VPS4B PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
• UniProt: O75351
• AIGR review status: COMPLETE
• Review batch: proteostasis-pr-1217 (PR 1217)
• Batch change status: added

Source Files Checked

• AIGR review YAML: present - genes/human/VPS4B/VPS4B-ai-review.yaml
• AIGR review HTML: present - genes/human/VPS4B/VPS4B-ai-review.html
• Gene notes: present - genes/human/VPS4B/VPS4B-notes.md
• GOA TSV: present - genes/human/VPS4B/VPS4B-goa.tsv
• UniProt record: present - genes/human/VPS4B/VPS4B-uniprot.txt
• PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/VPS4B.md
• PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/VPS4B.md
• PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
• PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

• No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

• Description: VPS4B is a conserved AAA-family ATPase that recognizes ESCRT-III assemblies through its MIT domain and uses ATP hydrolysis to remodel and disassemble ESCRT-III polymers. Direct biochemical evidence shows VPS4 binding to and disassembly of CHMP2A-CHMP3 helical tubes upon ATP hydrolysis. This core activity supports endosomal/MVB cargo sorting and related ESCRT membrane-remodeling outputs, including cytokinesis, viral budding, plasma membrane repair, and exosome secretion. The core function is ATP-dependent ESCRT-III remodeling/disassembly rather than generic protein binding or ESCRT-III complex membership.
• Existing/core annotation action counts: ACCEPT: 30; KEEP_AS_NON_CORE: 32; MARK_AS_OVER_ANNOTATED: 25; MODIFY: 6; NEW: 1; UNDECIDED: 1

PN Consistency Summary

• Consistency: CONTRADICTION on GO:0000815, plus goa_status concern (identical to VPS4A). Review thesis: VPS4B is the AAA ATPase that binds inside CHMP2A-CHMP3 tubes and disassembles ESCRT-III on ATP hydrolysis (direct biochemistry, PMID:18687924), NOT an ESCRT-III subunit; notes state "PN projection to GO:0000815 should not be added for VPS4B." Review instead asserts GO:1904903 ESCRT III complex disassembly (verified) + GO:0016887. GOA has GO:0016236/0006914/0061738/0097352 but no GO:0000815 or GO:0000045, so projecting GO:0000815 as "more_specific_than_existing_goa" mislabels a contested new CC as a refinement.
• PN story / NEW pressure: Mixed. "ESCRT-III activity modulator" placement matches the review; the microautophagy "ESCRT-III complex component" leaf miscategorizes VPS4B as a member. Accurate story captured by GO:1904903/GO:0016887; no new term needed. (Review keeps the GOA late-endosomal-microautophagy row as UNDECIDED, autophagy/autophagosome-maturation/macroautophagy as MARK_AS_OVER_ANNOTATED.)
• Evidence alignment: Partial. PN cites the MDPI closure review + "CHMP2A as a regulator of phagophore closure" (Nat Commun). Review draws on VPS4B-specific primary work (PMID:18687924, 18606141, 15024011, 16757520, 20616062, 24105262) not in PN.
• Verdict: ESCRT-III-modulator framing consistent; GO:0000815 projection contradicts the review (VPS4B disassembles, not member). Recommended edits: none to YAML; reclassify PN microautophagy leaf→GO:0000815 to context_only for VPS4B and drop/relabel the GO:0000815 and GO:0000045 projections.

Full Consistency Review

• UniProt: O75351 · 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); 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, plus goa_status concern (identical to VPS4A). Review thesis: VPS4B is the AAA ATPase that binds inside CHMP2A-CHMP3 tubes and disassembles ESCRT-III on ATP hydrolysis (direct biochemistry, PMID:18687924), NOT an ESCRT-III subunit; notes state "PN projection to GO:0000815 should not be added for VPS4B." Review instead asserts GO:1904903 ESCRT III complex disassembly (verified) + GO:0016887. GOA has GO:0016236/0006914/0061738/0097352 but no GO:0000815 or GO:0000045, so projecting GO:0000815 as "more_specific_than_existing_goa" mislabels a contested new CC as a refinement.
• PN story / NEW pressure: Mixed. "ESCRT-III activity modulator" placement matches the review; the microautophagy "ESCRT-III complex component" leaf miscategorizes VPS4B as a member. Accurate story captured by GO:1904903/GO:0016887; no new term needed. (Review keeps the GOA late-endosomal-microautophagy row as UNDECIDED, autophagy/autophagosome-maturation/macroautophagy as MARK_AS_OVER_ANNOTATED.)
• Mapping strategy: Change recommended (same as VPS4A). Microautophagy-component leaf→GO:0000815 should be context_only/no_mapping for VPS4B (consistent with the sibling modulator leaf), as VPS4B is not an ESCRT-III subunit. GO:0000815 over-reaches per the rejected broader-projection precedent; GO:0000045 also unsupported (review does not add it).
• Evidence alignment: Partial. PN cites the MDPI closure review + "CHMP2A as a regulator of phagophore closure" (Nat Commun). Review draws on VPS4B-specific primary work (PMID:18687924, 18606141, 15024011, 16757520, 20616062, 24105262) not in PN.
• Verdict: ESCRT-III-modulator framing consistent; GO:0000815 projection contradicts the review (VPS4B disassembles, not member). Recommended edits: none to YAML; reclassify PN microautophagy leaf→GO:0000815 to context_only for VPS4B and drop/relabel the GO:0000815 and GO:0000045 projections.

PN Dossier Context

• review_batch: proteostasis-pr-1217
• review_yaml: genes/human/VPS4B/VPS4B-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: O75351
• 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: O75351
• 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.