The C. elegans proteostasis network

Reviewing GO annotations for chaperones, degradation machinery and longevity regulators

AI Gene Review · projects/CAEEL_PROTEOSTASIS · 2026

Bottom line

  • The network folds, holds and clears proteins; in worms its capacity declines with age under insulin/FOXO control.
  • We reviewed every GO annotation on 17 genes: 773 rows, 597 ACCEPT, 56 MODIFY, 4 REMOVE, 10 NEW.
  • Most changes replace protein binding with more specific terms. The worm has one HSP90, HSP-90 (Q18688); daf-21 is its old mutant name, and PR #3225 retires the duplicate review under that name.

Why proteostasis in the worm

  • Short lifespan and a transparent body: aggregation can be watched in live animals.
  • Worm models of polyQ, amyloid-beta, alpha-synuclein and SOD1 aggregation.
  • HSF-1 activity drops at reproductive maturity; DAF-16 (FOXO) extends capacity.
  • Test: do chaperone annotations keep mechanism (foldase vs holdase) and not just "binds unfolded protein"?

The network and the 17 genes

Actions per gene

Holdase is not foldase

hsp-16.2 review page. The small HSP holds substrates without ATP, so protein refolding (IBA) is removed. The obsolete unfolded protein binding is kept until GO has a holdase term.

Findings

  1. protein binding → specific binding terms: HSP-1 partners → protein-folding chaperone binding. ⚠️ The 9 hsp-90 IPI rows propose Hsp90 protein binding (GO:0051879), which means binding to Hsp90 and belongs on partners (STI-1, UNC-45); to be corrected.
  2. Holdase vs foldase: HSP-16.2 protein refolding removed.
  3. Artefacts removed: LGG-1 GABA receptor binding (IBA), AAK-2 positive regulation of protein secretion, SKN-1 regulation of translation.
  4. One HSP90, not two: daf-21 is a synonym of hsp-90 (Q18688), not a paralog; the accession P41887 once given for it is fission-yeast Swo1.

Status and next steps

  • ✅ 17 gene reviews and the pathway summary complete.
  • ⬜ Duplicate daf-21 review retired in PR #3225 (approved, pending merge); hsp-90 is the single HSP90 review.
  • ⬜ Re-target the 9 hsp-90 GO:0051879 MODIFY rows (GO:0051087 for co-chaperones; chaperone activity for clients).
  • ⬜ The status section on the project page (868 rows, 626 ACCEPT) predates later edits.
  • ⬜ Only cct-1, cct-8 and rpn-10 of the chaperonin and proteasome subunits on the page have reviews; the rest are not yet reviewed.

Read more: projects/CAEEL_PROTEOSTASIS.md · projects/CAEEL_PROTEOSTASIS/ · genes/worm/<gene>/