FBXW8

UniProt: Q8N3Y1 · batch: proteostasis-batch-2026-06-13 · review status: COMPLETE (high quality)
PN placement (3 rows): Row1 UPS|...|Cul1 substrate receptor|F-box|WD40; Row2 UPS|...|Cul7 substrate receptor|F-box, noncanonical contact|WD40 (PMID:35982156); Row3 UPS|Ubiquitin and UBL binding|E3 ligase|CUL1 receptor|idiosyncratic Ub binding / WD40 (PMID:21070969). PN-node mapping: Row1 group=mapped GO:1990756 (already_in_goa_exact); Row2 group=mapped GO:1990756 (already_in_goa_exact); Row3 group=mapped GO:0061630 (new_to_goa); class nodes context_only/too_broad.
Consistency: Rows 1–2 fully consistent and unusually well grounded. FBXW8 is the exclusive CUL7 F-box partner; review has GO:1990756 (IDA x4, ACCEPT — already in GOA), GO:0031467 Cul7-RING complex (IDA), GO:0019005 SCF KEEP_AS_NON_CORE (reflecting the PMID:35982156 finding that CRL7(FBXW8) is catalytically coupled to CUL1-RBX1), validated substrates IRS1/HPK1/cyclin D1/GORASP1/ATGL. Row2 Cul7 receptor matches GO:0031467; the dossier's own note that CRL7(FBXW8) "lacks intrinsic catalytic activity" reinforces the receptor-not-catalyst pattern. Row3 INCONSISTENT: PN projects GO:0061630 ubiquitin protein ligase activity from PMID:21070969 (Pashkova 2010, DOI) — a ubiquitin-binding WD40 paper about F-box auto-turnover — contradicting both the paper and the structurally-demonstrated non-catalytic nature of FBXW8.
PN story / NEW pressure: Rows 1–2 GO:1990756 already in GOA (IDA) — no new pressure, correctly already_in_goa_exact. Row3 GO:0061630 over-reaches (catalytic term for a structurally non-catalytic receptor; wrong paper interpretation). Both terms verified real via OLS. No defensible NEW catalytic term; the only Ub-binding-derived candidate would be GO:0043130 ubiquitin binding, and FBXW8 has no specific evidence even for that.
Mapping strategy: Rows 1–2 correct (GO:1990756 matches review core MF for both CUL1-coupled and CUL7 contexts; not broader/narrower). Row3 mapping wrong: GO:0061630 should be GO:0043130 ubiquitin binding or no_mapping. The Cul1 vs Cul7 distinction is handled well; the genuine error is the Ub-binding→ligase miscast.
Evidence alignment: Rows 1–2 PN cites PMID:15340381 (family review) and PMID:35982156 (CRL7 structure — also a HIGH-relevance review reference, good overlap). Review adds gene-specific PMID:17205132 (cyclin D1), PMID:18498745 (IRS1), PMID:24362026 (HPK1), PMID:21572988 (GORASP1/Golgi). Row3 PMID:21070969 is NOT in the review and is mischaracterized by GO:0061630.
Verdict: Rows 1–2 CONSISTENT (GO:1990756 already in GOA, both CUL1+CUL7 contexts validated); Row3 PN node OVER-REACHES. Recommended edits: [MAP] change Row3 Ubiquitin and UBL binding|E3 ligase projection for FBXW8 from GO:0061630 ubiquitin protein ligase activity to GO:0043130 ubiquitin binding or no_mapping — PMID:21070969 = WD40 ubiquitin BINDING / F-box auto-turnover, not ligase catalysis; structure (PMID:35982156) shows FBXW8 is non-catalytic.