VPS28 PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
• UniProt: Q9UK41
• AIGR review status: COMPLETE
• Review batch: proteostasis-pr-1217 (PR 1217)
• Batch change status: added

Source Files Checked

• AIGR review YAML: present - genes/human/VPS28/VPS28-ai-review.yaml
• AIGR review HTML: present - genes/human/VPS28/VPS28-ai-review.html
• Gene notes: present - genes/human/VPS28/VPS28-notes.md
• GOA TSV: present - genes/human/VPS28/VPS28-goa.tsv
• UniProt record: present - genes/human/VPS28/VPS28-uniprot.txt
• PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/VPS28.md
• PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/VPS28.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: VPS28 is a conserved core subunit of human ESCRT-I. It pairs with TSG101, a VPS37 paralog, and an MVB12/UBAP-family subunit to organize ESCRT-I for ubiquitin-dependent endosomal cargo sorting, multivesicular body assembly, reverse-topology membrane remodeling, and phagophore/autophagosome closure. Unlike TSG101, VPS28 is not well supported as a direct ubiquitin-binding protein; its core role is ESCRT-I structural/scaffold assembly and membrane-site recruitment.
• Existing/core annotation action counts: ACCEPT: 31; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 18; MODIFY: 3; NEW: 1

PN Consistency Summary

• Consistency: Strong agreement. Deep research/notes, review, and PN all treat VPS28 as a constitutive structural/scaffold ESCRT-I subunit acting in MVB sorting plus ESCRT-I-dependent phagophore/autophagosome closure. The review adds nuance the PN does not contradict: VPS28 itself does not bind ubiquitin (TSG101 UEV does), so it MARKs GO:0043130 over-annotated.
• PN story / NEW pressure: ESCRT-I membership (GO:0000813) is already_in_goa. For the autophagy role, GOA only has broad GO:0016236 macroautophagy; the review MODIFYs that to GO:0000045 autophagosome assembly AND adds GO:0000045 as a NEW annotation (IMP, PMID:32424346 helical-interface mutant → closure defect). This matches the PN projection exactly. Verdict: PN story is real and the review correctly adds the more specific GO:0000045 (new to direct GOA).
• Evidence alignment: PN cites only PMID:32424346. Review's autophagy evidence pairs PMID:32424346 with PMID:31519728 (VPS37A directs ESCRT recruitment for phagophore closure) and PMID:20588296 — broader and concordant. ESCRT-I/MVB core uses PMID:11134028/11916981/18005716/20654576/21757351. Good overlap, review is richer.
• Verdict: Consistent and well-supported; the VPS28 review is the model case for this ESCRT-I leaf — GO:0000045 NEW is justified and matches the PN mapping.

Full Consistency Review

• UniProt: Q9UK41 · batch: proteostasis-pr-1217 · review status: COMPLETE
• PN placement: ALP …|Sealing of autophagophore membrane|ESCRT-I complex component ; PN-node mapping: leaf mapped/ok_for_propagation GO:0000813 ESCRT I complex (already_in_goa_exact); group mapped GO:0000045 autophagosome assembly (more_specific_than_existing_goa).
• Consistency: Strong agreement. Deep research/notes, review, and PN all treat VPS28 as a constitutive structural/scaffold ESCRT-I subunit acting in MVB sorting plus ESCRT-I-dependent phagophore/autophagosome closure. The review adds nuance the PN does not contradict: VPS28 itself does not bind ubiquitin (TSG101 UEV does), so it MARKs GO:0043130 over-annotated.
• PN story / NEW pressure: ESCRT-I membership (GO:0000813) is already_in_goa. For the autophagy role, GOA only has broad GO:0016236 macroautophagy; the review MODIFYs that to GO:0000045 autophagosome assembly AND adds GO:0000045 as a NEW annotation (IMP, PMID:32424346 helical-interface mutant → closure defect). This matches the PN projection exactly. Verdict: PN story is real and the review correctly adds the more specific GO:0000045 (new to direct GOA).
• Mapping strategy: VPS28 legitimately supports the ALP leaf (GO:0000813) and group (GO:0000045) projections — unlike UBAP1/UMAD1 it has direct VPS28 closure evidence (PMID:31519728, PMID:32424346). Scope ok_for_propagation is justified; PN-projected GO:0000045 is appropriately narrower than parent macroautophagy and aligns with the review.
• Evidence alignment: PN cites only PMID:32424346. Review's autophagy evidence pairs PMID:32424346 with PMID:31519728 (VPS37A directs ESCRT recruitment for phagophore closure) and PMID:20588296 — broader and concordant. ESCRT-I/MVB core uses PMID:11134028/11916981/18005716/20654576/21757351. Good overlap, review is richer.
• Verdict: Consistent and well-supported; the VPS28 review is the model case for this ESCRT-I leaf — GO:0000045 NEW is justified and matches the PN mapping.

PN Dossier Context

• review_batch: proteostasis-pr-1217
• review_yaml: genes/human/VPS28/VPS28-ai-review.yaml
• PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component

• UniProt: Q9UK41
• In branches: ALP
• Notes: Component of the ESCRT-I complex, involved in autophagosome closure
• PN references (titles):
  • A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
• PN-node mapping records (path + ancestors):
  • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0000813 ESCRT I complex]
    rationale: This leaf is restricted to ESCRT-I components used in autophagophore sealing. The shared GO assertion is ESCRT I complex membership.
  • [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.

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:0000813 ESCRT I complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I 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.