id: Q09499
gene_symbol: ire-1
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
status: COMPLETE
description: >-
  Focused review of the GO-GPT/BioReason-Pro prediction that ire-1 has
  hydrolase activity acting on ester bonds. The prediction is not a useful new
  annotation: the direct activity is the already curated RNA endonuclease
  activity of the IRE-1 KEN domain, and GO:0016788 is both less informative and
  off the current ontology branch for GO:0004521 RNA endonuclease activity.
references:
- id: doi:10.64898/2026.03.19.712954
  title: 'BioReason-Pro: Advancing Protein Function Prediction with Multimodal Biological Reasoning'
- id: file:worm/ire-1/ire-1-hypotheses/prediction-ester-bond-hydrolase/openscientist.md
  title: OpenScientist focused review of the GO:0016788 ester-bond-hydrolase prediction for worm ire-1
- id: PMID:11780124
  title: IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA.
- id: PMID:11779465
  title: Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development.
- id: file:worm/ire-1/ire-1-gogpt-leaf-predictions.yaml
  title: GO-GPT leaf predictions for worm ire-1
source_documents:
- genes/worm/ire-1/ire-1-gogpt-leaf-predictions.yaml
- genes/worm/ire-1/ire-1-hypotheses/prediction-ester-bond-hydrolase/openscientist.md
- genes/worm/ire-1/ire-1-ai-review.yaml
predictions:
- source_method: GO-GPT
  source_version: bioreason.net/2026-03/rl
  source_reference_id: doi:10.64898/2026.03.19.712954
  predicted_term:
    id: GO:0016788
    label: hydrolase activity, acting on ester bonds
  predicted_term_type: GO_MF
  review:
    assessment: LSP
    confidence_score: 2
    summary: >-
      IRE-1 cleaves phosphodiester bonds in xbp-1 mRNA, so the prediction is
      chemically adjacent to the true activity but less precise than the
      accepted GO:0004521 RNA endonuclease activity already present on the
      review. In the current GO structure, GO:0016788 is not an asserted
      ancestor of RNA endonuclease activity, while IRE-1 already carries the
      more precise RNA nuclease and RNA endonuclease terms. LSP is preferred
      over NPI or UNC because the broad ester-hydrolase chemistry is adjacent
      to the curated nuclease activity, but the proposed term is off-branch
      and redundant.
    supported_by:
    - reference_id: PMID:11780124
      supporting_text: Purified mouse IRE1 accurately cleaved XBP-1 mRNA in vitro, indicating that XBP-1 mRNA is a direct target of IRE1 endonucleolytic activity
    - reference_id: PMID:11779465
      supporting_text: C. elegans requires ire-1-mediated splicing of xbp-1 mRNA for UPR gene transcription and survival upon ER stress
    - reference_id: file:worm/ire-1/ire-1-hypotheses/prediction-ester-bond-hydrolase/openscientist.md
      supporting_text: GO:0016788 adds no information beyond these.
    - reference_id: file:worm/ire-1/ire-1-hypotheses/prediction-ester-bond-hydrolase/openscientist.md
      supporting_text: GO:0016788 is NOT an ancestor of GO:0004521