## FBXW4
- **UniProt:** P57775 · **batch:** proteostasis-batch-2026-06-13 · **review status:** COMPLETE
- **PN placement (2 rows):** Row1 `UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|WD40` (PMID:15340381); Row2 `UPS|Ubiquitin and UBL binding|E3 ligase|CUL1 receptor|idiosyncratic Ub binding / WD40` (PMID:21070969). **PN-node mapping:** Row1 group=mapped GO:1990756; Row2 group=mapped GO:0061630 ubiquitin protein ligase activity (new_to_goa); both class nodes context_only/too_broad.
- **Consistency:** Row1 consistent — review treats FBXW4 (dactylin/SHFM3) as an SCF substrate receptor (GO:0019005 IBA/NAS ACCEPT, GO:0031146 ACCEPT, proposed_new_terms GO:1990756) with substrates UNDEFINED; deep research (Lockwood 2013) confirms F-box-dependent SKP1/CUL1/RBX1 + COP9 assembly and MG132-dependent association with ubiquitinated proteins. **Row2 INCONSISTENT/over-reach:** the PN "idiosyncratic Ub binding | E3 ligase" node projects GO:0061630 (catalytic ubiquitin protein **ligase** activity). PMID:21070969 (Pashkova 2010, Mol Cell, [DOI](https://doi.org/10.1016/j.molcel.2010.10.018)) — per PubMed, "WD40 repeat propellers define a ubiquitin-**binding** domain that regulates turnover of F box proteins" — describes the WD40 propeller as a ubiquitin-BINDING module promoting F-box **auto-ubiquitination/turnover**, NOT ligase catalysis. F-box proteins are non-catalytic receptors (catalysis is RBX1 RING). Both the paper's content and the F-box pattern contradict GO:0061630.
- **PN story / NEW pressure:** Row1 ADD GO:1990756 (verified real, new_to_goa) — defensible, already proposed by review. Row2 GO:0061630 over-reaches twice (wrong activity type AND wrong paper interpretation). If anything, PMID:21070969 supports GO:0043130 ubiquitin binding (verified real; molecular function), not ligase activity. Limb-development role (SHFM3, dactylaplasia) is correctly KEEP_AS_NON_CORE / positional, not a molecular function.
- **Mapping strategy:** Row1 correct. **Row2 mapping is wrong:** GO:0061630 should not be projected to F-box receptors from this Ub-binding paper. Recommend the Row2 node project GO:0043130 ubiquitin binding (if at all) or no_mapping — analogous to FBXW7's IBA ubiquitin-binding which the curator marked over-annotated.
- **Evidence alignment:** Row1 PN cites PMID:15340381 (family review). Review uses PMID:10405324/PMID:10471509 (SHFM3/dactylaplasia, HIGH), PMID:10945468, plus falcon (Lockwood 2013). Row2 PN's PMID:21070969 is NOT in the review and its claim (Ub-binding) is mischaracterized by the GO:0061630 mapping.
- **Verdict:** Row1 CONSISTENT (ADD GO:1990756). Row2 PN node OVER-REACHES. **Recommended edits:** [MAP] change Row2 group `Ubiquitin and UBL binding|E3 ligase` projection for FBXW4 from GO:0061630 ubiquitin protein ligase activity to GO:0043130 ubiquitin binding, or set no_mapping — PMID:21070969 documents WD40 ubiquitin BINDING (regulating F-box turnover), not catalytic ligase activity; F-box proteins are non-catalytic.
