RUBCNL PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q9H714
- 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: RUBCNL encodes PACER, a Rubicon-like autophagy enhancer that acts at late autophagosome maturation. It is recruited to STX17-positive autophagosome membranes, interacts with UVRAG/STX17, promotes recruitment of PI3K/PI3KC3 and HOPS complexes, stimulates Vps34/PI3KC3-dependent PtdIns(3)P production, and supports autophagosome-endosome/lysosome fusion. RUBCNL functions as an autophagosome-maturation adaptor/recruitment factor associated with PI3KC3-C2 and HOPS.
- Existing/core annotation action counts: ACCEPT: 13; KEEP_AS_NON_CORE: 1; MARK_AS_OVER_ANNOTATED: 2; MODIFY: 1; NEW: 2
PN Consistency Summary
- Consistency: A directionality mismatch in the shared PN Notes. The PN Notes string is "Member of class III PI3K complex 2 that binds to UVRAG and inhibits activity" — copied from the Rubicon row — but RUBCNL/PACER is a POSITIVE late-autophagy regulator that stimulates Vps34 activity and recruits PI3KC3/HOPS (PMID:28306502, 30704899; UniProt). Review and notes are correct (positive); the PN workbook Notes field is wrong for this gene. Flag.
- PN story / NEW pressure: PN asserts GO:0034272 membership absent from GOA (
new_to_goa). Review adds GO:0034272 part_of as action NEW (PMID:28306502), plus GO:0030674 protein-macromolecule adaptor activity (NEW) replacing generic protein binding. GO:0034272 verified real. Verdict: ADD GO:0034272 (review already did) + adaptor MF — aligned with and richer than PN.
- Evidence alignment: Divergence. PN cites Annual Review, a cardiovascular review, and PMID:19270696 (the Atg14L/Rubicon paper) — none of which is PACER-specific; PMID:19270696 is not cited in the RUBCNL review (and is not PACER-relevant). Review uses the correct primary literature: PMID:28306502 (PACER discovery), 30704899 (mTORC1/TIP60). PN reference set is essentially a shared-branch boilerplate, weakly matched to this gene.
- Verdict: Consistent on biology, but the PN workbook Notes mis-state PACER as inhibitory ("inhibits activity") — it is a positive regulator. NEW GO:0034272 matches PN projection (verified). Recommended edits: none to the gene YAML (correct); upstream PN-workbook Notes for RUBCNL should be corrected from "inhibits activity" to a positive/recruitment role, and the PN reference list (PMID:19270696) is not PACER-specific.
Full Consistency Review
- UniProt: Q9H714 · batch: proteostasis-pr-1217 · review status: COMPLETE
- PN placement:
ALP|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Class 3 PI3K complex 2 component ; PN-node mapping: type leaf mapped, ok_for_propagation_to_go → GO:0034272, goa_status new_to_goa; ancestors GO:0035032 / GO:0016236 context_only.
- Consistency: A directionality mismatch in the shared PN Notes. The PN Notes string is "Member of class III PI3K complex 2 that binds to UVRAG and inhibits activity" — copied from the Rubicon row — but RUBCNL/PACER is a POSITIVE late-autophagy regulator that stimulates Vps34 activity and recruits PI3KC3/HOPS (PMID:28306502, 30704899; UniProt). Review and notes are correct (positive); the PN workbook Notes field is wrong for this gene. Flag.
- PN story / NEW pressure: PN asserts GO:0034272 membership absent from GOA (
new_to_goa). Review adds GO:0034272 part_of as action NEW (PMID:28306502), plus GO:0030674 protein-macromolecule adaptor activity (NEW) replacing generic protein binding. GO:0034272 verified real. Verdict: ADD GO:0034272 (review already did) + adaptor MF — aligned with and richer than PN.
- Mapping strategy: Supports (does not change) the C2-component → GO:0034272 mapping. As with RUBCN, PACER recruits/associates with PI3KC3-C2 rather than being a defined stoichiometric subunit, so
part_of is defensible but borderline (review flags this in suggested_questions). PN-projected term coincides with the review's NEW term.
- Evidence alignment: Divergence. PN cites Annual Review, a cardiovascular review, and PMID:19270696 (the Atg14L/Rubicon paper) — none of which is PACER-specific; PMID:19270696 is not cited in the RUBCNL review (and is not PACER-relevant). Review uses the correct primary literature: PMID:28306502 (PACER discovery), 30704899 (mTORC1/TIP60). PN reference set is essentially a shared-branch boilerplate, weakly matched to this gene.
- Verdict: Consistent on biology, but the PN workbook Notes mis-state PACER as inhibitory ("inhibits activity") — it is a positive regulator. NEW GO:0034272 matches PN projection (verified). Recommended edits: none to the gene YAML (correct); upstream PN-workbook Notes for RUBCNL should be corrected from "inhibits activity" to a positive/recruitment role, and the PN reference list (PMID:19270696) is not PACER-specific.
PN Dossier Context
- review_batch: proteostasis-pr-1217
- review_yaml: genes/human/RUBCNL/RUBCNL-ai-review.yaml
- PN workbook rows: 1
PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Class 3 PI3K complex 2, direct | Class 3 PI3K complex 2 component
- UniProt: Q9H714
- In branches: ALP
- Notes: Member of class III PI3K complex 2 that binds to UVRAG and inhibits activity
- PN references (titles):
- Mammalian Autophagy: How Does It Work? | Annual Review of Biochemistry (annualreviews.org)
- role of autophagy in cardiovascular pathology | Cardiovascular Research | Oxford Academic (oup.com)
- Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages | Nature Cell Biology
- PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Class 3 PI3K complex 2 component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II]
rationale: This PN type denotes component membership in the direct class III PI3K complex 2 module used during autophagosome maturation and lysosome fusion. The corresponding GO complex term is the right propagation target.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct
status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
- [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:0034272 phosphatidylinositol 3-kinase complex, class III, type II | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Class 3 PI3K complex 2 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.