wdr-23

UniProt ID: S6FN32
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

Caenorhabditis elegans wdr-23 (D2030.9) encodes a WD40-repeat DDB1- and CUL4-associated factor, the nematode ortholog of human DCAF11/WDR23 (PANTHER PTHR19847:SF7). WDR-23 is a non-catalytic substrate receptor of a CUL-4/DDB-1 cullin-RING ubiquitin ligase. It binds the cytoprotective transcription factor SKN-1 and restrains its abundance, nuclear accumulation and activity, so that loss of wdr-23 constitutively induces SKN-1-dependent detoxification and oxidative-stress genes; it also binds the Holliday junction resolvase GEN-1. The gene produces a cytoplasmic WDR-23A isoform (associated with mitochondria and presynaptic organelles in neurons) and a nuclear WDR-23B isoform that differ only in their N termini; nuclear WDR-23B provides the main negative, turnover-promoting control of SKN-1 and GEN-1, whereas WDR-23A has a proteasome-independent role. This entry, S6FN32, is the 498-residue D2030.9d gene model, which starts at an internal methionine (Met74 of WDR-23A) and lacks both isoform-specific N termini but retains all WD repeats and the WDxR DDB1-binding motifs; its expression and localization have not been examined directly.

Core Functions

Substrate receptor of the CUL-4/DDB-1 cullin-RING ubiquitin ligase: the WD40 propeller binds substrates (SKN-1, GEN-1) and WDxR motifs dock on DDB-1, so that substrates are presented for ubiquitination; nuclear action promotes substrate turnover. Asserted at gene level from the assayed WDR-23A/B products; S6FN32 retains the WD40 propeller and WDxR motifs but has not been assayed itself, and its compartment (and hence substrate outcome) is unresolved.

Molecular Function:
ubiquitin-like ligase-substrate adaptor activity
Directly Involved In:
proteasome-mediated ubiquitin-dependent protein catabolic process
In Complex:
Cul4-RING E3 ubiquitin ligase complex
Supporting Evidence:
  • PMID:19273594
    WDR-23, which interacts with the CUL-4/DDB-1 ubiquitin ligase
  • PMID:19273594
    SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23
  • PMID:31409866
    nuclear WDR-23B inhibits the activity of substrates, most likely by promoting protein turnover, while cytoplasmic WDR-23A performs a proteasome-independent role.
  • file:worm/wdr-23/wdr-23-bioinformatics/RESULTS-rereview.md
    Four (W/Y)DxR motifs, the DDB1-binding "DxR box" signature of DCAF

References

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Suggested Questions for Experts

Q: Is the D2030.9d (S6FN32) transcript translated from the internal Met74 start in vivo, and if so where does the product localize, given that it lacks both the WDR-23A NES-bearing and the basic WDR-23B N termini?

Q: Does the N-terminally shortened product bind DDB-1 and SKN-1/GEN-1 and promote their turnover like WDR-23B, act like WDR-23A, or neither?

Suggested Experiments

Experiment: Express GFP-tagged D2030.9d cDNA from the endogenous wdr-23 promoter in wdr-23(tm1817) null animals and score localization, gst-4p::gfp repression and brood-size rescue in parallel with WDR-23A-only and WDR-23B-only strains.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · wdr-23-protnlm-predictions-review.yaml · Review status: COMPLETE

The emitted ribosome-binding and translation-regulator terms are not validated by the direct WDR-23 substrate-receptor experiments. The exact product retains its WD-repeat core but has a distinct N-terminal boundary.

Source documents: genes/worm/wdr-23/wdr-23-protnlm-source.json · genes/worm/wdr-23/wdr-23-notes.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0045182 translation regulator activity GO_MF
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-10 · file:worm/wdr-23/wdr-23-protnlm-source.json
Review rationale: The donor is RACK1, whereas direct worm studies establish WDR-23 substrate recruitment and SKN-1/GEN-1 regulation. WD-repeat architecture alone cannot transfer direct translational regulation. Human WDR23 ubiquitylates the histone-mRNA factor SLBP, but that is substrate-adaptor activity on a translation-related protein, not a translation regulator activity, and does not demonstrate this GO activity in S6FN32; an additional role is not experimentally excluded.
Supporting Evidence:
GO:0043022 ribosome binding GO_MF
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-10 · file:worm/wdr-23/wdr-23-protnlm-source.json
Review rationale: The weak sequence match to ribosomal RACK1 does not establish a ribosome-binding interface or ribosome association in this DCAF11/WDR-23 product. Direct WDR-23 studies support a different molecular system, but do not provide a negative ribosome-binding assay.
Supporting Evidence:

Deep Research

Falcon

(wdr-23-deep-research-falcon.md)

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WormBase

(wdr-23-deep-research-wormbase.md)

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📚 Additional Documentation

Notes

(wdr-23-notes.md)

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Bioinformatics Results

(RESULTS.md)

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Protnlm Function Review

(wdr-23-protnlm-function-review.md)

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📄 View Raw YAML

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