PDCD6IP PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q8WUM4
- 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: PDCD6IP encodes ALIX/AIP1, a Bro1-domain ESCRT accessory adaptor that links cargo/adaptors and membrane-remodeling sites to CHMP4/ESCRT-III. ALIX supports MVB/late-endosomal cargo sorting, exosome biogenesis with the syndecan-syntenin pathway, basal autophagic flux and endolysosomal trafficking through ATG12-ATG3-associated regulation, and CEP55-dependent midbody cytokinesis. Viral budding is a well-supported pathogen-exploitation context, while endogenous ALIX roles center on ESCRT adaptor activity in endolysosomal, exosome, and cytokinetic membrane-remodeling pathways.
- Existing/core annotation action counts: ACCEPT: 28; KEEP_AS_NON_CORE: 25; MARK_AS_OVER_ANNOTATED: 32; MODIFY: 1
PN Consistency Summary
- Consistency: Largely consistent. The PN note (ALIX/ATG12-ATG3 recruits ESCRT-III for autophagosome closure) aligns with the review, which ACCEPTs GO:0016236 macroautophagy (ISS) on the strength of PMID:25686249 (ALIX required for basal autophagic flux). The autophagy-closure framing is supported. The leaf being
no_mapping (heterogeneous members) is consistent with the review not asserting an autophagy-specific ESCRT-III-localization MF for ALIX.
- PN story / NEW pressure: PN projects GO:0000045 autophagosome assembly (
more_specific_than_existing_goa — GOA/review have the broader GO:0016236 macroautophagy). For ALIX this is more defensible than for the MVB12 subunits because the gene-specific basal-autophagy evidence (PMID:25686249) exists, but the cited support is for basal autophagic flux/late-endosome function rather than phagophore sealing specifically. Conclusion: GO:0000045 is a plausible candidate (not pure over-reach), but the review's macroautophagy ACCEPT already captures the role; adding autophagosome assembly should be expert-gated, not auto-propagated.
- Evidence alignment: Shared: PMID:25686249 (ATG12-ATG3–ALIX) is a PN reference and the review's macroautophagy anchor. PN also cites closure-regulator and exosome/autophagy reviews; review independently supports MVB/exosome/cytokinesis (PMID:12860994, PMID:22660413, PMID:18641129). Good overlap on the autophagy link.
- Verdict: Consistent; PN autophagosome-assembly projection is a reasonable candidate but the curated macroautophagy ACCEPT already covers it. No edits required.
Full Consistency Review
- UniProt: Q8WUM4 · batch: proteostasis-pr-1217 · review status: COMPLETE
- PN placement:
ALP|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Localization of the ESCRT-III complex ; PN-node mapping: leaf no_mapping (members mix endosomal-sorting + SNARE genes); "Sealing" group mapped / ok_for_propagation / GO:0000045 autophagosome assembly; class context_only GO:0016236. Projected: GO:0000045 (more_specific_than_existing_goa).
- Consistency: Largely consistent. The PN note (ALIX/ATG12-ATG3 recruits ESCRT-III for autophagosome closure) aligns with the review, which ACCEPTs GO:0016236 macroautophagy (ISS) on the strength of PMID:25686249 (ALIX required for basal autophagic flux). The autophagy-closure framing is supported. The leaf being
no_mapping (heterogeneous members) is consistent with the review not asserting an autophagy-specific ESCRT-III-localization MF for ALIX.
- PN story / NEW pressure: PN projects GO:0000045 autophagosome assembly (
more_specific_than_existing_goa — GOA/review have the broader GO:0016236 macroautophagy). For ALIX this is more defensible than for the MVB12 subunits because the gene-specific basal-autophagy evidence (PMID:25686249) exists, but the cited support is for basal autophagic flux/late-endosome function rather than phagophore sealing specifically. Conclusion: GO:0000045 is a plausible candidate (not pure over-reach), but the review's macroautophagy ACCEPT already captures the role; adding autophagosome assembly should be expert-gated, not auto-propagated.
- Mapping strategy: Node scoping is sound. The
no_mapping leaf correctly avoids over-claiming; the "Sealing" group projecting GO:0000045 is acceptable as candidate for ALIX given basal-autophagy evidence, but should remain more_specific candidate rather than displacing the curated macroautophagy call.
- Evidence alignment: Shared: PMID:25686249 (ATG12-ATG3–ALIX) is a PN reference and the review's macroautophagy anchor. PN also cites closure-regulator and exosome/autophagy reviews; review independently supports MVB/exosome/cytokinesis (PMID:12860994, PMID:22660413, PMID:18641129). Good overlap on the autophagy link.
- Verdict: Consistent; PN autophagosome-assembly projection is a reasonable candidate but the curated macroautophagy ACCEPT already covers it. No edits required.
PN Dossier Context
- review_batch: proteostasis-pr-1217
- review_yaml: genes/human/PDCD6IP/PDCD6IP-ai-review.yaml
- PN workbook rows: 1
PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | Localization of the ESCRT-III complex
- UniProt: Q8WUM4
- In branches: ALP
- Notes: Binds to ATG13-ATG3 complexes to recruit ESCRT-III for autophagosome closure
- PN references (titles):
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
- Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells | Cell & Bioscience | Full Text (biomedcentral.com)
- ATG12–ATG3 interacts with Alix to promote basal autophagic flux and late endosome function | Nature Cell Biology
- PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Localization of the ESCRT-III complex
status=no_mapping scope= GO=[]
rationale: This PN leaf groups factors that affect ESCRT-III localization during sealing, but the current member set mixes endosomal sorting and SNARE trafficking genes rather than one clean shared autophagy-specific GO term.
- [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 (1)
- 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
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.