VPS4A PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q9UN37
- AIGR review status: COMPLETE
- Review batch: proteostasis-pr-1217 (PR 1217)
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: VPS4A is a conserved AAA-family ATPase that recognizes membrane-associated ESCRT-III assemblies through its MIT domain and uses ATP hydrolysis to remodel and disassemble ESCRT-III polymers. This recycling function supports ESCRT-dependent membrane remodeling in MVB/endosomal cargo sorting and related topologically equivalent events, including cytokinetic abscission, nuclear-envelope sealing, viral budding, plasma membrane repair, and exosome release. The core function is ATP-driven ESCRT-III remodeling/disassembly rather than generic protein binding or membership in the ESCRT-III complex itself.
- Existing/core annotation action counts: ACCEPT: 52; KEEP_AS_NON_CORE: 47; MARK_AS_OVER_ANNOTATED: 31; MODIFY: 9; UNDECIDED: 2
PN Consistency Summary
- Consistency: CONTRADICTION on GO:0000815, and a labeling concern on goa_status. The review's central thesis (description + core_functions) is that VPS4A is the AAA ATPase that recognizes and disassembles ESCRT-III, NOT an ESCRT-III subunit; notes explicitly say "PN projection to GO:0000815 should not be added for VPS4A." The review instead asserts GO:1904903 ESCRT III complex disassembly (verified real via OLS) and GO:0016887 ATP hydrolysis. GOA contains no GO:0000815 or GO:0000045 — only GO:0016236 — so the projected goa_status "more_specific_than_existing_goa" is misleading (GO:0000815 would be a new, contested CC, not a refinement).
- PN story / NEW pressure: Mixed. PN's "ESCRT-III activity modulator" placement is biologically apt and matches the review's disassembly framing — but the microautophagy "ESCRT-III complex component" leaf miscategorizes VPS4A as a complex member. The accurate molecular story (ATP-driven ESCRT-III disassembly) is captured by the review's GO:1904903/GO:0016887; no new term needed.
- Evidence alignment: Partial. PN cites the MDPI autophagosome-closure review and PMID-bearing "CHMP2A as a regulator of phagophore closure" (Nat Commun). Review is built on VPS4-specific primary/structural literature (PMID:17928862, 18606141, 36604498, 20616062) not in PN.
- Verdict: ESCRT-III-modulator framing consistent; GO:0000815 projection contradicts the review (VPS4A disassembles, not member). Recommended edits: none to YAML; reclassify PN microautophagy leaf→GO:0000815 to context_only for VPS4A and drop/relabel the GO:0000815 and GO:0000045 projections.
Full Consistency Review
- UniProt: Q9UN37 · batch: proteostasis-pr-1217 · review status: COMPLETE
- PN placement: 2 rows, ALP — (1)
Autophagosome closure maturation and lysosome fusion → Sealing of autophagophore membrane → ESCRT-III complex activity modulator; (2) Microautophagy → General microautophagy machinery → ESCRT-III complex component. PN-node mapping: modulator leaf=context_only (GO:0000815, "should not project ESCRT-III membership to all members"); microautophagy-component leaf=mapped→GO:0000815; sealing group=mapped→GO:0000045; classes context_only (GO:0016236, GO:0016237). Projected: GO:0000045 (more_specific_than_existing_goa), GO:0000815 ESCRT III complex (more_specific_than_existing_goa).
- Consistency: CONTRADICTION on GO:0000815, and a labeling concern on goa_status. The review's central thesis (description + core_functions) is that VPS4A is the AAA ATPase that recognizes and disassembles ESCRT-III, NOT an ESCRT-III subunit; notes explicitly say "PN projection to GO:0000815 should not be added for VPS4A." The review instead asserts GO:1904903 ESCRT III complex disassembly (verified real via OLS) and GO:0016887 ATP hydrolysis. GOA contains no GO:0000815 or GO:0000045 — only GO:0016236 — so the projected goa_status "more_specific_than_existing_goa" is misleading (GO:0000815 would be a new, contested CC, not a refinement).
- PN story / NEW pressure: Mixed. PN's "ESCRT-III activity modulator" placement is biologically apt and matches the review's disassembly framing — but the microautophagy "ESCRT-III complex component" leaf miscategorizes VPS4A as a complex member. The accurate molecular story (ATP-driven ESCRT-III disassembly) is captured by the review's GO:1904903/GO:0016887; no new term needed.
- Mapping strategy: Change recommended. The microautophagy-component leaf→GO:0000815 should be context_only/no_mapping for VPS4A (as the sealing modulator leaf already correctly is), since VPS4A is not an ESCRT-III subunit. GO:0000815 over-reaches; this matches the rejected broader-projection precedent. GO:0000045 also unsupported here (review keeps autophagy rows MARK_AS_OVER_ANNOTATED / late-microautophagy UNDECIDED).
- Evidence alignment: Partial. PN cites the MDPI autophagosome-closure review and PMID-bearing "CHMP2A as a regulator of phagophore closure" (Nat Commun). Review is built on VPS4-specific primary/structural literature (PMID:17928862, 18606141, 36604498, 20616062) not in PN.
- Verdict: ESCRT-III-modulator framing consistent; GO:0000815 projection contradicts the review (VPS4A disassembles, not member). Recommended edits: none to YAML; reclassify PN microautophagy leaf→GO:0000815 to context_only for VPS4A and drop/relabel the GO:0000815 and GO:0000045 projections.
PN Dossier Context
- review_batch: proteostasis-pr-1217
- review_yaml: genes/human/VPS4A/VPS4A-ai-review.yaml
- PN workbook rows: 2
PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-III complex activity modulator
- UniProt: Q9UN37
- In branches: ALP
- Notes: VPS4A and VPS4B are AAA+ ATPases that work with ESCRT-III in membrane scission and autophagosome closure.
- PN references (titles):
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
- An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure | Nature Communications
- PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex activity modulator
status=context_only scope=too_broad_to_propagate GO=[GO:0000815 ESCRT III complex]
rationale: Reviewed as an ESCRT-III activity modulator. It is related to ESCRT-III but should not project ESCRT-III complex membership to all members.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [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: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component
- UniProt: Q9UN37
- In branches: ALP
- PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000815 ESCRT III complex]
rationale: This leaf is a component bucket for ESCRT-III machinery used in microautophagy contexts. The shared GO assertion is ESCRT III complex membership.
- [group] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery
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|Microautophagy
status=context_only scope=too_broad_to_propagate GO=[GO:0016237 microautophagy]
rationale: The class names a real GO process, but the subtree includes machinery components and mitochondrion-derived-vesicle contexts as well as process labels. Propagation is restricted to narrower nodes.
- [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.
Projected GO annotations (2)
- GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
- GO:0000815 ESCRT III complex | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component
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.