## FBXL16
- **UniProt:** Q8N461 · **batch:** proteostasis-batch-2026-06-13 · **review status:** COMPLETE
- **PN placement:** `UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|LRR` ; **PN-node mapping:** group-level `mapped / ok_for_propagation_to_go / GO:1990756`; F-box+LRR subtype/type `no_mapping`; class `context_only / too_broad / GO:0061630`; branch `no_mapping`. NB signature domain is IPR036047 (LRR fold), not the IPR001810 F-box used by siblings.
- **Consistency:** Mostly strong, with one real tension the review handles transparently. PN places FBXL16 as a canonical Cul1 substrate receptor, but falcon + review establish FBXL16 is **non-canonical**: it binds SKP1 but shows **no detectable CUL1 interaction** (Shah 2022), and acts in two opposing modes — degrading some clients (HIF1alpha PMID:34818544; APP) while **stabilizing** others (IRS1, ERalpha, c-MYC, beta-catenin, antagonizing FBXO45). Review verified-cache claim (HIF1alpha) is solid; the stabilizer mode rests on UNVERIFIED falcon DOI leads (flagged as such). Non-canonical caveat is consistently noted across description, GO:0031146 review, and core_functions.
- **PN story / NEW pressure:** PN asserts the generic adaptor MF (GO:1990756, verified real); GOA carries only `protein binding` (IPI, HIF1A). Review uses GO:1990756 in core_functions. The novel pressure is the **stabilizing/anti-degradative mode** with no GO MF — review proposes a new term "protein stabilization by inhibition of ubiquitin-dependent degradation" (candidate, UNVERIFIED — not yet a real GO ID; defensible but needs OLS/GO submission). Conclusion: degradative adaptor MF appropriately added; stabilizer activity is a genuine gap but the proposed term is a candidate, not yet real.
- **Mapping strategy:** Gene PARTLY strains the node. The group adaptor mapping (GO:1990756) is defensible for the degradative HIF1alpha/APP mode, but the "no CUL1 binding" finding means FBXL16 may not be a productive Cul1-SCF — flag as **non-canonical F-box** (per task brief). Adaptor MF is partly inferred (only HIF1alpha is cache-verified). Catalysis correctly excluded from sub-nodes.
- **Evidence alignment:** PN reference only "15340381/rev" (placeholder); review does not cite it. Review uses PMID:34818544 (verified) + 33234069 (family) + falcon leads. Benign divergence; primary stabilizer-mode papers are not PubMed-verified in cache.
- **Verdict:** CONSISTENT-WITH-CAVEATS / ACCEPT degradative mapping. **Flag: non-canonical F-box (no detectable CUL1).** Proposed stabilizer term is candidate/unverified. **Recommended edits:** none to YAML [no change]; [MAP] annotate node that FBXL16 is non-canonical (SKP1+ / CUL1-negative) so GO:1990756 propagation is treated as tentative for this member.