## FBXO40
- **UniProt:** Q9UH90 · **batch:** proteostasis-batch-2026-06-13 · **review status:** COMPLETE
- **PN placement:** `UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|TRAF-type ZnF` ; **PN-node mapping:** F-box subtype/type = no_mapping; group = mapped, ok_for_propagation_to_go, GO:1990756; class = context_only/too_broad (GO:0061630).
- **Consistency:** Consistent and the best-characterized of the set. Deep research (Falcon, anchored on Shi et al. 2011 PMID:22033112), review YAML, and PN mapping agree: muscle-restricted SCF substrate receptor whose validated substrate is IRS1, limiting IGF-1/insulin->IRS1->PI3K/AKT signaling. Review applies the KEY F-box PATTERN cleanly: MODIFY of the IEA catalytic GO:0061630 (ubiquitin protein ligase activity) -> GO:1990756 adaptor activity. No internal contradictions.
- **PN story / NEW pressure:** PN asserts only the generic adaptor role, but FBXO40 has a real substrate-specific BP NOT in GOA. Review adds NEW GO:0046627 "negative regulation of insulin receptor signaling pathway" (OLS-verified real). Defensible: SCF-FBXO40 ubiquitinates IRS1, Fbxo40 loss stabilizes IRS1 and causes IRS1-dependent muscle hypertrophy. Honestly recorded as ISO (mouse ortholog; PMID:22033112 NOT in cache — confirmed). Conclusion: **ADD** GO:0046627 (already in the review). MF/CC otherwise captured.
- **Mapping strategy:** Gene does not change the node. GO:1990756 matches; node-level scope correct. The FBXO40-specific GO:0046627 lives in the review as a NEW substrate-specific term, appropriately not propagated to the shared PN node (too specific for the group). Catalytic-ligase IEA correctly demoted per pattern.
- **Evidence alignment:** PN cites only "15340381 / rev." Review uses PMID:17928169 (muscle-specific expression, VERIFIED), PMID:22033112 (IRS1, UNVERIFIED/ISO), PMID:34445249 (NAS), Falcon, Reactome. Substantial divergence: review carries the substrate-level primary literature PN lacks.
- **Verdict:** Consistent; correct F-box MODIFY pattern; defensible verified NEW BP (GO:0046627). ACCEPT review. **Recommended edits:** none required; optionally [REF] upgrade PMID:22033112 to VERIFIED if full text read.