Rubcn (mouse, Q80U62) review notes
Sources
- Deep research: no
Rubcn-deep-research-*.md was present when this review was written; the review relies on cached publications, UniProt and the human RUBCN review.
- Martinez et al. 2015 (PMID:26098576, LAP/NOX2/Rubicon) and Martinez et al. 2016 (PMID:27096368, lupus-like disease in LAP-deficient mice) are both RETRACTED (retraction notes PMID:38438803 and PMID:36045298). They are not used as evidence for LAP or lupus-like phenotypes of Rubcn knockout mice.
Evidence synthesis
- Mouse Rubicon was identified in Beclin 1-EGFP complexes from mouse tissues and inhibits VPS34: PMID:19270693; PMID:19270693; overexpression gives PMID:19270693.
- Direct PI3P binding was tested and was negative: PMID:19270693, although Rubicon-positive structures are PI3P-enriched.
- RH domain binds Rab7-GTP: PMID:32632011. The structure argues against FYVE-like lipid binding: PMID:32632011.
- A 2026 bioRxiv preprint (PMID:42845427, abstract only) reports that the Rubicon PIKBD binds PI3KC3-C2 via the BECN1 BARA domain and that this interface accounts for Rubicon's negative effects: PMID:42845427. Preprint, so used as context only.
- Mouse genetics: PMID:30783089; PMID:27637015 (hepatocyte KO protects from HFD steatosis); PMID:35282767.
- Immunity (human/mouse macrophages, Jung lab): Rubicon promotes NADPH oxidase activation PMID:22423966 and feedback-inhibits CARD9 signalling PMID:22423967. Not in mouse GOA; not proposed as NEW (non-core, no mouse GOA rows).
PAINT (PTHR45971) assessment
- PTN002915566 (RUBCN clade, Euteleostomi): early endosome, late endosome, negative regulation of endocytosis, negative regulation of autophagosome maturation all sound for mouse Rubcn; mouse experimental data (PMID:19270693) independently confirm them.
- PTN002915557 (Eukaryota root): GO:1901981 seeded only by RUBCNL/Pacer (Q9H714, IDA PMID:28306502). For Rubicon proper it is contradicted by a negative pull-down and structural reasoning; MARK_AS_OVER_ANNOTATED. GO:0043231 (organelle) is generic and true but was not propagated to mouse Rubcn in this GOA file.
- Fly Rubicon (Q9W3C9) has the PIKBD (PF21054) and RH (PF13901) but lacks a RUN domain; worm Y56A3A.16 (G2HK09) has only the RH domain detected by Pfam. Neither has direct lipid-binding evidence; fly Rubicon localizes to Rab7-positive late endosomes/phagosomes in glia PMID:37248218, consistent with Rab7 rather than lipid targeting. Knockdown extends worm and fly lifespan PMID:30783089.
Actions
- GO:0005515 (EGFR, IPI) REMOVE; nucleoplasm ISO REMOVE; PI3K/AKT signalling MODIFY to GO:0141039; GO:1901981 IBA MARK_AS_OVER_ANNOTATED; cytosol KEEP_AS_NON_CORE; others ACCEPT.
- GO:0031267 small GTPase binding is proposed as NEW for human RUBCN (RH domain-Rab7-GTP crystal structure, PMID:32632011) but is deliberately not mirrored here: the structural and binding evidence is human-only, mouse Rubcn would inherit it by orthology (ISS/ISO from the human annotation once curated), so no NEW row is added for mouse; the Rab7 interaction is used only as mechanistic context for the late endosome/lysosome location and autophagosome-maturation rows.