MVB12A PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q96EY5
- 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: MVB12A is a metazoan ESCRT-I fourth subunit that complexes with TSG101, VPS28, and VPS37-family subunits. Its best-supported core cellular role is ESCRT-I-dependent sorting of ubiquitinated endosomal cargo into multivesicular bodies, supported by acidic phospholipid/ubiquitin binding, EGFR down-regulation context, and MVB12A-containing ESCRT-I structural evidence. Viral budding and virus maturation reflect pathogen exploitation of ESCRT machinery rather than the main endogenous MVB12A function.
- Existing/core annotation action counts: ACCEPT: 23; KEEP_AS_NON_CORE: 16; MARK_AS_OVER_ANNOTATED: 4; MODIFY: 3; UNDECIDED: 1
PN Consistency Summary
- Consistency: Partial tension. GO:0000813 ESCRT I complex is fully consistent (multiply ACCEPTed). But the review MARK_AS_OVER_ANNOTATED for GO:0016236 macroautophagy, stating the ESCRT/autophagy review (PMID:20588296) and the VPS28-interface structural assay (PMID:32424346) do NOT establish MVB12A as a core phagophore-closure factor. PN's
mapped/ok_for_propagation projection of GO:0000045 autophagosome assembly from the "Sealing" group therefore conflicts with the review's stance.
- PN story / NEW pressure: PN asserts MVB12A is involved in autophagophore sealing/autophagosome assembly — a role NOT in MVB12A's GOA and NOT added by the review. The review treats this as over-annotation pending MVB12A-specific phagophore-closure perturbation (the VPS37A evidence in PMID:31519728 is about a different ESCRT-I subunit). Conclusion: PN over-reaches at the gene level for GO:0000045; better left as a curator question, not a propagated annotation.
- Evidence alignment: Shared paper: PMID:32424346 (ESCRT-I helical assembly) is both the PN reference and the review's source for ESCRT-I/membrane-fission. PN's autophagy framing leans on PMID:20588296; review cites the same but downgrades it. Strong overlap on the structural evidence, divergence on the autophagy inference.
- Verdict: ESCRT-I membership consistent; PN's GO:0000045 autophagosome-assembly projection over-reaches per the review's own MARK_AS_OVER_ANNOTATED. Recommended edits: none to the gene YAML; flag the "Sealing" node so GO:0000045 is not auto-propagated to MVB12A without subunit-specific closure evidence.
Full Consistency Review
- UniProt: Q96EY5 · batch: proteostasis-pr-1217 · review status: COMPLETE
- PN placement:
ALP|...|Sealing of autophagophore membrane|ESCRT-I complex component and UPS|Ubiquitin and UBL binding|trafficking|ESCRT-I complex|idiosyncratic Ub binding ; PN-node mapping: ALP leaf mapped / GO:0000813 ESCRT I complex; ALP "Sealing" group mapped / ok_for_propagation / GO:0000045 autophagosome assembly; UPS nodes all no_mapping (class context_only GO:0140036). Projected: GO:0000813 (already_in_goa_exact), GO:0000045 (more_specific_than_existing_goa).
- Consistency: Partial tension. GO:0000813 ESCRT I complex is fully consistent (multiply ACCEPTed). But the review MARK_AS_OVER_ANNOTATED for GO:0016236 macroautophagy, stating the ESCRT/autophagy review (PMID:20588296) and the VPS28-interface structural assay (PMID:32424346) do NOT establish MVB12A as a core phagophore-closure factor. PN's
mapped/ok_for_propagation projection of GO:0000045 autophagosome assembly from the "Sealing" group therefore conflicts with the review's stance.
- PN story / NEW pressure: PN asserts MVB12A is involved in autophagophore sealing/autophagosome assembly — a role NOT in MVB12A's GOA and NOT added by the review. The review treats this as over-annotation pending MVB12A-specific phagophore-closure perturbation (the VPS37A evidence in PMID:31519728 is about a different ESCRT-I subunit). Conclusion: PN over-reaches at the gene level for GO:0000045; better left as a curator question, not a propagated annotation.
- Mapping strategy: This gene argues the "Sealing of autophagophore membrane" group's
ok_for_propagation (GO:0000045) is too aggressive for MVB12A specifically — the subunit rides in via complex membership, not demonstrated phagophore-closure function (cf. broader-term rejections). Recommend the node treat per-subunit projection of GO:0000045 as candidate, not automatic.
- Evidence alignment: Shared paper: PMID:32424346 (ESCRT-I helical assembly) is both the PN reference and the review's source for ESCRT-I/membrane-fission. PN's autophagy framing leans on PMID:20588296; review cites the same but downgrades it. Strong overlap on the structural evidence, divergence on the autophagy inference.
- Verdict: ESCRT-I membership consistent; PN's GO:0000045 autophagosome-assembly projection over-reaches per the review's own MARK_AS_OVER_ANNOTATED. Recommended edits: none to the gene YAML; flag the "Sealing" node so GO:0000045 is not auto-propagated to MVB12A without subunit-specific closure evidence.
PN Dossier Context
- review_batch: proteostasis-pr-1217
- review_yaml: genes/human/MVB12A/MVB12A-ai-review.yaml
- PN workbook rows: 2
PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component
- UniProt: Q96EY5
- In branches: ALP, UPS
- 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.
PN row 2: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | ESCRT-I complex | idiosyncratic Ub binding / other
- UniProt: Q96EY5
- In branches: ALP, UPS
- Signature domains: PMID: 20654576
- Auxiliary domains: (none)
- PN references (titles):
- PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|ESCRT-I complex|idiosyncratic Ub binding / other
status=no_mapping scope= GO=[]
rationale: Reviewed as a family, domain, architecture, or residual subdivision. The label is useful for PN taxonomy navigation but is not itself a GO annotation target; any functional assertion should come from a curated parent role or gene-level evidence.
- [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|ESCRT-I complex
status=no_mapping scope= GO=[]
rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking
status=no_mapping scope= GO=[]
rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
- [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 (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.