ANKFY1 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q9P2R3
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-03 (PR 1366)
- Batch change status: added
Source Files Checked
Deep Research Files
AIGR Review Snapshot
- Description: ANKFY1 encodes Rabankyrin-5, a large ankyrin-repeat, BTB/POZ, and FYVE-domain protein that acts on PI3P- and Rab5-positive endosomal membranes. It binds activated Rab5-family GTPases and phosphatidylinositol phosphate lipids to regulate early endosome fusion, macropinocytosis, retromer-dependent endosome-to-Golgi and Golgi-to-lysosome trafficking, and receptor internalization. Recent work shows that ANKFY1 also recruits and stabilizes ATG2A on PI3P-rich endosomal membranes during autophagy, promoting ATG2A-mediated lipid transfer from endosomes to phagophores for autophagosome growth and completion.
- Existing/core annotation action counts: ACCEPT: 22; KEEP_AS_NON_CORE: 9; MODIFY: 4; NEW: 1; UNDECIDED: 2
PN Consistency Summary
- Consistency: CONTRADICTION (placement-level). PN places ANKFY1 in UPS as a Cul3 substrate receptor (BTB/ankyrin domain architecture), but DR ↔ notes ↔ review YAML all curate ANKFY1 as a PI3P-/Rab5-binding endosomal effector (Rabankyrin-5) and ATG2A-bridging autophagy factor. GOA has NO ubiquitin-ligase/CUL3 terms (only GO:0031267 Rab5 binding, GO:1901981 PI3P binding). The UPS placement rests on domain signature (BTB-BACK/ankyrin), not function.
- PN story / NEW pressure: PN's sole projected term GO:1990756 (verified real, new_to_goa): review explicitly REJECTS — no validated CUL3 membership, substrate recognition, or adaptor activity for ANKFY1; the BTB region is present but not functionally ubiquitin-ligase. Over-reaches. Instead the review ADDS GO:0000045 autophagosome assembly (verified real;
action: NEW, IMP, PMID:38622126 — ANKFY1 depletion impairs autophagosome growth, enhances ATG2A lipid transfer). The genuine proteostasis link is ALP (autophagosome formation), not UPS.
- Evidence alignment: PN cites PMID:15071497, 23912815 (titles only, generic). Review/notes anchor on PMID:15328530 (Rabankyrin-5/Rab5/PI3P), 22284051 (EHD1/retromer/M6PR), 24102721 (RhoD), and the key PMID:38622126 (ATG2A). No overlap with PN's cited PMIDs — divergent evidence base reflecting the placement conflict.
- Verdict: PN UPS/Cul3 placement and GO:1990756 projection over-reach; review correctly rejects and instead adds GO:0000045 (ALP). Domain-driven mis-placement.
Full Consistency Review
- UniProt: Q9P2R3 (Rabankyrin-5) · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
- PN placement: 1 row, UPS.
Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor|BTB-BACK, variant|ankyrin. PN-node mapping: group (Cul3 substrate receptor)=mapped→GO:1990756 ubiquitin-like ligase-substrate adaptor activity (new_to_goa); class (E3 ligases)=context_only→GO:0061630; subtype/type/branch=no_mapping.
- Consistency: CONTRADICTION (placement-level). PN places ANKFY1 in UPS as a Cul3 substrate receptor (BTB/ankyrin domain architecture), but DR ↔ notes ↔ review YAML all curate ANKFY1 as a PI3P-/Rab5-binding endosomal effector (Rabankyrin-5) and ATG2A-bridging autophagy factor. GOA has NO ubiquitin-ligase/CUL3 terms (only GO:0031267 Rab5 binding, GO:1901981 PI3P binding). The UPS placement rests on domain signature (BTB-BACK/ankyrin), not function.
- PN story / NEW pressure: PN's sole projected term GO:1990756 (verified real, new_to_goa): review explicitly REJECTS — no validated CUL3 membership, substrate recognition, or adaptor activity for ANKFY1; the BTB region is present but not functionally ubiquitin-ligase. Over-reaches. Instead the review ADDS GO:0000045 autophagosome assembly (verified real;
action: NEW, IMP, PMID:38622126 — ANKFY1 depletion impairs autophagosome growth, enhances ATG2A lipid transfer). The genuine proteostasis link is ALP (autophagosome formation), not UPS.
- Mapping strategy: ANKFY1 should be EXCLUDED from the Cul3-substrate-receptor GO:1990756 projection (domain-only mis-bucketing, analogous to the broader/wrong-bucket precedents). Its proteostasis relevance belongs in the autophagy branch via ATG2A-mediated phagophore growth.
- Evidence alignment: PN cites PMID:15071497, 23912815 (titles only, generic). Review/notes anchor on PMID:15328530 (Rabankyrin-5/Rab5/PI3P), 22284051 (EHD1/retromer/M6PR), 24102721 (RhoD), and the key PMID:38622126 (ATG2A). No overlap with PN's cited PMIDs — divergent evidence base reflecting the placement conflict.
- Verdict: PN UPS/Cul3 placement and GO:1990756 projection over-reach; review correctly rejects and instead adds GO:0000045 (ALP). Domain-driven mis-placement.
- Recommended edits: none to ANKFY1-ai-review.yaml. [MAP] exclude ANKFY1 from the Cul3-substrate-receptor GO:1990756 projection (no CUL3/adaptor evidence; function is Rab5/PI3P endosomal + ATG2A autophagy). Consider re-homing ANKFY1's proteostasis placement to ALP.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-03
- review_yaml: genes/human/ANKFY1/ANKFY1-ai-review.yaml
- PN workbook rows: 1
PN row 1: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul3 substrate receptor | BTB-BACK, variant | ankyrin
- UniProt: Q9P2R3
- In branches: UPS
- Signature domains: IPR000210, IPR049763
- Auxiliary domains: IPR002110
- PN references (titles):
- 15071497 / rev
- 23912815 / rev
- PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor|BTB-BACK, variant|ankyrin
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|Cul3 substrate receptor|BTB-BACK, variant
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|Cul3 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|Cul3 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.