## FBXO5

- **UniProt:** Q9UKT4 (FBXO5/EMI1) · **batch:** proteostasis-batch-2026-06-13 (Falcon DR) · **review status:** COMPLETE
- **PN placement:** `UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|ZBR-type ZnF` ; **PN-node mapping:** group `Cul1 substrate receptor`=`mapped`/ok_for_propagation→GO:1990756; F-box/ZBR subtype+type=`no_mapping`; class=`context_only`/too_broad→GO:0061630.
- **Consistency:** CONTRADICTION (substantive, by design). The PN places EMI1 in the SCF substrate-receptor group and projects GO:1990756 adaptor activity. The review (correctly per the SPECIAL CASE) treats EMI1 as a **non-canonical F-box whose dominant function is APC/C INHIBITION, not productive SCF substrate reception**: core MF = GO:1990948 ubiquitin ligase inhibitor activity (verified real; ACCEPT, IDA PMID:15148369). Review explicitly demotes the ComplexPortal SCF-receptor NAS to non-core and MARK_AS_OVER_ANNOTATED for SCF-dependent catabolism / protein ubiquitination (EMI1 is a SCF^BTRC *substrate*, not a productive receptor). Falcon DR ↔ review agree; both diverge from the PN node framing.
- **PN story / NEW pressure:** The PN role (generic SCF receptor → GO:1990756) is NOT supported as core for this gene and is contradicted by the well-documented inhibitor biology. No new term needed: the accurate MFs (GO:1990948 inhibitor activity; GO:0010997 anaphase-promoting complex binding; GO:1904667/GO:0051444 negative regulation of ligase/transferase) are already in GOA and accepted. A single 2024 report frames SCF^EMI1/RAD51, but the review rightly does not let it overturn the inhibitor role. Conclude: PN adaptor projection over-reaches for FBXO5.
- **Mapping strategy:** This gene SHOULD change/qualify the node. Like FBXO2/FBXO6 (lectin) but more strongly, EMI1 is an exception to the Cul1-substrate-receptor → GO:1990756 default. Recommend marking FBXO5/EMI1 (and ZBR-type-ZnF F-box) so the GO:1990756 projection is suppressed or flagged "non-canonical / APC-C inhibitor" rather than propagated as a productive adaptor.
- **Evidence alignment:** PN reference only "15340381 / rev". Review uses gene-specific primary literature: PMID:15148369 (inhibitor activity, IDA), 23708605 (DisProt IDR inhibition), 15148369/15469984-class APC/C-binding, 17875940 (genome-stability IMP), plus Falcon DR. No overlap with PN; review evidence is far richer and on-point.
- **Verdict:** PN node placement is misleading for EMI1 — adaptor projection (GO:1990756) should NOT propagate; review correctly anchors on GO:1990948 inhibitor activity (in GOA). Over-reach on the PN side.
- **Recommended edits:** none to FBXO5-ai-review.yaml (review is correct). [MAP] Flag FBXO5/EMI1 as a non-canonical F-box (APC/C inhibitor) so GO:1990756 is NOT propagated to it; its core MF is GO:1990948 ubiquitin ligase inhibitor activity.