FBXW9 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q5XUX1
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-13
- Batch change status: added
Source Files Checked
Deep Research Files
AIGR Review Snapshot
- Description: FBXW9 is a member of the F-box/WD40 (FBXW) family of proteins, containing an N-terminal F-box motif and a C-terminal beta-propeller built from seven WD40 repeats. F-box proteins serve as the interchangeable substrate-recognition subunits of SCF (SKP1-CUL1-F-box)-type cullin-RING E3 ubiquitin ligase complexes: the F-box motif binds SKP1 (which in turn bridges to CUL1 and the RBX1-bound catalytic RING), while the WD40 propeller engages substrate proteins and presents them for ubiquitination, marking them for proteasomal degradation. FBXW9 is itself non-catalytic: it acts as a substrate adaptor, with the ubiquitin-transfer (RING) activity contributed by RBX1 in the assembled SCF. FBXW9 has been shown experimentally to bind SKP1 (array MAPPIT screen with co-immunoprecipitation validation) and to co-purify with CUL1 in affinity purification-mass spectrometry of SCF assemblies, and ComplexPortal assigns it as the variable substrate-receptor subunit of an SCF complex variant. It is broadly expressed and undergoes N-terminal phosphorylation at several residues. FBXW9 remains poorly characterized at the level of direct biochemistry: no endogenous ubiquitination substrate has been validated by direct ubiquitination or degradation assays. Cancer-focused studies place FBXW9 transcription downstream of p53 (a direct p53 target gene) and of CREB in an IGFBP5-ROR1/HER2 signaling axis, and report cell-cycle/proliferation phenotypes on knockdown in breast cancer and invasion phenotypes in glioblastoma stem-like cells; however, candidate substrates such as TP53 remain predicted rather than biochemically demonstrated, so FBXW9's assigned molecular and process roles still rest largely on family-level inference.
- Existing/core annotation action counts: ACCEPT: 1; KEEP_AS_NON_CORE: 15
PN Consistency Summary
- Consistency: Consistent. Deep research (falcon), review YAML, PN annotation, and node mapping all treat FBXW9 as an SCF/CRL1 substrate adaptor whose specific substrate(s) are NOT experimentally defined (TP53 is UbiBrowser-predicted only). The review is appropriately cautious: SCF membership ACCEPT, but GO:0031146 catabolic process is KEEP_AS_NON_CORE because no substrate is biochemically validated. No contradictions.
- PN story / NEW pressure: PN asserts the generic Cul1-receptor adaptor role. GOA currently lacks GO:1990756, so the projected term is correctly
new_to_goa; the review proposes it under proposed_new_terms (GO:1990756, verified real via OLS). This is the flagged "member with NO validated substrate" case — adaptor activity is defensible from SKP1 binding (co-IP) + CUL1 AP-MS even without a known substrate. Conclusion: ADD GO:1990756 (already proposed by review); do not add any process/substrate term.
- Evidence alignment: PN cites PMID:15340381 ("/ rev", SCF family review). Review anchors on PMID:15520277 (F-box nomenclature), PMID:19159283 (array MAPPIT SKP1 + co-IP), and falcon (CUL1 AP-MS). Different family-review citations but same adaptor conclusion; no conflict.
- Verdict: CONSISTENT — no edits. Poorly-characterized but bona fide F-box receptor (no validated substrate); GO:1990756 ADD already proposed.
Full Consistency Review
- UniProt: Q5XUX1 · batch: proteostasis-batch-2026-06-13 · review status: COMPLETE
- PN placement:
UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|WD40 ; PN-node mapping: group=mapped/ok_for_propagation_to_go GO:1990756; class=context_only/too_broad GO:0061630; subtype/type/branch=no_mapping
- Consistency: Consistent. Deep research (falcon), review YAML, PN annotation, and node mapping all treat FBXW9 as an SCF/CRL1 substrate adaptor whose specific substrate(s) are NOT experimentally defined (TP53 is UbiBrowser-predicted only). The review is appropriately cautious: SCF membership ACCEPT, but GO:0031146 catabolic process is KEEP_AS_NON_CORE because no substrate is biochemically validated. No contradictions.
- PN story / NEW pressure: PN asserts the generic Cul1-receptor adaptor role. GOA currently lacks GO:1990756, so the projected term is correctly
new_to_goa; the review proposes it under proposed_new_terms (GO:1990756, verified real via OLS). This is the flagged "member with NO validated substrate" case — adaptor activity is defensible from SKP1 binding (co-IP) + CUL1 AP-MS even without a known substrate. Conclusion: ADD GO:1990756 (already proposed by review); do not add any process/substrate term.
- Mapping strategy: Correct and conservative. Group-level GO:1990756 matches the review's proposed MF; not broader/narrower. Class-level GO:0061630 correctly too_broad. No node change.
- Evidence alignment: PN cites PMID:15340381 ("/ rev", SCF family review). Review anchors on PMID:15520277 (F-box nomenclature), PMID:19159283 (array MAPPIT SKP1 + co-IP), and falcon (CUL1 AP-MS). Different family-review citations but same adaptor conclusion; no conflict.
- Verdict: CONSISTENT — no edits. Poorly-characterized but bona fide F-box receptor (no validated substrate); GO:1990756 ADD already proposed.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-13
- review_yaml: genes/human/FBXW9/FBXW9-ai-review.yaml
- PN workbook rows: 1
PN row 1: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul1 substrate receptor | F-box | WD40
- UniProt: Q5XUX1
- In branches: UPS
- Signature domains: IPR001810
- Auxiliary domains: IPR001680
- PN references (titles):
- PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|WD40
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
- [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
- [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor
status=mapped scope=ok_for_propagation_to_go GO=[GO:1990756 ubiquitin-like ligase-substrate adaptor activity]
rationale: This PN group captures substrate receptors/adaptors for cullin/UBL ligase systems. The shared GO molecular-function target is ubiquitin-like ligase-substrate adaptor activity.
- [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
- [branch] Ubiquitin Proteasome System
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.
Projected GO annotations (1)
- GO:1990756 ubiquitin-like ligase-substrate adaptor activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.