# PN dossier: FBXW7

- review_batch: proteostasis-batch-2026-06-13
- review_yaml: genes/human/FBXW7/FBXW7-ai-review.yaml
- PN workbook rows: 3

## PN row 1: Autophagy-Lysosome Pathway | Pre-initiation autophagy signaling | mTORC1 pathway, direct | Modulator of mTORC1 activity
- UniProt: Q969H0
- In branches: ALP, UPS
- Notes: F-box protein, member of SCF E3 ubiquitin ligase. Mediates ubiquitination and thereby degradation of SHOC2, which binds and activates RPTOR to inhibit mTORC1, thereby activating mTORC1 and suppressing autophagy.
- PN references (titles):
    - A Destiny for Degradation: Interplay between Cullin-RING E3 Ligases and Autophagy - ScienceDirect
    - The FBXW7-SHOC2-Raptor Axis Controls the Cross-Talks between the RAS-ERK and mTORC1 Signaling Pathways - ScienceDirect
- PN-node mapping records (path + ancestors):
    - [type] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, direct|Modulator of mTORC1 activity
        status=no_mapping scope= GO=[]
        rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
    - [group] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, direct
        status=no_mapping scope= GO=[]
        rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    - [class] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling
        status=context_only scope=too_broad_to_propagate GO=[GO:0010506 regulation of autophagy]
        rationale: This class organizes upstream signaling inputs to autophagy initiation. Because the subtree contains generic insulin, AMPK, mTORC1, nutrient-sensing, and miscellaneous signaling components, class-level propagation to regulation of autophagy would over-annotate many genes.
    - [branch] Autophagy-Lysosome Pathway
        status=no_mapping scope= GO=[]
        rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

## PN row 2: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul1 substrate receptor | F-box | WD40
- UniProt: Q969H0
- In branches: ALP, UPS
- Signature domains: IPR001810
- Auxiliary domains: IPR001680
- PN references (titles):
    - 15340381 / rev
- 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.

## PN row 3: Ubiquitin Proteasome System | Ubiquitin and UBL binding | E3 ligase | CUL1 receptor | idiosyncratic Ub binding / WD40
- UniProt: Q969H0
- In branches: ALP, UPS
- Signature domains: PMID: 21070969 (IPR001680)
- Auxiliary domains: IPR001810
- PN references (titles):
    - 21070969
- PN-node mapping records (path + ancestors):
    - [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase|CUL1 receptor|idiosyncratic Ub binding / WD40
        status=no_mapping scope= GO=[]
        rationale: Reviewed as a narrower enzyme-family, domain, or architecture subdivision already covered by a curated parent enzyme mapping. No additional direct GO mapping is needed at this node.
    - [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase|CUL1 receptor
        status=no_mapping scope= GO=[]
        rationale: Reviewed as a narrower enzyme-family, domain, or architecture subdivision already covered by a curated parent enzyme mapping. No additional direct GO mapping is needed at this node.
    - [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase
        status=mapped scope=ok_for_propagation_to_go GO=[GO:0061630 ubiquitin protein ligase activity]
        rationale: This PN group captures ubiquitin/UBL-binding factors that are E3 ligases. The shared molecular-function target is ubiquitin protein ligase activity.
    - [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
        status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
        rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
    - [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 (2)
- GO:1990756 ubiquitin-like ligase-substrate adaptor activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor
- GO:0061630 ubiquitin protein ligase activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase