## RNF166
- **UniProt:** Q96A37 · **batch:** proteostasis-batch-2026-06-14 · **review status:** COMPLETE (thorough; catalytic C3HC4 RING E3; p62 K29/K33 xenophagy + TRAF3/6 K63 antiviral; 3 PN rows)
- **PN placement:** row1 `ALP|...|Marking substrates for selective autophagy|Xenophagy|Catalyzes K33-linked ubiquitination of p62`; row2 `UPS|E3 ligases|RING|TRAC-1`; row3 `UPS|Ubiquitin and UBL binding|E3 ligase|RING / TRAC-1|UIM`. **PN-node mapping:** row1 Xenophagy type→mapped GO:0098792 xenophagy; rows2/3 E3-group→mapped GO:0061630 ubiquitin protein ligase activity (classes context_only/too_broad; subtypes no_mapping).
- **Consistency:** Excellent. Deep research, review and PN all agree RNF166 is a genuine catalytic RING E3 (ligase-dead C33A/C36A abolishes activity) that drives xenophagy of cytosolic bacteria by K29/K33-ubiquitinating p62 and recruiting p62/NDP52 (PMID:27880896), and potentiates antiviral type-I-IFN via K63-Ub of TRAF3/TRAF6 (PMID:26456228). PN row1 leaf ("Catalyzes K33-linked ubiquitination of p62") matches the review exactly. Row3's UIM note matches the UniProt C-terminal UIM. No contradictions.
- **PN story / NEW pressure:** Row1 projects GO:0098792 xenophagy (verified real; ABSENT from GOA). This is a strongly defensible **ADD** — and the review itself proposes GO:0098792 as a NEW term (plus GO:0042742 defense response to bacterium and GO:0032481 positive regulation of type I IFN production), fully concordant with the dossier goa_status=new_to_goa. Rows2/3 GO:0061630 = already_in_goa_exact (IBA/EXP/IEA present) — keep catalytic ligase MF as core (matches KEY PATTERN). So PN and review agree: ADD xenophagy; ligase MF already captured.
- **Mapping strategy:** Correct. Catalytic RING→GO:0061630 (exact, in GOA); Xenophagy type→GO:0098792 (narrower-but-inside). Subtype p62-K33 leaf and the TRAC-1/UIM architecture subdivisions appropriately no_mapping. The two separate RING/E3 rows both projecting GO:0061630 are redundant but harmless (one MF). No over-reach.
- **Evidence alignment:** Strong. PN row1 cites "RNF166 Determines Recruitment of Adaptor Proteins during Antibacterial Autophagy" (= PMID:27880896, the review's HIGH/VERIFIED anchor) plus a p62-UBA-Ub review (tandfonline). Row3 cites PMID:17990982 (not in the review). Review additionally anchors the antiviral arm on PMID:26456228 (not in PN). Minor divergence on antiviral evidence only.
- **Verdict:** Fully consistent; xenophagy ADD is justified and the review ALREADY proposes it; catalytic ligase MF already core/in-GOA.
- **Recommended edits:** [YAML] none required for the PN story — the review already proposes GO:0098792 xenophagy (NEW). Optionally [REF] check PN row3's PMID:17990982 (UIM characterization), absent from the review, if a UIM ubiquitin-reader MF is desired.