## FBXO43
- **UniProt:** Q4G163 (EMI2/ERP1) · **batch:** proteostasis-batch-2026-06-13 · **review status:** COMPLETE
- **PN placement:** `UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|ZBR-type ZnF` ; **PN-node mapping:** F-box subtype/type = no_mapping; group "Cul1 substrate receptor" = mapped, ok_for_propagation_to_go, GO:1990756; class = context_only/too_broad (GO:0061630).
- **Consistency:** **MAJOR PN-vs-review contradiction (the SPECIAL CASE).** Deep research + review correctly establish FBXO43/EMI2 as a non-canonical F-box that does NOT bind SKP1 (PMID:34595750) and is NOT an SCF substrate receptor — it is a direct APC/C INHIBITOR (gonad-restricted meiotic CSF). But the PN node files FBXO43 under "Cul1 substrate receptor" and projects GO:1990756 adaptor activity, which directly conflicts with the review (which MARK_AS_OVER_ANNOTATED on GO:0019005 and GO:0031146, and gives core MF = GO:1990948 ubiquitin ligase inhibitor activity). Review internally consistent and well-evidenced (PMID:34052850 OZEMA12, PMID:34595750 SPGF64, both VERIFIED).
- **PN story / NEW pressure:** Review adds NEW GO:1990948 "ubiquitin ligase inhibitor activity" (OLS-verified real; IMP from PMID:34595750) — the true core MF, absent from GOA. It also correctly REMOVEs the implausible ortholog-transfer IEA GO:1990090 "cellular response to NGF" (the flagged implausible IEA), and MARK_AS_OVER_ANNOTATED the mitotic-division IBA/IEA (paralog over-propagation from EMI1/FBXO5). Conclusion: PN over-reaches by projecting an adaptor MF onto an APC/C inhibitor; the defensible NEW term is GO:1990948, already in the review.
- **Mapping strategy:** **This gene SHOULD change the node treatment.** Per precedent (substrate-receptor MF rejected when the gene is not a receptor), GO:1990756 is wrong for FBXO43 — it is broader/incorrect, not narrower. FBXO43 should be excluded from the GO:1990756 projection / flagged as a non-canonical F-box (APC/C inhibitor), analogous to its paralog FBXO5/EMI1.
- **Evidence alignment:** PN cites only "15340381 / rev" (generic F-box). Review carries the disease/mechanism primaries (PMID:34052850, PMID:34595750) and Falcon EMI2 synthesis — strong divergence; PN's generic citation does not support the substrate-receptor placement.
- **Verdict:** Review correct; PN node mis-files FBXO43 and over-reaches with GO:1990756. **Recommended edits:** [MAP] exclude FBXO43/EMI2 from the GO:1990756 substrate-adaptor projection and flag as non-canonical F-box / APC/C inhibitor (core MF GO:1990948), mirroring FBXO5/EMI1.