## TXNDC11
- **UniProt:** Q6PKC3 (EFP1) · **batch:** proteostasis-batch-2026-06-11 · **review status:** COMPLETE
- **PN placement:** `ER proteostasis | Folding enzyme | Protein disulfide isomerases` ; **PN-node mapping:** group=mapped, scope=ok_for_propagation_to_go, GO=GO:0003756 protein disulfide isomerase activity (class/branch=no_mapping). Projection goa_status=new_to_goa.
- **Consistency:** Partial mismatch on the catalytic activity. Review, notes, and deep research converge that TXNDC11 is a **disulfide reductase**, not an isomerase/oxidase: only Trx5 carries a bona fide CXXC (CGFC, C692/C695), the other four Trx folds are degenerate, and Trx5 has reduction-potential (~−234 mV) behaving "as a reductase rather than an oxidase" (PMID:32065582; Timms 2016). The review's core MF and proposed_new_terms use GO:0015035 protein-disulfide reductase activity. The PN node projects GO:0003756 (isomerase). Verified via OLS: GO:0003756 (isomerase, S-S rearrangement) and GO:0015035 (reductase) are **siblings under different parents**, not parent/child — so GO:0003756 does not subsume the reductase function and is an over-projection for this specific member.
- **PN story / NEW pressure:** Strong NEW pressure — TXNDC11 GOA has NO molecular-function term at all (only protein binding + localizations; verified goa.tsv). A catalytic MF should be added, but as GO:0015035 protein-disulfide reductase activity (verified real), not GO:0003756. The review also proposes a BP gap: glycoprotein ERAD (GO:0036503 ERAD pathway / GO:0097466 ubiquitin-dependent glycoprotein ERAD pathway, both verified real) via the disulfide-linked EDEM2 mannose-trimming complex. Conclusion: ADD GO:0015035 (MF) + GO:0097466/GO:0036503 (BP).
- **Mapping strategy:** The "Protein disulfide isomerases" group's GO:0003756 projection over-reaches for TXNDC11 specifically (it lacks canonical PDI isomerase activity). Group-level GO:0003756 may be right for canonical members but is the wrong activity class for this non-canonical reductase. The node mapping itself need not change, but TXNDC11 should be flagged as a group member whose projected isomerase term should NOT be propagated (scope exception), or projected as reductase.
- **Evidence alignment:** PN mapping-only. Review key refs: PMID:32065582 (EDEM2-TXNDC11 reductase, gpERAD), PMID:30374462, PMID:15561711 (legacy DUOX/EFP1). The reductase-not-isomerase evidence directly undercuts the PN isomerase projection.
- **Verdict:** Inconsistent on activity class — PN GO:0003756 (isomerase) over-projects; review-supported activity is GO:0015035 reductase. MF is genuinely missing from GOA.
- **Recommended edits:** [MAP] Flag TXNDC11 in the "Protein disulfide isomerases" group as a non-canonical reductase: do not propagate GO:0003756 to it; project GO:0015035 protein-disulfide reductase activity instead. [YAML] Optionally tighten the TXNDC11 proposed_new_terms to GO:0097466 (ubiquitin-dependent glycoprotein ERAD pathway) as the precise BP, and drop the GO:0003756 alternative wording in favor of GO:0015035.