## AHR
- **UniProt:** P35869 · **batch:** proteostasis-batch-2026-06-03 · **review status:** COMPLETE
- **PN placement:** `Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul4A/Cul4B substrate adaptor|AHR / ARNT / TBL3 complex|PAS` ; **PN-node mapping:** subtype(PAS)/type(AHR/ARNT/TBL3) `no_mapping`; group (Cul4A/Cul4B substrate adaptor) `mapped` GO:1990756 ubiquitin-like ligase-substrate adaptor activity (new_to_goa); class (E3 ligases) `context_only` too_broad GO:0061630; branch `no_mapping`. PN references: PMID:17392787, 28416634 (titles not in dossier; not cached locally).
- **Consistency:** Large but well-managed divergence. PN frames AHR as a CUL4 substrate adaptor in the UPS branch. Deep research (falcon) and review establish AHR's canonical identity as a ligand-activated bHLH-PAS nuclear receptor / RNA Pol II transcription factor (HSP90/XAP2/p23 cytosolic complex → ARNT heterodimer → XRE binding). The review/notes explicitly did NOT accept the PN GO:1990756 projection: AHR's own subtype/type are `no_mapping`, and the parent group is flagged `manual_gene_level_review_required_before_gene_review_change`. Notes acknowledge CUL4B^AHR E3 activity from the literature (Xie 2024 review; ER-α/AR/β-catenin targets) but retain it as an open question, not an annotation. Internally consistent; PN UPS role deliberately not propagated.
- **PN story / NEW pressure:** PN asserts an MF (GO:1990756, verified real/non-obsolete) absent from GOA. AHR-as-CUL4-adaptor is supported only by a subset of (largely review/secondary) literature and is mechanistically contested vs. AHR being itself a CUL4 substrate. Verdict: **over-reaches** as a gene-level GO assertion now — correctly deferred (suggested_question + suggested_experiment to test direct substrate-bridging vs AHR turnover). The genuine AHR core functions (nuclear receptor activity, heterodimerization, sequence-specific DNA binding, Hsp90 binding) are already richly annotated.
- **Mapping strategy:** Gene does not change the node. The Cul4A/Cul4B substrate-adaptor group→GO:1990756 mapping is too liberal for AHR; AHR's leaf nodes are appropriately `no_mapping`, and the review upholds that. This is a stronger "do not propagate" case than broader-term rejections (TOMM20/HSPA8/RAB7A) because the asserted MF is a different biological role from AHR's primary function.
- **Evidence alignment:** No overlap between PN refs (PMID:17392787, 28416634 — uncached, not used) and the review's evidence base (PMID:34521881, 28602820, 7961644, 11259606, 15641800, 32818467, etc.). The review builds the canonical TF case independently; the PN UPS citations are neither verified nor relied upon. Divergent reference sets, reconciled by treating the UPS role as unverified.
- **Verdict:** PN UPS/CUL4-adaptor projection (GO:1990756) over-reaches; correctly NOT propagated to AHR (left as open question). Core TF/nuclear-receptor function fully captured. **Recommended edits:** none to YAML. [MAP]: keep AHR/ARNT/TBL3 and PAS subtypes `no_mapping`; gate the Cul4A/Cul4B substrate-adaptor group GO:1990756 behind per-gene review (AHR is the cautionary case). [REF]: optionally fetch/verify PN PMID:17392787 & 28416634 to substantiate or retire the AHR UPS placement.