## ANKFY1

- **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.