## AGR2
- **UniProt:** O95994 · **batch:** proteostasis-batch-2026-06-03 · **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 `ER proteostasis`=no_mapping.
- **Consistency:** Deep research (Falcon), notes, review YAML, and the PN PDI mapping are consistent. All frame AGR2 as a secretory/ER-retained (KTEL) **PDI-family/thioredoxin-fold foldase** that forms mixed disulfides with MUC2 and is required for gel-forming mucin production (PMID:19359471, 34237462). The review honestly tracks the literature conflict (PMID:25666625 argued EGFR, not MUC2, is the major mixed-disulfide substrate) but defensibly weights the MUC2/mucin model as core. No internal contradiction.
- **PN story / NEW pressure:** GO:0003756 (OLS-verified real) is **not** in AGR2's GOA (GOA MF = dystroglycan/EGFR/identical-protein/homodimerization binding only), confirming PN's new_to_goa. The review **adds** it as a MODIFY proposed_replacement for two generic protein-binding rows (PMID:19359471, 34237462), alongside GO:0034975 protein folding in ER. This matches the PN projection. Caveat: AGR2 is a non-canonical "pseudo-PDI" (CXXS, single active-site Cys), so true isomerase catalysis is debated; the review's mixed-disulfide/foldase framing is the safest support. Conclusion: legitimate ADD, executed; mild over-reach risk on the term name only.
- **Mapping strategy:** Group-level GO:0003756 is the cleanest catalytic-family target and is correctly scoped (review does not extend to broad ER proteostasis or generic UPR). The review separately adds a narrow IRE1beta-repression UPR role (PMID:38177498/38177501) the PN node does not surface — enrichment, not conflict. No mapping change needed.
- **Evidence alignment:** PN dossier lists no reference titles for AGR2. Review evidence (PMID:19359471, 22184114, 23274113, 25666625, 31040128, 34237462, 38177498/501) is reviewer-supplied; alignment is by biology (PDI/mucin), not shared citation list.
- **Verdict:** Consistent; PN GO:0003756 projection validated and added via MODIFY; only nuance is the pseudo-PDI catalysis debate (review mitigates via mixed-disulfide evidence). **Recommended edits:** none required; [REF] optionally note in review that AGR2 is a non-canonical CXXS PDI-family member (catalytic isomerase activity debated) to pre-empt over-reading GO:0003756.