## AIRE
- **UniProt:** O43918 · **batch:** proteostasis-batch-2026-06-03 · **review status:** COMPLETE
- **PN placement:** `Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING variant|PHD|other` ; **PN-node mapping:** PHD/RING-variant subtype+type no_mapping; *group* (RING variant) mapped→GO:0061630 (ubiquitin protein ligase activity, propagate); class context_only (too_broad). Projection: **GO:0061630 new_to_goa**.
- **Consistency:** Major contradiction between PN annotation and review. PN classifies AIRE as a catalytic E3 ligase (RING-variant/PHD) and projects GO:0061630 as a new GOA annotation. The review and notes treat AIRE strictly as a nuclear chromatin reader / Pol II transcriptional activator (PHD1 = H3K4me0 histone reader, PMID:18292755, 19446523) and **explicitly decline** to add GO:0061630, adding instead a suggested experiment to test for absent E3 activity. Deep research (manual) and review are internally consistent; the PN node is the outlier.
- **PN story / NEW pressure:** PN asserts an E3-ligase MF not in GOA. GO:0061630 is a real term, but for AIRE this is a **domain-bucket inference** (PHD≈RING fold) not supported by the cached AIRE evidence, which characterizes the PHD as a histone-recognition module, not a catalytic ligase. Verdict: over-reaches as currently projected; treat as candidate requiring direct ubiquitin-transfer evidence, not an automatic ADD. (Some non-cached mouse literature reports AIRE E2-binding/E3-like activity — flag for full-text check before any REMOVE/ADD verdict; reviewer's conservative non-adoption is defensible.)
- **Mapping strategy:** The RING-variant group→GO:0061630 propagation is biologically safe for canonical RING E3s but **mis-fires on the PHD/"other" subtype** that AIRE occupies. The subtype is already no_mapping; the issue is the parent group propagating catalytic activity down to a histone-reader PHD. Mapping should not project GO:0061630 onto PHD-only members lacking ligase evidence.
- **Evidence alignment:** Divergent. PN cites PMIDs 14734522 and 15150263 (not in the review's reference list); review is built on the chromatin/transcription corpus (PMID:11533054, 18292755, 19446523, 26084028). No PMID overlap — the PN E3 case rests on references the review never adjudicated.
- **Verdict:** PN E3-ligase placement/projection over-reaches for AIRE; review correctly withholds GO:0061630 pending direct evidence.
- **Recommended edits:** [MAP] Mark AIRE (and other PHD-"other" members) as a gene-level exception to the RING-variant→GO:0061630 propagation, or downgrade that subtree to context_only, since PHD-reader members are not demonstrated catalytic E3s. [REF] Adjudicate PMID:14734522 and PMID:15150263 (the PN E3 references) — fetch full text and record a reference_review before any E3 verdict.