ERP27 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q96DN0
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-07b
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: ERP27 (endoplasmic reticulum resident protein 27; ER protein 27; also known as C12orf46) is a soluble, ER-lumenal, two-domain member of the protein disulfide isomerase (PDI) family that is catalytically inactive. Unlike redox-active PDIs, it lacks the CXXC thioredoxin active-site motif and therefore cannot itself catalyze thiol-disulfide exchange; its thioredoxin-like domains correspond to the non-catalytic b and b' substrate-binding domains of PDI. ERP27 binds unfolded/misfolded proteins through a hydrophobic substrate-binding cleft in its C-terminal (b'-like) domain, discriminating folded from unfolded clients, and presents/recruits the catalytic PDI-family oxidoreductase PDIA3 (ERp57) to those substrates via a defined PDIA3-binding surface (residues 230-233). It is retained in the ER lumen by a C-terminal retention motif, is induced during ER stress / the unfolded protein response, and is enriched in the pancreas. Functionally it acts as a non-catalytic chaperone/substrate-recruiter within the ER oxidative-folding machinery rather than as a disulfide isomerase.
- Existing/core annotation action counts: ACCEPT: 3; KEEP_AS_NON_CORE: 7
PN Consistency Summary
- Consistency: Direct contradiction. Notes and review YAML both establish that ERP27 is a catalytically inactive, non-catalytic PDI-family member that LACKS the CXXC active-site motif and therefore cannot perform thiol-disulfide exchange. The review contains an explicit negated annotation —
GO:0003756 protein disulfide isomerase activity, negated: true (IBA, GO_REF:0000033), action ACCEPT — i.e. the curated record states ERP27 does NOT have PDI activity. The PN group node projects the exact same term GO:0003756 as new_to_goa (a positive addition). PN proposes adding the precise term the review explicitly negates. This is the hardest conflict in the batch.
- PN story / NEW pressure: GO:0003756 (OLS-verified) must NOT be added to ERP27 — it is biologically wrong (no CXXC) and is already correctly captured as a NOT annotation in GOA/review. ERP27's real core functions are GO:0051082 unfolded protein binding (substrate discrimination via the b'-like cleft, PMID:23192347) and GO:0051087 protein-folding chaperone binding (recruits/presents substrates to the catalytic PDIA3/ERp57, PMID:16940051/23192347) — both added in the review, neither surfaced by the PN node. Conclusion: PN projection over-reaches / is incorrect; the review's substrate-presenter framing is the right model.
- Evidence alignment: PN dossier lists no reference titles. Review evidence (PMID:16940051 founding non-catalytic characterization, GOA-anchored to GO:0005788 EXP; PMID:23192347 crystal structure + ITC substrate discrimination) is reviewer-supplied and directly supports the non-catalytic substrate-presenter role. No shared citation list to compare; the biology flatly opposes the PN GO:0003756 projection.
- Verdict: Contradiction — PN projects GO:0003756 (new_to_goa) onto a gene whose review explicitly NEGATES that exact term (no CXXC, catalytically inactive). PN over-reaches; review is correct. Recommended edits: [MAP] remove/suppress the GO:0003756 projection for ERP27 (it is a non-catalytic PDI-family member; the term is correctly a NOT annotation). If a positive mapping is wanted, target GO:0051082 unfolded protein binding and/or GO:0051087 protein-folding chaperone binding (both OLS-real, both already in the review's core_functions).
Full Consistency Review
- UniProt: Q96DN0 · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
- PN placement:
ER proteostasis|Folding enzyme|Protein disulfide isomerases. PN-node mapping: group Protein disulfide isomerases=mapped→GO:0003756 protein disulfide isomerase activity (new_to_goa); class Folding enzyme=no_mapping; branch=no_mapping.
- Consistency: Direct contradiction. Notes and review YAML both establish that ERP27 is a catalytically inactive, non-catalytic PDI-family member that LACKS the CXXC active-site motif and therefore cannot perform thiol-disulfide exchange. The review contains an explicit negated annotation —
GO:0003756 protein disulfide isomerase activity, negated: true (IBA, GO_REF:0000033), action ACCEPT — i.e. the curated record states ERP27 does NOT have PDI activity. The PN group node projects the exact same term GO:0003756 as new_to_goa (a positive addition). PN proposes adding the precise term the review explicitly negates. This is the hardest conflict in the batch.
- PN story / NEW pressure: GO:0003756 (OLS-verified) must NOT be added to ERP27 — it is biologically wrong (no CXXC) and is already correctly captured as a NOT annotation in GOA/review. ERP27's real core functions are GO:0051082 unfolded protein binding (substrate discrimination via the b'-like cleft, PMID:23192347) and GO:0051087 protein-folding chaperone binding (recruits/presents substrates to the catalytic PDIA3/ERp57, PMID:16940051/23192347) — both added in the review, neither surfaced by the PN node. Conclusion: PN projection over-reaches / is incorrect; the review's substrate-presenter framing is the right model.
- Mapping strategy: This gene exposes the core flaw of the
Protein disulfide isomerases group projecting GO:0003756 to all leaves: the node lumps catalytic isomerases (P4HB, AGR2-debated), redox oxidases (ERO1A/B), and non-catalytic members (ERP27). For ERP27 the projection is not merely broad (TOMM20/HSPA8/RAB7A precedent) but actively wrong, contradicting an explicit negation. Gene-level mapping for ERP27 should be no_mapping for GO:0003756 (or carry the negation), with any positive mapping pointing at unfolded protein binding / chaperone-binding.
- Evidence alignment: PN dossier lists no reference titles. Review evidence (PMID:16940051 founding non-catalytic characterization, GOA-anchored to GO:0005788 EXP; PMID:23192347 crystal structure + ITC substrate discrimination) is reviewer-supplied and directly supports the non-catalytic substrate-presenter role. No shared citation list to compare; the biology flatly opposes the PN GO:0003756 projection.
- Verdict: Contradiction — PN projects GO:0003756 (new_to_goa) onto a gene whose review explicitly NEGATES that exact term (no CXXC, catalytically inactive). PN over-reaches; review is correct. Recommended edits: [MAP] remove/suppress the GO:0003756 projection for ERP27 (it is a non-catalytic PDI-family member; the term is correctly a NOT annotation). If a positive mapping is wanted, target GO:0051082 unfolded protein binding and/or GO:0051087 protein-folding chaperone binding (both OLS-real, both already in the review's core_functions).
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07b
- review_yaml: genes/human/ERP27/ERP27-ai-review.yaml
- PN workbook rows: 1
PN row 1: ER proteostasis | Folding enzyme | Protein disulfide isomerases
- UniProt: Q96DN0
- In branches: ER
- PN-node mapping records (path + ancestors):
- [group] ER proteostasis|Folding enzyme|Protein disulfide isomerases
status=mapped scope=ok_for_propagation_to_go GO=[GO:0003756 protein disulfide isomerase activity]
rationale: This PN group captures the canonical ER protein-disulfide-isomerase folding enzymes. GO protein disulfide isomerase activity is the cleanest propagation target for the catalytically active family members.
- [class] ER proteostasis|Folding enzyme
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [branch] ER proteostasis
status=no_mapping scope= GO=[]
rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.
Projected GO annotations (1)
- GO:0003756 protein disulfide isomerase activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Folding enzyme|Protein disulfide isomerases
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.