants (while nuclear staining persists, consistent with antibody cross-reactivity) (spike2008deps1promotespgranule pages 4-5).

Small RNA pathways linked to DEPS-1

DEPS-1 connects P granules to multiple germline small-RNA pathways, most notably:
- piRNA (21U RNA) pathway: PRG-1 (a PIWI Argonaute) binds 21U RNAs to recognize targets.
- Secondary endo-siRNA (22G RNA) pathways: RdRP-generated 22G RNAs amplify silencing and are associated with mutator machinery.
Mechanistically, DEPS-1 acts primarily downstream of primary piRNA biogenesis, promoting effective piRNA-dependent silencing through effects on secondary 22G RNAs and condensate organization (suen2020deps1isrequired pages 8-9).

2) Core functions, biological processes, and phenotypes (primary evidence)

A. P-granule assembly and organization

Loss-of-function deps-1 mutations disrupt the localization of PGL-1 (and PGL-3) to P granules, consistent with DEPS-1 acting upstream of PGL proteins in a P-granule formation pathway (spike2008deps1promotespgranule pages 4-5). This places DEPS-1 among the structural/organizational factors needed to assemble normal P-granule protein composition.

B. Germ cell proliferation, gametogenesis, and fertility

DEPS-1 is required for normal germline development and fertility, with a maternal-effect and temperature-sensitive sterility phenotype:
- In deps-1(bn121) M−Z− animals raised at 24.5°C, 93% are sterile (spike2008deps1promotespgranule pages 4-5).
- Germlines frequently lack gametes and have reduced germ cell numbers: 56% of germline arms had <200 germ nuclei (n=48), and 63% lacked both sperm and oocytes (spike2008deps1promotespgranule pages 4-5).
- Mean germ cells per gonad arm at 24.5°C: 254 ± 236 (n=16, range 10–762) vs wild-type 586 ± 45 (n=6, range 526–651) (spike2008deps1promotespgranule pages 4-5).
These data support DEPS-1 as a core germline integrity factor, likely through maintaining P-granule-dependent RNA regulation.

C. Germline RNA interference (RNAi) competence via RDE-4 accumulation

Spike et al. provide evidence that DEPS-1 promotes accumulation of rde-4 mRNA and RDE-4 protein, a dsRNA-binding factor essential for RNAi:
- rde-4 mRNA reduced 7–10-fold in deps-1 gravid adults (M−Z−) (spike2008deps1promotespgranule pages 7-8).
- RDE-4 protein reduced by ~10-fold in deps-1 M−Z− adults (spike2008deps1promotespgranule pages 7-8).
Consistent with this, deps-1 mutants are resistant to germline RNAi against maternally expressed genes such as pos-1, skn-1, pie-1, while RNAi against several zygotically expressed targets was not obviously altered (spike2008deps1promotespgranule pages 7-8). This supports a model in which DEPS-1 influences RNAi competence at least partly indirectly via maintaining RDE-4 levels.

3) Molecular mechanism: localization and interaction network

Subcellular localization

  • Adult germ line / embryos: DEPS-1 is cytoplasmic and concentrates on P granules; nuclear GFP is not observed in DEPS-1::GFP animals (spike2008deps1promotespgranule pages 4-5).
  • Perinuclear condensate substructure: DEPS-1 and PRG-1 co-localize in perinuclear granules across multiple germline regions (proliferative zone to pachytene, oocytes, embryos) (suen2020deps1isrequired pages 3-4). This co-localization is also visible in extracted Figure 1 panels (suen2020deps1isrequired media a9234a31).

Direct binding to PRG-1 via a PIWI-binding site (PBS)

Suen et al. show DEPS-1 physically couples the P granule scaffold to PIWI:
- DEPS-1 binds the PRG-1 PIWI domain, mediated by an N-terminal PIWI-binding site (PBS) motif (suen2020deps1isrequired pages 4-5).
- Microscale thermophoresis (MST) binding affinities:
- Full-length PRG-1 vs full-length DEPS-1: Kdapp = 855 ± 133 nM (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired media a9234a31).
- PBS peptide vs PRG-1 PIWI domain: Kdapp = 1.9 µM ± 98 nM (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired media a9234a31).
Deletion of PBS disperses DEPS-1 into the cytoplasm and disrupts higher-order organization of PRG-1/DEPS-1 condensates (suen2020deps1isrequired pages 3-4).

Condensate ultrastructure and coupling to mutator foci

DEPS-1 contributes to condensate morphology and links piRNA recognition to downstream amplification:
- Removing PBS compacts PRG-1 condensates; PRG-1/DEPS-1 normally form intertwining clusters to build elongated perinuclear condensates (suen2020deps1isrequired pages 3-4).
- deps-1 loss or PBS mutation results in fewer, brighter MUT-16 foci and altered PRG-1 condensate properties, consistent with disruption of the interface between P granules and mutator foci (suen2020deps1isrequired pages 9-10).

4) Pathway placement: piRNA-dependent silencing and 22G secondary siRNAs

DEPS-1 is not required for primary piRNA (21U) abundance, but is required for piRNA-dependent silencing through effects on secondary siRNAs:
- In deps-1 mutants, 21U levels remain similar to wild type, while prg-1 mutants show strong loss of 21Us (one-sided t-test p < 10−20, n=2) (suen2020deps1isrequired pages 8-9).
- deps-1 affects secondary 22G siRNAs across pathways, with a strong effect on WAGO-class targets:
- 300/425 WAGO targets show >2-fold reduction in 22Gs (hypergeometric p < 10−139) (suen2020deps1isrequired pages 8-9).
- Limited effect on ERGO-1 targets (7/23, p < 0.2) (suen2020deps1isrequired pages 8-9).
- For CSR-1 class, overlap with strong reductions is limited (e.g., 4/162 CSR-1 targets among genes with >2-fold 22G reduction; hypergeometric p < 10−13) (suen2020deps1isrequired pages 8-9).
- A global statistic reported: 8986/11,088 germline-expressed genes are endo-siRNA targets; 55/63 curated P-granule factors are endo-siRNA targets; and 10/63 P-granule factors show differential 22Gs in deps-1 mutant (suen2020deps1isrequired pages 9-10).
- Correlation between small RNA depletion and mRNA increase: when small RNAs decrease, target mRNAs tend to be upregulated (R² = 0.58; p < 0.01) (suen2020deps1isrequired pages 8-9).

Functionally, deps-1 mutants and PBS-deletion mutants desilence a piRNA sensor transgene, demonstrating a direct impact on piRNA-mediated repression in vivo (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired media a9234a31).

5) Recent developments (prioritizing 2023–2024)

2023: Expansion microscopy resolves DEPS-1 clusters and P-granule subdomains

A major recent technical advance directly involving DEPS-1 is the application of pan-protein staining with ~3× expansion microscopy (EExM) to resolve germ-granule subdomains:
- DEPS-1 condensates appear as small protein clusters localized within protein-dense P granules (suen2023expansionmicroscopyreveals pages 11-15).
- Quantitative granule counts per nucleus: 2.5 ± 0.8 (GFP-DEPS-1-positive granules) vs 2.8 ± 1.3 (pan-stain-positive granules), based on 9 nuclei from 3 experiments (suen2023expansionmicroscopyreveals pages 11-15).
- deps-1(bn124) mutants show fewer perinuclear protein-dense structures and can show PRG-1–containing granules dissociated from the nuclear membrane; P granule size is reduced in deps-1 and mut-16 mutants compared with wild type with reported significance (p < 0.001; p < 0.0001*) (suen2023expansionmicroscopyreveals pages 11-15).
This work reinforces the concept that germ granules are not homogeneous droplets but contain spatially organized subdomains, and provides an implementable quantitative pipeline for granule morphology analysis.

2024: Limited DEPS-1-specific extractable evidence in retrieved sources

A 2024 bioRxiv preprint was retrieved that mentions DEPS-1 in passing in the snippet returned by search; however, in the accessible extracted sections here, no interpretable DEPS-1-specific experimental evidence was available for extraction, so it is not used to support new DEPS-1 claims in this report.

6) Current applications and real-world implementations

Research groups actively use deps-1 and DEPS-1-based tools to interrogate germline condensates and small-RNA silencing:
1. piRNA sensor transgenes (H2B reporter with a piRNA target site) to assay defects in piRNA silencing; deps-1 null and ΔPBS mutants desilence this sensor (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired media a9234a31).
2. CRISPR/Cas9 motif editing of DEPS-1 (PBS deletion/replacement) to separate “presence in P granules” from “PIWI binding,” enabling causal tests of condensate organization vs silencing output (suen2020deps1isrequired pages 4-5).
3. Quantitative microscopy pipelines (e.g., expansion microscopy with pan-protein staining) for nanoscale mapping of DEPS-1 within perinuclear protein-dense structures and for measuring mutant effects on granule size and nuclear-envelope association (suen2023expansionmicroscopyreveals pages 11-15).
4. Germline RNAi competence assays using feeding RNAi against maternal genes, leveraging the RDE-4 dependency and deps-1-specific RNAi resistance phenotypes (spike2008deps1promotespgranule pages 7-8).

7) Expert interpretation and synthesis (evidence-based analysis)

Taken together, the evidence supports annotating DEPS-1 as a non-enzymatic, germline-specific condensate scaffold/adaptor that organizes perinuclear germ granules and couples them to small-RNA effector pathways.

Mechanistically, DEPS-1 appears to provide two separable but linked functions:
1. P-granule assembly/maintenance via upstream effects on PGL protein localization and on accumulation of other P-granule factors (e.g., GLH-1) (spike2008deps1promotespgranule pages 4-5).
2. piRNA pathway coupling via a direct DEPS-1–PRG-1 interaction (PBS–PIWI binding) that supports proper PRG-1 condensate ultrastructure and promotes downstream 22G siRNA amplification required for effective silencing (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired pages 8-9).

A consistent theme is that DEPS-1 loss perturbs both granule composition/architecture and small-RNA output, implying a functional relationship between condensate ultrastructure and biochemical throughput of gene-silencing reactions.

Summary evidence table

Finding Function/process Localization Interactions/partners Assays/evidence type Quantitative stats Primary source (date, URL)
Gene identity and core granule role DEPS-1 is the product of deps-1 / Y65B4BL.2, a constitutive P-granule-associated protein required for proper PGL-1/PGL-3 localization and thus P-granule assembly Cytoplasmic in germ cells and concentrated on P granules in adult germ line and late embryos; antibody P-granule staining lost in deps-1 mutants Genetic/functional relationship upstream of PGL-1/PGL-3; also influences GLH-1 accumulation Positional cloning/rescue, RNAi phenocopy, anti-DEPS-1 immunostaining, DEPS-1::GFP imaging, western blot DEPS-1 protein ~69 kDa; orthologs show 45–51% identity in related Caenorhabditis spp.; 4 mutant alleles predicted strong LOF/null Spike et al., “DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells” (Mar 2008), Development. https://doi.org/10.1242/dev.015552
Fertility and germ-cell proliferation phenotype DEPS-1 is required for fertility, gametogenesis, and normal germ-cell proliferation Germ line / gonad arms Linked functionally to constitutive P-granule machinery Mutant phenotype scoring, germ-cell counting, temperature-shift analysis In deps-1(bn121) M−Z− at 24.5°C, 93% sterile; 56% of germline arms had <200 germ nuclei; 63% lacked both sperm and oocytes; mean germ cells/gonad arm 254 ± 236 (n=16, range 10–762) vs wild type 586 ± 45 (n=6, range 526–651) Spike et al., 2008 (Mar 2008), Development. https://doi.org/10.1242/dev.015552
Germline RNAi support via RDE-4 DEPS-1 promotes germline RNA interference, likely in part by supporting rde-4 mRNA/protein accumulation; RNAi defects are selective for germline/maternal targets Germline P granules; post-transcriptional role inferred from cytoplasmic granule localization Functional link to RDE-4; overlap with RDE-3/MUT-2-repressed gene sets qRT-PCR, western blot, feeding RNAi assays, microarray comparison rde-4 mRNA reduced 7–10-fold and RDE-4 protein ~10-fold lower in deps-1 M−Z− adults; strong resistance to pos-1/skn-1/pie-1 RNAi; overlap of upregulated genes with rde-3 dataset: 9/32 (~30%), P < 2.2 × 10⁻⁹; selected genes upregulated ~4- to 326-fold Spike et al., 2008 (Mar 2008), Development. https://doi.org/10.1242/dev.015552
Direct PRG-1 binding and piRNA-silencing role DEPS-1 directly couples P granules to the piRNA pathway; required for piRNA-dependent silencing but not primary piRNA biogenesis Perinuclear granules across adult germline regions; DEPS-1 and PRG-1 form intertwined elongated condensates Direct interaction with PRG-1/PIWI via N-terminal PBS (PIWI-binding site) motif PRG-1 IP-MS, colocalization imaging, MST biophysics, CRISPR PBS deletion, piRNA sensor assay PRG-1 IP-MS recovered 133 proteins, DEPS-1 among top 10 interactors; MST Kdapp = 855 ± 133 nM (full-length PRG-1–DEPS-1), 349 ± 45 nM (PRG-1 PIWI–full-length DEPS-1), 1.9 µM ± 98 nM (PBS peptide–PRG-1 PIWI); deps-1 null and ΔPBS mutants desilence piRNA sensor Suen et al., “DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans” (Aug 2020), Nature Communications. https://doi.org/10.1038/s41467-020-18089-1
Condensate ultrastructure and mutator-foci coupling DEPS-1 organizes PRG-1 condensate morphology and helps maintain spatial coupling between P granules and mutator foci for downstream silencing Perinuclear P granules; loss of PBS causes DEPS-1 cytoplasmic diffusion and compacted PRG-1 condensates PRG-1, MUT-16, additional interactor EDG-1 Live imaging, high-resolution microscopy, condensate morphometry, Y2H for EDG-1 ΔPBS protein expressed at ~70% of WT; PRG-1 condensates become more compacted in deps-1 null/ΔPBS; PRG-1 morphometry sampled 20 condensates from 2 germlines (n=40 per genotype); deps-1 mutants show fewer, brighter MUT-16 foci; edg-1 knockdown specifically alters DEPS-1 condensates Suen et al., 2020 (Aug 2020), Nature Communications. https://doi.org/10.1038/s41467-020-18089-1
Secondary endo-siRNA / 22G homeostasis DEPS-1 acts downstream of PRG-1 to promote secondary 22G endo-siRNAs from piRNA targets and affects multiple germline small-RNA pathways Functional bridge between P granules and mutator foci PRG-1-associated piRNA pathway; effects on WAGO, limited on ERGO-1, modest/complex on CSR-1 classes Small-RNA sequencing, enrichment/overlap analyses, reporter silencing 21U/piRNA levels remain similar to WT in deps-1 mutants, whereas prg-1 loses 21Us (one-sided t-test P < 10⁻²⁰, n=2); 300/425 WAGO targets show >2-fold 22G reduction (P < 10⁻¹³⁹); 7/23 ERGO-1 targets affected (P < 0.2); overlap with reduced CSR-1-target 22Gs 4/162 genes vs 447/2012 genes with >2-fold reduction (P < 10⁻¹³); sequencing often n=3 biological replicates Suen et al., 2020 (Aug 2020), Nature Communications. https://doi.org/10.1038/s41467-020-18089-1
Small RNAs target granule genes and explain transcript effects DEPS-1 perturbation changes endo-siRNAs targeting granule factors and correlates with mRNA changes Germline perinuclear granule system Endo-siRNA targeting of P-granule factors broadly Integrative analysis of small RNA and prior expression data 8986/11,088 germline-expressed genes are endo-siRNA targets; 55/63 curated P-granule factors are endo-siRNA targets; 10/63 P-granule factors show differential 22Gs in deps-1 mutant; decrease in small RNAs correlates with mRNA increase (R² = 0.58, P < 0.01) Suen et al., 2020 (Aug 2020), Nature Communications. https://doi.org/10.1038/s41467-020-18089-1
Recent nanoscale localization update 2023 expansion microscopy refines DEPS-1 placement within protein-dense P granules and shows P granule malformation in deps-1 mutants DEPS-1 appears as small clusters localized within P granules; deps-1 mutants show reduced and sometimes nuclear-membrane-dissociated perinuclear granules Spatial comparison with PRG-1, MUT-16, ZNFX-1 subdomains Expansion microscopy (EExM), pan-protein staining, anti-DEPS-1/PRG-1 imaging, granule-size normalization Average granules per nucleus: 2.5 ± 0.8 by GFP-DEPS-1 and 2.8 ± 1.3 by pan-stain (9 nuclei, 3 experiments); average expansion factor ~3× from 31 expanded nuclei / 6 experiments vs 47 non-expanded nuclei / 3 experiments; P granules smaller in deps-1(bn124) and mut-16(pk710), with significance P < 0.001 and P < 0.0001 depending on comparison Suen et al., “Expansion microscopy reveals subdomains in C. elegans germ granules” (May 2023 preprint), bioRxiv. https://doi.org/10.1101/2022.05.29.493872

Table: This table summarizes core experimental findings for C. elegans DEPS-1, including function, localization, molecular partners, assay types, and quantitative results from the main primary studies. It is designed as a compact evidence map for functional annotation of UniProt Q9N303.

Key quantitative highlights (selected)

  • Sterility: 93% sterile in deps-1(bn121) M−Z− at 24.5°C (spike2008deps1promotespgranule pages 4-5).
  • Germ cell counts: 254 ± 236 (deps-1) vs 586 ± 45 (WT) germ cells per gonad arm at 24.5°C (spike2008deps1promotespgranule pages 4-5).
  • RDE-4: rde-4 mRNA 7–10× reduced; RDE-4 protein ~10× reduced in deps-1 M−Z− adults (spike2008deps1promotespgranule pages 7-8).
  • DEPS-1–PRG-1 binding: Kdapp 855 ± 133 nM (full-length); Kdapp 1.9 µM ± 98 nM (PBS peptide–PIWI) (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired media a9234a31).
  • Small RNA effects: 300/425 WAGO targets with >2-fold 22G reduction (p < 10−139); 8986/11,088 germline genes targeted by endo-siRNAs (suen2020deps1isrequired pages 8-9, suen2020deps1isrequired pages 9-10).
  • 2023 subdomain quantification: granules/nucleus 2.5 ± 0.8 by GFP-DEPS-1 vs 2.8 ± 1.3 by pan-stain; reduced P-granule size in deps-1 mutants with significant p-values (suen2023expansionmicroscopyreveals pages 11-15).

URLs and publication dates (primary sources used here)

  • Spike CA et al. 2008-03. “DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells.” Development. https://doi.org/10.1242/dev.015552 (spike2008deps1promotespgranule pages 4-5, spike2008deps1promotespgranule pages 7-8)
  • Suen KM et al. 2020-08. “DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans.” Nature Communications 11:4242. https://doi.org/10.1038/s41467-020-18089-1 (suen2020deps1isrequired pages 3-4, suen2020deps1isrequired pages 8-9)
  • Suen KM et al. 2023-05 (preprint). “Expansion microscopy reveals subdomains in C. elegans germ granules.” bioRxiv. https://doi.org/10.1101/2022.05.29.493872 (suen2023expansionmicroscopyreveals pages 11-15)

Limitations of this report

  • UniProt domain annotations (e.g., OB_DEPS-1 repeats) were provided by the user but not directly retrieved via tools in this run; domain-level mechanistic inference is therefore conservatively limited to what is supported by the primary papers retrieved here.
  • A 2024 preprint mentioning DEPS-1 was retrieved by title/snippet, but the accessible text chunks in this run did not yield DEPS-1-specific evidence suitable for citation; thus 2023 remains the most recent directly evidentiary DEPS-1 source in the tool-retrieved corpus.

References

  1. (spike2008deps1promotespgranule pages 4-5): Caroline A. Spike, Jason Bader, Valerie Reinke, and Susan Strome. Deps-1 promotes p-granule assembly and rna interference in c. elegans germ cells. Development, 135:983-993, Mar 2008. URL: https://doi.org/10.1242/dev.015552, doi:10.1242/dev.015552. This article has 98 citations and is from a domain leading peer-reviewed journal.

  2. (suen2020deps1isrequired pages 8-9): Kin Man Suen, Fabian Braukmann, Richard Butler, Dalila Bensaddek, Alper Akay, Chi-Chuan Lin, Dovilė Milonaitytė, Neel Doshi, Alexandra Sapetschnig, Angus Lamond, John Edward Ladbury, and Eric Alexander Miska. Deps-1 is required for pirna-dependent silencing and piwi condensate organisation in caenorhabditis elegans. Text, Aug 2020. URL: https://doi.org/10.17863/cam.74696, doi:10.17863/cam.74696. This article has 28 citations and is from a peer-reviewed journal.

  3. (spike2008deps1promotespgranule pages 7-8): Caroline A. Spike, Jason Bader, Valerie Reinke, and Susan Strome. Deps-1 promotes p-granule assembly and rna interference in c. elegans germ cells. Development, 135:983-993, Mar 2008. URL: https://doi.org/10.1242/dev.015552, doi:10.1242/dev.015552. This article has 98 citations and is from a domain leading peer-reviewed journal.

  4. (suen2020deps1isrequired pages 3-4): Kin Man Suen, Fabian Braukmann, Richard Butler, Dalila Bensaddek, Alper Akay, Chi-Chuan Lin, Dovilė Milonaitytė, Neel Doshi, Alexandra Sapetschnig, Angus Lamond, John Edward Ladbury, and Eric Alexander Miska. Deps-1 is required for pirna-dependent silencing and piwi condensate organisation in caenorhabditis elegans. Text, Aug 2020. URL: https://doi.org/10.17863/cam.74696, doi:10.17863/cam.74696. This article has 28 citations and is from a peer-reviewed journal.

  5. (suen2020deps1isrequired media a9234a31): Kin Man Suen, Fabian Braukmann, Richard Butler, Dalila Bensaddek, Alper Akay, Chi-Chuan Lin, Dovilė Milonaitytė, Neel Doshi, Alexandra Sapetschnig, Angus Lamond, John Edward Ladbury, and Eric Alexander Miska. Deps-1 is required for pirna-dependent silencing and piwi condensate organisation in caenorhabditis elegans. Text, Aug 2020. URL: https://doi.org/10.17863/cam.74696, doi:10.17863/cam.74696. This article has 28 citations and is from a peer-reviewed journal.

  6. (suen2020deps1isrequired pages 4-5): Kin Man Suen, Fabian Braukmann, Richard Butler, Dalila Bensaddek, Alper Akay, Chi-Chuan Lin, Dovilė Milonaitytė, Neel Doshi, Alexandra Sapetschnig, Angus Lamond, John Edward Ladbury, and Eric Alexander Miska. Deps-1 is required for pirna-dependent silencing and piwi condensate organisation in caenorhabditis elegans. Text, Aug 2020. URL: https://doi.org/10.17863/cam.74696, doi:10.17863/cam.74696. This article has 28 citations and is from a peer-reviewed journal.

  7. (suen2020deps1isrequired pages 9-10): Kin Man Suen, Fabian Braukmann, Richard Butler, Dalila Bensaddek, Alper Akay, Chi-Chuan Lin, Dovilė Milonaitytė, Neel Doshi, Alexandra Sapetschnig, Angus Lamond, John Edward Ladbury, and Eric Alexander Miska. Deps-1 is required for pirna-dependent silencing and piwi condensate organisation in caenorhabditis elegans. Text, Aug 2020. URL: https://doi.org/10.17863/cam.74696, doi:10.17863/cam.74696. This article has 28 citations and is from a peer-reviewed journal.

  8. (suen2023expansionmicroscopyreveals pages 11-15): Kin M. Suen, Thomas M. D. Sheard, Chi-Chuan Lin, Dovile Milonaityte, Izzy Jayasinghe, and John E. Ladbury. Expansion microscopy reveals subdomains in c. elegans germ granules. bioRxiv, May 2023. URL: https://doi.org/10.1101/2022.05.29.493872, doi:10.1101/2022.05.29.493872. This article has 6 citations.

Artifacts

Citations

  1. suen2023expansionmicroscopyreveals pages 11-15
  2. https://doi.org/10.1242/dev.015552
  3. https://doi.org/10.1038/s41467-020-18089-1
  4. https://doi.org/10.1101/2022.05.29.493872
  5. https://doi.org/10.1242/dev.015552,
  6. https://doi.org/10.17863/cam.74696,
  7. https://doi.org/10.1101/2022.05.29.493872,

📄 View Raw YAML

id: Q9N303
gene_symbol: deps-1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: 'DEPS-1 (DEfective P granules and Sterile) is a scaffold protein essential
  for P granule assembly and integrity in C. elegans germ cells. It functions as a
  key component of the P-granule assembly pathway, required for proper localization
  of PGL-1 and accumulation of GLH-1. DEPS-1 is also essential for RNA interference
  (RNAi) in the germline, particularly for piRNA-mediated gene silencing, where it
  directly interacts with the Argonaute protein PRG-1 and promotes formation of secondary
  22G-RNAs (endo-siRNAs). The protein plays roles in germ cell proliferation, fertility,
  and small RNA-directed transgenerational epigenetic inheritance.

  '
existing_annotations:
  - term:
      id: GO:0031047
      label: regulatory ncRNA-mediated gene silencing
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: 'DEPS-1 is involved in multiple ncRNA-mediated gene silencing pathways.
        It is required for RNAi of germline-expressed genes and specifically for piRNA
        gene silencing (PMID:18234720, PMID:32843637). DEPS-1 promotes accumulation
        of RDE-4 (a dsRNA-binding protein required for RNAi) and positively regulates
        formation of secondary 22G-RNAs, which are endo-siRNAs.

        '
      action: ACCEPT
      reason: 'This annotation correctly captures a core function of DEPS-1. The gene
        is required for RNA interference in the germline, promoting accumulation of
        RDE-4 and regulating endo-siRNA production (PMID:18234720). Additionally,
        DEPS-1 is essential for piRNA-mediated silencing through its interaction with
        PRG-1 (PMID:32843637). While GO:0031047 is a broad term, it accurately encompasses
        DEPS-1''s role in both RNAi and piRNA pathways.

        '
      additional_reference_ids:
        - file:worm/deps-1/deps-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:18234720
          supporting_text: DEPS-1 is required for RNA interference (RNAi) of
            germline-expressed genes, possibly because DEPS-1 promotes the
            accumulation of RDE-4, a dsRNA-binding protein required for RNAi.
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 is **not required for primary piRNA (21U) abundance**, but is
            required for **piRNA-dependent silencing** through effects on secondary
            siRNAs
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 acts primarily **downstream of primary piRNA biogenesis**,
            promoting effective **piRNA-dependent silencing** through effects on
            **secondary 22G RNAs** and condensate organization
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            Spike et al. provide evidence that DEPS-1 promotes accumulation of
            **rde-4 mRNA and RDE-4 protein**, a dsRNA-binding factor essential for
            RNAi
  - term:
      id: GO:0048471
      label: perinuclear region of cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: 'DEPS-1 localizes to the perinuclear region of cytoplasm where P granules
        are found. It co-localizes with PRG-1 at peri-nuclear P-granules in the proliferative
        zone, transition zone, at pachytene, in oocytes and in embryos (PMID:32843637).

        '
      action: ACCEPT
      reason: 'This annotation is correct but less specific than GO:0043186 (P granule).
        P granules are located at the perinuclear region of the cytoplasm, so this
        annotation is technically correct. However, the IDA annotation to GO:0043186
        provides more specific localization information. This IEA annotation can be
        retained as it accurately reflects the general subcellular localization derived
        from UniProt annotation.

        '
      additional_reference_ids:
        - file:worm/deps-1/deps-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:18234720
          supporting_text: We have identified a new P-granule-associated
            protein, DEPS-1
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 and PRG-1 co-localize in **perinuclear granules** across
            multiple germline regions (proliferative zone to pachytene, oocytes,
            embryos)
  - term:
      id: GO:0043186
      label: P granule
    evidence_type: IDA
    original_reference_id: PMID:18234720
    review:
      summary: 'DEPS-1 localizes to P granules in germ cells at all stages of development.
        Direct experimental evidence from immunofluorescence studies demonstrates
        DEPS-1 localization to P granules (PMID:18234720). Additional studies confirm
        co-localization with PRG-1 at peri-nuclear P-granules and with PGL-1 in the
        pachytene region (PMID:32843637).

        '
      action: ACCEPT
      reason: 'This is a well-supported IDA annotation based on direct localization
        studies. PMID:18234720 identified DEPS-1 as a P-granule-associated protein
        through immunofluorescence experiments. This is a core annotation for the
        gene, as P granule localization is essential for DEPS-1 function.

        '
      additional_reference_ids:
        - file:worm/deps-1/deps-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:18234720
          supporting_text: We have identified a new P-granule-associated
            protein, DEPS-1
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1::GFP is cytoplasmic and enriched on P granules, and
            anti-DEPS-1 staining of P granules is lost in deps-1 mutants
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 condensates appear as **small protein clusters localized
            within protein-dense P granules**
  - term:
      id: GO:1903863
      label: P granule assembly
    evidence_type: IMP
    original_reference_id: PMID:18234720
    review:
      summary: 'DEPS-1 is required for P granule assembly and integrity. Loss of DEPS-1
        disrupts P-granule structure, prevents proper PGL-1 localization to P granules,
        and reduces GLH-1 accumulation (PMID:18234720). DEPS-1 acts as a scaffold
        protein in the P-granule assembly pathway.

        '
      action: NEW
      reason: 'This annotation should be added based on functional evidence from PMID:18234720.
        The publication demonstrates that DEPS-1 loss-of-function disrupts P granule
        structure and composition, indicating a direct role in P granule assembly.
        This is a core function of the gene.

        '
      additional_reference_ids:
        - file:worm/deps-1/deps-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:18234720
          supporting_text: DEPS-1 promotes P-granule assembly... the loss of
            which disrupts P-granule structure and function. DEPS-1 is required
            for the proper localization of PGL-1 to P granules, the accumulation
            of glh-1 mRNA and protein
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            Loss-of-function deps-1 mutations disrupt the localization of
            **PGL-1** (and PGL-3) to P granules, consistent with DEPS-1 acting
            **upstream of PGL proteins** in a P-granule formation pathway
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 is a **constitutive P-granule component**
  - term:
      id: GO:0036093
      label: germ cell proliferation
    evidence_type: IMP
    original_reference_id: PMID:18234720
    review:
      summary: 'deps-1 mutants show underproliferated germlines and fail to produce
        oocytes and sperm at restrictive temperatures, indicating a role in germ cell
        proliferation (PMID:18234720).

        '
      action: NEW
      reason: 'This annotation should be added as DEPS-1 is required for germ cell
        proliferation. The deps-1 mutant phenotype includes underproliferated germlines
        and sterility at elevated temperatures, demonstrating involvement in this
        biological process.

        '
      additional_reference_ids:
        - file:worm/deps-1/deps-1-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:18234720
          supporting_text: DEPS-1 is required for... germ cell proliferation and
            fertility at elevated temperatures.
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 is required for normal germline development and fertility,
            with a **maternal-effect and temperature-sensitive sterility
            phenotype**
  - term:
      id: GO:0140693
      label: molecular condensate scaffold activity
    evidence_type: NAS
    review:
      summary: >-
        DEPS-1 functions as a non-enzymatic germline-specific condensate
        scaffold/adaptor that organizes perinuclear germ granules and couples
        them to small-RNA effector pathways. It directly binds the PRG-1 PIWI
        domain via an N-terminal PIWI-binding site (PBS) motif, and PBS deletion
        disperses DEPS-1 into the cytoplasm and disrupts higher-order
        organization of PRG-1/DEPS-1 condensates, demonstrating its scaffolding
        role.
      action: NEW
      reason: >-
        Core function term not present in existing_annotations. The falcon deep
        research synthesis supports a non-enzymatic condensate scaffold/adaptor
        role: DEPS-1 lacks canonical RNA-binding motifs and instead organizes
        condensate architecture and couples P granules to PIWI/mutator
        machinery.
      additional_reference_ids:
        - file:worm/deps-1/deps-1-deep-research-falcon.md
      supported_by:
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            the evidence supports annotating DEPS-1 as a **non-enzymatic,
            germline-specific condensate scaffold/adaptor** that organizes
            perinuclear germ granules and couples them to small-RNA effector
            pathways
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            Deletion of PBS disperses DEPS-1 into the cytoplasm and disrupts
            higher-order organization of PRG-1/DEPS-1 condensates
        - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
          supporting_text: >-
            DEPS-1 binds the **PRG-1 PIWI domain**, mediated by an N-terminal
            **PIWI-binding site (PBS)** motif
references:
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    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: PMID:18234720
    title: DEPS-1 promotes P-granule assembly and RNA interference in C. elegans
      germ cells.
    findings:
      - statement: DEPS-1 is a novel P-granule-associated protein required for P
          granule structure and function
        supporting_text: We have identified a new P-granule-associated protein, 
          DEPS-1, the loss of which disrupts P-granule structure and function.
      - statement: DEPS-1 is required for proper localization of PGL-1 to P 
          granules
        supporting_text: DEPS-1 is required for the proper localization of PGL-1
          to P granules
      - statement: DEPS-1 promotes accumulation of glh-1 mRNA and protein
        supporting_text: DEPS-1 is required for... the accumulation of glh-1 
          mRNA and protein
      - statement: DEPS-1 is required for germ cell proliferation and fertility 
          at elevated temperatures
        supporting_text: DEPS-1 is required for... germ cell proliferation and 
          fertility at elevated temperatures
      - statement: DEPS-1 is required for RNAi of germline-expressed genes
        supporting_text: DEPS-1 is required for RNA interference (RNAi) of 
          germline-expressed genes
      - statement: DEPS-1 promotes accumulation of RDE-4, a dsRNA-binding 
          protein required for RNAi
        supporting_text: DEPS-1 promotes the accumulation of RDE-4, a 
          dsRNA-binding protein required for RNAi
  - id: PMID:32843637
    title: DEPS-1 is required for piRNA-dependent silencing and PIWI condensate 
      organisation in Caenorhabditis elegans.
    findings:
      - statement: DEPS-1 directly interacts with PRG-1 (Piwi Argonaute) via its
          N-terminus
      - statement: DEPS-1 is required for piRNA-mediated gene silencing
      - statement: DEPS-1 positively regulates formation of secondary 22G-RNAs 
          (endo-siRNAs)
      - statement: DEPS-1 co-localizes with PRG-1 at peri-nuclear P-granules
  - id: PMID:27015309
    title: A Tunable Mechanism Determines the Duration of the Transgenerational 
      Small RNA Inheritance in C. elegans.
    findings:
      - statement: DEPS-1 plays a role in small RNA-directed transgenerational 
          epigenetic inheritance
  - id: PMID:29769721
    title: Spatiotemporal regulation of liquid-like condensates in epigenetic
      inheritance.
    findings:
      - statement: deps-1 mutants have smaller Z granules (liquid-like
          condensates)
      - statement: DEPS-1 is required for proper binding of ZNFX-1 to RNA
  - id: file:worm/deps-1/deps-1-deep-research-falcon.md
    title: Falcon deep research report on C. elegans deps-1 (Q9N303)
    findings:
      - statement: >-
          DEPS-1 is a constitutive P-granule component that is cytoplasmic and
          enriched on P granules; antibody P-granule staining is lost in deps-1
          mutants.
        supporting_text: >-
          DEPS-1 is a **constitutive P-granule component**: DEPS-1::GFP is
          cytoplasmic and enriched on P granules, and anti-DEPS-1 staining of P
          granules is lost in deps-1 mutants
      - statement: >-
          DEPS-1 acts upstream of PGL-1/PGL-3 in P-granule assembly; loss of
          DEPS-1 disrupts PGL localization to P granules.
        supporting_text: >-
          Loss-of-function deps-1 mutations disrupt the localization of
          **PGL-1** (and PGL-3) to P granules, consistent with DEPS-1 acting
          **upstream of PGL proteins** in a P-granule formation pathway
      - statement: >-
          DEPS-1 directly binds the PRG-1 PIWI domain via an N-terminal
          PIWI-binding site (PBS) motif; deletion of the PBS disperses DEPS-1
          into the cytoplasm and disrupts higher-order PRG-1/DEPS-1 condensate
          organization.
        supporting_text: >-
          DEPS-1 binds the **PRG-1 PIWI domain**, mediated by an N-terminal
          **PIWI-binding site (PBS)** motif (suen2020deps1isrequired pages
          4-5).
      - statement: >-
          Microscale thermophoresis measured the DEPS-1/PRG-1 interaction with
          full-length affinity Kdapp = 855 +/- 133 nM and PBS-peptide affinity
          Kdapp = 1.9 uM +/- 98 nM.
        supporting_text: >-
          Full-length PRG-1 vs full-length DEPS-1: **Kdapp = 855 ± 133 nM**
      - statement: >-
          DEPS-1 is not required for primary piRNA (21U) abundance but is
          required for piRNA-dependent silencing, acting downstream of PRG-1 to
          promote secondary 22G endo-siRNAs (notably for WAGO-class targets).
        supporting_text: >-
          DEPS-1 is **not required for primary piRNA (21U) abundance**, but is
          required for **piRNA-dependent silencing** through effects on secondary
          siRNAs
      - statement: >-
          DEPS-1 promotes accumulation of rde-4 mRNA and RDE-4 protein, linking
          DEPS-1 to germline RNAi competence.
        supporting_text: >-
          Spike et al. provide evidence that DEPS-1 promotes accumulation of
          **rde-4 mRNA and RDE-4 protein**, a dsRNA-binding factor essential for
          RNAi
      - statement: >-
          DEPS-1 organizes PRG-1 condensate morphology and maintains coupling
          between P granules and mutator foci; loss of DEPS-1 or the PBS yields
          fewer, brighter MUT-16 foci.
        supporting_text: >-
          deps-1 loss or PBS mutation results in **fewer, brighter MUT-16 foci**
      - statement: >-
          Synthesis: DEPS-1 is best annotated as a non-enzymatic,
          germline-specific condensate scaffold/adaptor that organizes
          perinuclear germ granules and couples them to small-RNA effector
          pathways.
        supporting_text: >-
          the evidence supports annotating DEPS-1 as a **non-enzymatic,
          germline-specific condensate scaffold/adaptor** that organizes
          perinuclear germ granules and couples them to small-RNA effector
          pathways
core_functions:
  - molecular_function:
      id: GO:0140693
      label: molecular condensate scaffold activity
    description: DEPS-1 functions as a scaffold protein for P granule assembly, 
      organizing the liquid-like condensate structure of P granules in C. 
      elegans germ cells. It is required for proper localization of PGL-1 and 
      accumulation of GLH-1, acting as a core structural component of these 
      ribonucleoprotein granules.
    directly_involved_in:
      - id: GO:1903863
        label: P granule assembly
      - id: GO:0031047
        label: regulatory ncRNA-mediated gene silencing
    locations:
      - id: GO:0043186
        label: P granule
      - id: GO:0048471
        label: perinuclear region of cytoplasm
    supported_by:
      - reference_id: PMID:18234720
        supporting_text: We have identified a new P-granule-associated protein,
          DEPS-1, the loss of which disrupts P-granule structure and function.
          DEPS-1 is required for the proper localization of PGL-1 to P granules,
          the accumulation of glh-1 mRNA and protein.
      - reference_id: file:worm/deps-1/deps-1-deep-research-falcon.md
        supporting_text: >-
          the evidence supports annotating DEPS-1 as a **non-enzymatic,
          germline-specific condensate scaffold/adaptor** that organizes
          perinuclear germ granules and couples them to small-RNA effector
          pathways
tags:
  - caeel-p-granules