Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000421 autophagosome membrane	IBA GO_REF:0000033	ACCEPT	Summary: Autophagosome membrane localization is supported and central to PACER late-autophagy function. Reason: RUBCNL/PACER is recruited to late autophagic/autophagosome membranes and uses STX17-positive autophagosomes as the platform for PI3KC3 and HOPS recruitment. Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Cytoplasmic vesicle, autophagosome membrane file:human/RUBCNL/RUBCNL-uniprot.txt Associates with late autophagic structure file:human/RUBCNL/RUBCNL-uniprot.txt Recruitment to autophagosome membrane is promoted by autophagic stimuli PMID:28306502 Pacer localizes to autophagic structures
GO:0061909 autophagosome-lysosome fusion	IBA GO_REF:0000033	ACCEPT	Summary: Autophagosome-lysosome fusion is supported as a core late-autophagy process for RUBCNL. Reason: PACER recruits PI3KC3 and HOPS complexes at STX17-positive autophagosomes, supporting fusion specificity with late endosomes/lysosomes. Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:28306502 HOPS complex mediates the fusion of intracellular vesicles to lysosome file:human/RUBCNL/RUBCNL-uniprot.txt regulate the fusion specificity of autophagosomes with late endosomes/lysosomes file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17
GO:0061910 autophagosome-endosome fusion	IBA GO_REF:0000033	ACCEPT	Summary: Autophagosome-endosome fusion is supported as part of the same late maturation/fusion role. Reason: The curated mechanism places RUBCNL at STX17-positive autophagosomes where it recruits PI3KC3 and HOPS machinery to regulate fusion with late endosomal/lysosomal compartments. Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:28306502 HOPS complex mediates the fusion of intracellular vesicles to lysosome file:human/RUBCNL/RUBCNL-uniprot.txt regulate the fusion specificity of autophagosomes with late endosomes/lysosomes file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17
GO:0097352 autophagosome maturation	IBA GO_REF:0000033	ACCEPT	Summary: Autophagosome maturation is the central RUBCNL biological-process annotation. Reason: Both functional papers and UniProt support PACER as a positive regulator of late autophagosome maturation through STX17, PI3KC3, HOPS, and regulated phosphorylation/acetylation. Supporting Evidence: PMID:28306502 positively regulates autophagosome maturation PMID:28306502 stimulate Vps34 kinase activity PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:30704899 modulate autophagosome maturation through Pacer PMID:30704899 facilitates HOPS complex recruitment PMID:30704899 required for autophagosome maturation and lipid droplet clearance file:human/RUBCNL/RUBCNL-uniprot.txt promotes autophagosome maturation file:human/RUBCNL/RUBCNL-uniprot.txt promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
GO:1901981 phosphatidylinositol phosphate binding	IBA GO_REF:0000033	MODIFY	Summary: The broad phosphatidylinositol phosphate binding term is true but should be replaced by specific lipid-binding terms. Reason: RUBCNL has IDA-supported binding to PtdIns(3)P, PtdIns(4)P, and PtdIns(5)P, so the inherited generic term is less informative than the specific existing annotations. Proposed replacements: phosphatidylinositol-3-phosphate binding phosphatidylinositol-4-phosphate binding phosphatidylinositol-5-phosphate binding Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Binds phosphoinositides phosphatidylinositol 3-phosphate file:human/RUBCNL/RUBCNL-uniprot.txt GO:0032266; F:phosphatidylinositol-3-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0070273; F:phosphatidylinositol-4-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0010314; F:phosphatidylinositol-5-phosphate binding
GO:0000421 autophagosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Autophagosome membrane localization is supported and central to PACER late-autophagy function. Reason: RUBCNL/PACER is recruited to late autophagic/autophagosome membranes and uses STX17-positive autophagosomes as the platform for PI3KC3 and HOPS recruitment. Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Cytoplasmic vesicle, autophagosome membrane file:human/RUBCNL/RUBCNL-uniprot.txt Associates with late autophagic structure file:human/RUBCNL/RUBCNL-uniprot.txt Recruitment to autophagosome membrane is promoted by autophagic stimuli PMID:28306502 Pacer localizes to autophagic structures
GO:0000421 autophagosome membrane	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: Autophagosome membrane localization is supported and central to PACER late-autophagy function. Reason: RUBCNL/PACER is recruited to late autophagic/autophagosome membranes and uses STX17-positive autophagosomes as the platform for PI3KC3 and HOPS recruitment. Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Cytoplasmic vesicle, autophagosome membrane file:human/RUBCNL/RUBCNL-uniprot.txt Associates with late autophagic structure file:human/RUBCNL/RUBCNL-uniprot.txt Recruitment to autophagosome membrane is promoted by autophagic stimuli PMID:28306502 Pacer localizes to autophagic structures
GO:0005515 protein binding	IPI PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	MARK AS OVER ANNOTATED	Summary: The interaction evidence is real, but generic protein binding obscures the PACER adaptor/recruitment function. Reason: RUBCNL interaction data should be represented by the specific STX17/UVRAG-dependent adaptor role in PI3KC3/HOPS recruitment and autophagosome maturation, not by generic protein binding. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:30704899 disrupt the association of Pacer with Stx17 and the HOPS complex PMID:30704899 facilitates HOPS complex recruitment file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with UVRAG file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17 file:human/RUBCNL/RUBCNL-uniprot.txt association with the PI3K/PI3KC3 and HOPS complexes
GO:0005515 protein binding	IPI PMID:30704899 Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Re...	MARK AS OVER ANNOTATED	Summary: The interaction evidence is real, but generic protein binding obscures the PACER adaptor/recruitment function. Reason: RUBCNL interaction data should be represented by the specific STX17/UVRAG-dependent adaptor role in PI3KC3/HOPS recruitment and autophagosome maturation, not by generic protein binding. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:30704899 disrupt the association of Pacer with Stx17 and the HOPS complex PMID:30704899 facilitates HOPS complex recruitment file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with UVRAG file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17 file:human/RUBCNL/RUBCNL-uniprot.txt association with the PI3K/PI3KC3 and HOPS complexes
GO:0010314 phosphatidylinositol-5-phosphate binding	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: phosphatidylinositol-5-phosphate binding is directly supported and contributes to autophagosome-membrane recruitment/function. Reason: The discovery study and UniProt support phosphoinositide binding by PACER, including PtdIns(3)P, PtdIns(4)P, and PtdIns(5)P. Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Binds phosphoinositides phosphatidylinositol 3-phosphate file:human/RUBCNL/RUBCNL-uniprot.txt GO:0032266; F:phosphatidylinositol-3-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0070273; F:phosphatidylinositol-4-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0010314; F:phosphatidylinositol-5-phosphate binding
GO:0019216 regulation of lipid metabolic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Regulation of lipid metabolic process is supported as downstream organismal physiology, not the core PN molecular role. Reason: The direct human evidence centers on autophagosome maturation; lipid and glycogen homeostasis are described as additional or by-similarity biology downstream of PACER-dependent autophagy. Supporting Evidence: PMID:30704899 required for autophagosome maturation and lipid droplet clearance file:human/RUBCNL/RUBCNL-uniprot.txt acts as a regulator of lipid and glycogen homeostasis file:human/RUBCNL/RUBCNL-uniprot.txt Acetylated by KAT5/TIP60 under autophagy induction
GO:0032266 phosphatidylinositol-3-phosphate binding	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: phosphatidylinositol-3-phosphate binding is directly supported and contributes to autophagosome-membrane recruitment/function. Reason: The discovery study and UniProt support phosphoinositide binding by PACER, including PtdIns(3)P, PtdIns(4)P, and PtdIns(5)P. Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Binds phosphoinositides phosphatidylinositol 3-phosphate file:human/RUBCNL/RUBCNL-uniprot.txt GO:0032266; F:phosphatidylinositol-3-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0070273; F:phosphatidylinositol-4-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0010314; F:phosphatidylinositol-5-phosphate binding
GO:0061909 autophagosome-lysosome fusion	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: Autophagosome-lysosome fusion is supported as a core late-autophagy process for RUBCNL. Reason: PACER recruits PI3KC3 and HOPS complexes at STX17-positive autophagosomes, supporting fusion specificity with late endosomes/lysosomes. Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:28306502 HOPS complex mediates the fusion of intracellular vesicles to lysosome file:human/RUBCNL/RUBCNL-uniprot.txt regulate the fusion specificity of autophagosomes with late endosomes/lysosomes file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17
GO:0061910 autophagosome-endosome fusion	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: Autophagosome-endosome fusion is supported as part of the same late maturation/fusion role. Reason: The curated mechanism places RUBCNL at STX17-positive autophagosomes where it recruits PI3KC3 and HOPS machinery to regulate fusion with late endosomal/lysosomal compartments. Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:28306502 HOPS complex mediates the fusion of intracellular vesicles to lysosome file:human/RUBCNL/RUBCNL-uniprot.txt regulate the fusion specificity of autophagosomes with late endosomes/lysosomes file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17
GO:0070273 phosphatidylinositol-4-phosphate binding	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: phosphatidylinositol-4-phosphate binding is directly supported and contributes to autophagosome-membrane recruitment/function. Reason: The discovery study and UniProt support phosphoinositide binding by PACER, including PtdIns(3)P, PtdIns(4)P, and PtdIns(5)P. Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Binds phosphoinositides phosphatidylinositol 3-phosphate file:human/RUBCNL/RUBCNL-uniprot.txt GO:0032266; F:phosphatidylinositol-3-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0070273; F:phosphatidylinositol-4-phosphate binding file:human/RUBCNL/RUBCNL-uniprot.txt GO:0010314; F:phosphatidylinositol-5-phosphate binding
GO:0097352 autophagosome maturation	IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	ACCEPT	Summary: Autophagosome maturation is the central RUBCNL biological-process annotation. Reason: Both functional papers and UniProt support PACER as a positive regulator of late autophagosome maturation through STX17, PI3KC3, HOPS, and regulated phosphorylation/acetylation. Supporting Evidence: PMID:28306502 positively regulates autophagosome maturation PMID:28306502 stimulate Vps34 kinase activity PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:30704899 modulate autophagosome maturation through Pacer PMID:30704899 facilitates HOPS complex recruitment PMID:30704899 required for autophagosome maturation and lipid droplet clearance file:human/RUBCNL/RUBCNL-uniprot.txt promotes autophagosome maturation file:human/RUBCNL/RUBCNL-uniprot.txt promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
GO:0097352 autophagosome maturation	IDA PMID:30704899 Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Re...	ACCEPT	Summary: Autophagosome maturation is the central RUBCNL biological-process annotation. Reason: Both functional papers and UniProt support PACER as a positive regulator of late autophagosome maturation through STX17, PI3KC3, HOPS, and regulated phosphorylation/acetylation. Supporting Evidence: PMID:28306502 positively regulates autophagosome maturation PMID:28306502 stimulate Vps34 kinase activity PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:30704899 modulate autophagosome maturation through Pacer PMID:30704899 facilitates HOPS complex recruitment PMID:30704899 required for autophagosome maturation and lipid droplet clearance file:human/RUBCNL/RUBCNL-uniprot.txt promotes autophagosome maturation file:human/RUBCNL/RUBCNL-uniprot.txt promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
GO:0030674 protein-macromolecule adaptor activity	IPI PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	NEW	Summary: PACER has a supported adaptor/recruitment role at STX17-positive autophagosomes. Reason: Add this as a more informative molecular-function annotation than generic protein binding. RUBCNL links STX17-positive autophagosomes with UVRAG, PI3KC3, and HOPS machinery to drive autophagosome maturation. Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 anchoring to the autophagosomal SNARE Stx17 PMID:30704899 disrupt the association of Pacer with Stx17 and the HOPS complex PMID:30704899 facilitates HOPS complex recruitment file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with UVRAG file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17 file:human/RUBCNL/RUBCNL-uniprot.txt association with the PI3K/PI3KC3 and HOPS complexes
GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II	IPI PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl...	NEW	Summary: RUBCNL should be added as a PI3KC3-C2-associated regulatory/adaptor context component. Reason: The PN projection highlights missing PI3KC3-C2 context, and the functional evidence shows PACER/UVRAG-dependent recruitment and activation of PI3KC3 at autophagosomes during late autophagy. Supporting Evidence: PMID:28306502 recruits PI3KC3 and HOPS complexes PMID:28306502 stimulate Vps34 kinase activity file:human/RUBCNL/RUBCNL-uniprot.txt promotes the recruitment of PI3K/PI3KC3 and HOPS complexes file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with UVRAG

Core Functions

PACER/RUBCNL acts as a STX17-anchored autophagosome adaptor that recruits UVRAG-associated PI3KC3-C2 and HOPS machinery, stimulates Vps34/PI3KC3-dependent PtdIns(3)P production, and promotes late autophagosome maturation and fusion with endolysosomal compartments.

Molecular Function:

protein-macromolecule adaptor activity

Directly Involved In:

autophagosome maturation autophagosome-lysosome fusion autophagosome-endosome fusion

Cellular Locations:

autophagosome membrane

In Complex:

phosphatidylinositol 3-kinase complex, class III, type II

Supporting Evidence:

PMID:28306502
positively regulates autophagosome maturation
PMID:28306502
stimulate Vps34 kinase activity
PMID:28306502
recruits PI3KC3 and HOPS complexes
PMID:28306502
anchoring to the autophagosomal SNARE Stx17
PMID:30704899
facilitates HOPS complex recruitment
PMID:30704899
required for autophagosome maturation and lipid droplet clearance
file:human/RUBCNL/RUBCNL-uniprot.txt
promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
file:human/RUBCNL/RUBCNL-uniprot.txt
Interacts with UVRAG
file:human/RUBCNL/RUBCNL-uniprot.txt
Interacts with STX17
file:human/RUBCNL/RUBCNL-uniprot.txt
Cytoplasmic vesicle, autophagosome membrane

References

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:28306502

Pacer Mediates the Function of Class III PI3K and HOPS Complexes in Autophagosome Maturation by Engaging Stx17.

PMID:30704899

Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Regulation of Autophagosome Maturation and Lipid Metabolism.

file:human/RUBCNL/RUBCNL-uniprot.txt

UniProtKB record for human RUBCNL

file:human/RUBCNL/RUBCNL-notes.md

RUBCNL review notes

Suggested Experiments

Experiment: Use RUBCNL knockout/rescue cells with STX17-binding, UVRAG-binding, and phosphoinositide-binding mutants to quantify PI3P production, HOPS recruitment, and autophagosome-endolysosome fusion.

Hypothesis: RUBCNL requires separable STX17/UVRAG interaction surfaces and phosphoinositide binding to recruit PI3KC3/HOPS and promote autophagosome maturation.

Type: PACER adaptor separation-of-function rescue

Experiment: Endogenously tag RUBCNL, STX17, UVRAG, a PI3P reporter, and HOPS markers and follow recruitment timing during starvation and recovery.

Hypothesis: PACER occupancy marks STX17-positive autophagosomes that are competent for PI3KC3/HOPS recruitment and subsequent fusion with endolysosomal compartments.

Type: endogenous live-cell maturation imaging

📚 Additional Documentation

Notes

(RUBCNL-notes.md)

RUBCNL review notes

Scope

RUBCNL/PACER is reviewed in the PN class III PI3K complex 2/autophagosome maturation branch. PN entries without PMIDs were used as context only. The main curation question is whether RUBCNL should be represented only by autophagosome maturation/fusion process terms, or also by a more specific adaptor/PI3KC3-C2-associated complex context.

Evidence synthesis

RUBCNL is a positive late-autophagy regulator. The discovery abstract reports that Pacer "positively regulates autophagosome maturation", "stimulate[s] Vps34 kinase activity", and "recruits PI3KC3 and HOPS complexes" by "anchoring to the autophagosomal SNARE Stx17" [PMID:28306502, "positively regulates autophagosome maturation"; PMID:28306502, "stimulate Vps34 kinase activity"; PMID:28306502, "recruits PI3KC3 and HOPS complexes"; PMID:28306502, "anchoring to the autophagosomal SNARE Stx17"]. This supports autophagosome maturation, autophagosome-lysosome fusion, autophagosome-endosome fusion, and an adaptor/recruitment interpretation for the generic protein-binding annotations.

The mTORC1/GSK3-TIP60 paper supports regulation of the same late maturation role. Its abstract states that signaling pathways "modulate autophagosome maturation through Pacer", that mTORC1 phosphorylation can "disrupt the association of Pacer with Stx17 and the HOPS complex", and that TIP60-mediated acetylation "facilitates HOPS complex recruitment" and is "required for autophagosome maturation and lipid droplet clearance" [PMID:30704899, "modulate autophagosome maturation through Pacer"; PMID:30704899, "disrupt the association of Pacer with Stx17 and the HOPS complex"; PMID:30704899, "facilitates HOPS complex recruitment"; PMID:30704899, "required for autophagosome maturation and lipid droplet clearance"]. This supports retaining autophagosome maturation as core and treating lipid metabolic process regulation as non-core downstream physiology.

UniProt summarizes the same mechanism: RUBCNL "promotes autophagosome maturation", acts by "facilitating the biogenesis of phosphatidylinositol 3-phosphate", and "promotes the recruitment of PI3K/PI3KC3 and HOPS complexes" [file:human/RUBCNL/RUBCNL-uniprot.txt, "promotes autophagosome maturation"; file:human/RUBCNL/RUBCNL-uniprot.txt, "facilitating the biogenesis of phosphatidylinositol 3-phosphate"; file:human/RUBCNL/RUBCNL-uniprot.txt, "promotes the recruitment of PI3K/PI3KC3 and HOPS complexes"]. It also reports direct interaction with UVRAG and STX17 and autophagosome-membrane localization [file:human/RUBCNL/RUBCNL-uniprot.txt, "Interacts with UVRAG"; file:human/RUBCNL/RUBCNL-uniprot.txt, "Interacts with STX17"; file:human/RUBCNL/RUBCNL-uniprot.txt, "autophagosome membrane"].

The phosphoinositide-binding annotations are supported. UniProt says RUBCNL binds "phosphatidylinositol 3-phosphate", "phosphatidylinositol-4-phosphate", and "phosphatidylinositol-5-phosphate" [file:human/RUBCNL/RUBCNL-uniprot.txt, "phosphatidylinositol 3-phosphate"; file:human/RUBCNL/RUBCNL-uniprot.txt, "phosphatidylinositol-4-phosphate"; file:human/RUBCNL/RUBCNL-uniprot.txt, "phosphatidylinositol-5-phosphate"]. The generic inherited phosphatidylinositol phosphate binding row is true but less specific than the IDA-supported lipid-binding terms.

Generic protein binding rows are over-annotations. The useful molecular-function interpretation is protein-macromolecule adaptor activity or recruitment activity: RUBCNL links STX17-positive autophagosomes with UVRAG/PI3KC3 and HOPS machinery during late autophagosome maturation.

Falcon

Falcon deep research was run for RUBCNL on 2026-06-02 but timed out after 600 seconds, and no RUBCNL-deep-research-falcon.md report was produced. This review therefore uses the local GOA, UniProt, cached publication files, and the additional notes above.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: the prior wording framed RUBCNL in the Proteostasis Network context as an autophagosome-maturation adaptor/recruitment factor associated with PI3KC3-C2 and HOPS, not as generic protein binding.

Pn Notes

(RUBCNL-pn-notes.md)

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

AIGR review YAML: present - genes/human/RUBCNL/RUBCNL-ai-review.yaml
AIGR review HTML: present - genes/human/RUBCNL/RUBCNL-ai-review.html
Gene notes: present - genes/human/RUBCNL/RUBCNL-notes.md
GOA TSV: present - genes/human/RUBCNL/RUBCNL-goa.tsv
UniProt record: present - genes/human/RUBCNL/RUBCNL-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/RUBCNL.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/RUBCNL.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: 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.

📄 View Raw YAML

id: Q9H714
gene_symbol: RUBCNL
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
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.
alternative_products:
- name: '1'
  id: Q9H714-5
- name: '5'
  id: Q9H714-4
  sequence_note: VSP_014713
- name: '2'
  id: Q9H714-3
  sequence_note: VSP_014708
- name: '3'
  id: Q9H714-1
  sequence_note: VSP_014711, VSP_014712
- name: '4'
  id: Q9H714-2
  sequence_note: VSP_014709, VSP_014710
- name: '6'
  id: Q9H714-6
  sequence_note: VSP_055260
existing_annotations:
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Autophagosome membrane localization is supported and central to PACER late-autophagy function.
    action: ACCEPT
    reason: RUBCNL/PACER is recruited to late autophagic/autophagosome membranes and uses STX17-positive
      autophagosomes as the platform for PI3KC3 and HOPS recruitment.
    additional_reference_ids: &id001
    - PMID:28306502
    - PMID:30704899
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by: &id003
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Cytoplasmic vesicle, autophagosome membrane
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Associates with late autophagic structure
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Recruitment to autophagosome membrane is promoted by autophagic stimuli
    - reference_id: PMID:28306502
      supporting_text: Pacer localizes to autophagic structures
- term:
    id: GO:0061909
    label: autophagosome-lysosome fusion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Autophagosome-lysosome fusion is supported as a core late-autophagy process for RUBCNL.
    action: ACCEPT
    reason: PACER recruits PI3KC3 and HOPS complexes at STX17-positive autophagosomes, supporting fusion
      specificity with late endosomes/lysosomes.
    additional_reference_ids: *id001
    supported_by: &id002
    - reference_id: PMID:28306502
      supporting_text: recruits PI3KC3 and HOPS complexes
    - reference_id: PMID:28306502
      supporting_text: anchoring to the autophagosomal SNARE Stx17
    - reference_id: PMID:28306502
      supporting_text: HOPS complex mediates the fusion of intracellular vesicles to lysosome
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: regulate the fusion specificity of autophagosomes with late endosomes/lysosomes
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Interacts with STX17
- term:
    id: GO:0061910
    label: autophagosome-endosome fusion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Autophagosome-endosome fusion is supported as part of the same late maturation/fusion role.
    action: ACCEPT
    reason: The curated mechanism places RUBCNL at STX17-positive autophagosomes where it recruits PI3KC3 and
      HOPS machinery to regulate fusion with late endosomal/lysosomal compartments.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Autophagosome maturation is the central RUBCNL biological-process annotation.
    action: ACCEPT
    reason: Both functional papers and UniProt support PACER as a positive regulator of late autophagosome
      maturation through STX17, PI3KC3, HOPS, and regulated phosphorylation/acetylation.
    additional_reference_ids: *id001
    supported_by: &id006
    - reference_id: PMID:28306502
      supporting_text: positively regulates autophagosome maturation
    - reference_id: PMID:28306502
      supporting_text: stimulate Vps34 kinase activity
    - reference_id: PMID:28306502
      supporting_text: recruits PI3KC3 and HOPS complexes
    - reference_id: PMID:28306502
      supporting_text: anchoring to the autophagosomal SNARE Stx17
    - reference_id: PMID:30704899
      supporting_text: modulate autophagosome maturation through Pacer
    - reference_id: PMID:30704899
      supporting_text: facilitates HOPS complex recruitment
    - reference_id: PMID:30704899
      supporting_text: required for autophagosome maturation and lipid droplet clearance
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: promotes autophagosome maturation
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
- term:
    id: GO:1901981
    label: phosphatidylinositol phosphate binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: The broad phosphatidylinositol phosphate binding term is true but should be replaced by specific
      lipid-binding terms.
    action: MODIFY
    reason: RUBCNL has IDA-supported binding to PtdIns(3)P, PtdIns(4)P, and PtdIns(5)P, so the inherited
      generic term is less informative than the specific existing annotations.
    additional_reference_ids:
    - GO_REF:0000033
    - PMID:28306502
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by: &id005
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Binds phosphoinositides phosphatidylinositol 3-phosphate
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: GO:0032266; F:phosphatidylinositol-3-phosphate binding
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: GO:0070273; F:phosphatidylinositol-4-phosphate binding
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: GO:0010314; F:phosphatidylinositol-5-phosphate binding
    proposed_replacement_terms:
    - id: GO:0032266
      label: phosphatidylinositol-3-phosphate binding
    - id: GO:0070273
      label: phosphatidylinositol-4-phosphate binding
    - id: GO:0010314
      label: phosphatidylinositol-5-phosphate binding
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Autophagosome membrane localization is supported and central to PACER late-autophagy function.
    action: ACCEPT
    reason: RUBCNL/PACER is recruited to late autophagic/autophagosome membranes and uses STX17-positive
      autophagosomes as the platform for PI3KC3 and HOPS recruitment.
    additional_reference_ids: *id001
    supported_by: *id003
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: located_in
  review:
    summary: Autophagosome membrane localization is supported and central to PACER late-autophagy function.
    action: ACCEPT
    reason: RUBCNL/PACER is recruited to late autophagic/autophagosome membranes and uses STX17-positive
      autophagosomes as the platform for PI3KC3 and HOPS recruitment.
    additional_reference_ids: *id001
    supported_by: *id003
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28306502
  qualifier: enables
  review:
    summary: The interaction evidence is real, but generic protein binding obscures the PACER
      adaptor/recruitment function.
    action: MARK_AS_OVER_ANNOTATED
    reason: RUBCNL interaction data should be represented by the specific STX17/UVRAG-dependent adaptor role
      in PI3KC3/HOPS recruitment and autophagosome maturation, not by generic protein binding.
    additional_reference_ids: *id001
    supported_by: &id004
    - reference_id: PMID:28306502
      supporting_text: recruits PI3KC3 and HOPS complexes
    - reference_id: PMID:28306502
      supporting_text: anchoring to the autophagosomal SNARE Stx17
    - reference_id: PMID:30704899
      supporting_text: disrupt the association of Pacer with Stx17 and the HOPS complex
    - reference_id: PMID:30704899
      supporting_text: facilitates HOPS complex recruitment
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Interacts with UVRAG
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Interacts with STX17
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: association with the PI3K/PI3KC3 and HOPS complexes
    proposed_replacement_terms:
    - id: GO:0030674
      label: protein-macromolecule adaptor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30704899
  qualifier: enables
  review:
    summary: The interaction evidence is real, but generic protein binding obscures the PACER
      adaptor/recruitment function.
    action: MARK_AS_OVER_ANNOTATED
    reason: RUBCNL interaction data should be represented by the specific STX17/UVRAG-dependent adaptor role
      in PI3KC3/HOPS recruitment and autophagosome maturation, not by generic protein binding.
    additional_reference_ids: *id001
    supported_by: *id004
    proposed_replacement_terms:
    - id: GO:0030674
      label: protein-macromolecule adaptor activity
- term:
    id: GO:0010314
    label: phosphatidylinositol-5-phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: enables
  review:
    summary: phosphatidylinositol-5-phosphate binding is directly supported and contributes to
      autophagosome-membrane recruitment/function.
    action: ACCEPT
    reason: The discovery study and UniProt support phosphoinositide binding by PACER, including PtdIns(3)P,
      PtdIns(4)P, and PtdIns(5)P.
    additional_reference_ids:
    - PMID:28306502
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by: *id005
- term:
    id: GO:0019216
    label: regulation of lipid metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Regulation of lipid metabolic process is supported as downstream organismal physiology, not the
      core PN molecular role.
    action: KEEP_AS_NON_CORE
    reason: The direct human evidence centers on autophagosome maturation; lipid and glycogen homeostasis are
      described as additional or by-similarity biology downstream of PACER-dependent autophagy.
    additional_reference_ids:
    - GO_REF:0000024
    - PMID:30704899
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by:
    - reference_id: PMID:30704899
      supporting_text: required for autophagosome maturation and lipid droplet clearance
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: acts as a regulator of lipid and glycogen homeostasis
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Acetylated by KAT5/TIP60 under autophagy induction
- term:
    id: GO:0032266
    label: phosphatidylinositol-3-phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: enables
  review:
    summary: phosphatidylinositol-3-phosphate binding is directly supported and contributes to
      autophagosome-membrane recruitment/function.
    action: ACCEPT
    reason: The discovery study and UniProt support phosphoinositide binding by PACER, including PtdIns(3)P,
      PtdIns(4)P, and PtdIns(5)P.
    additional_reference_ids:
    - PMID:28306502
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by: *id005
- term:
    id: GO:0061909
    label: autophagosome-lysosome fusion
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: involved_in
  review:
    summary: Autophagosome-lysosome fusion is supported as a core late-autophagy process for RUBCNL.
    action: ACCEPT
    reason: PACER recruits PI3KC3 and HOPS complexes at STX17-positive autophagosomes, supporting fusion
      specificity with late endosomes/lysosomes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0061910
    label: autophagosome-endosome fusion
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: involved_in
  review:
    summary: Autophagosome-endosome fusion is supported as part of the same late maturation/fusion role.
    action: ACCEPT
    reason: The curated mechanism places RUBCNL at STX17-positive autophagosomes where it recruits PI3KC3 and
      HOPS machinery to regulate fusion with late endosomal/lysosomal compartments.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0070273
    label: phosphatidylinositol-4-phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: enables
  review:
    summary: phosphatidylinositol-4-phosphate binding is directly supported and contributes to
      autophagosome-membrane recruitment/function.
    action: ACCEPT
    reason: The discovery study and UniProt support phosphoinositide binding by PACER, including PtdIns(3)P,
      PtdIns(4)P, and PtdIns(5)P.
    additional_reference_ids:
    - PMID:28306502
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by: *id005
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IDA
  original_reference_id: PMID:28306502
  qualifier: involved_in
  review:
    summary: Autophagosome maturation is the central RUBCNL biological-process annotation.
    action: ACCEPT
    reason: Both functional papers and UniProt support PACER as a positive regulator of late autophagosome
      maturation through STX17, PI3KC3, HOPS, and regulated phosphorylation/acetylation.
    additional_reference_ids: *id001
    supported_by: *id006
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IDA
  original_reference_id: PMID:30704899
  qualifier: involved_in
  review:
    summary: Autophagosome maturation is the central RUBCNL biological-process annotation.
    action: ACCEPT
    reason: Both functional papers and UniProt support PACER as a positive regulator of late autophagosome
      maturation through STX17, PI3KC3, HOPS, and regulated phosphorylation/acetylation.
    additional_reference_ids: *id001
    supported_by: *id006
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IPI
  original_reference_id: PMID:28306502
  qualifier: enables
  review:
    summary: PACER has a supported adaptor/recruitment role at STX17-positive autophagosomes.
    action: NEW
    reason: Add this as a more informative molecular-function annotation than generic protein binding. RUBCNL
      links STX17-positive autophagosomes with UVRAG, PI3KC3, and HOPS machinery to drive autophagosome
      maturation.
    additional_reference_ids: *id001
    supported_by: *id004
- term:
    id: GO:0034272
    label: phosphatidylinositol 3-kinase complex, class III, type II
  evidence_type: IPI
  original_reference_id: PMID:28306502
  qualifier: part_of
  review:
    summary: RUBCNL should be added as a PI3KC3-C2-associated regulatory/adaptor context component.
    action: NEW
    reason: The PN projection highlights missing PI3KC3-C2 context, and the functional evidence shows
      PACER/UVRAG-dependent recruitment and activation of PI3KC3 at autophagosomes during late autophagy.
    additional_reference_ids:
    - PMID:28306502
    - file:human/RUBCNL/RUBCNL-uniprot.txt
    - file:human/RUBCNL/RUBCNL-notes.md
    supported_by:
    - reference_id: PMID:28306502
      supporting_text: recruits PI3KC3 and HOPS complexes
    - reference_id: PMID:28306502
      supporting_text: stimulate Vps34 kinase activity
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
    - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
      supporting_text: Interacts with UVRAG
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment
    of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:28306502
  title: Pacer Mediates the Function of Class III PI3K and HOPS Complexes in Autophagosome Maturation by
    Engaging Stx17.
  findings: []
- id: PMID:30704899
  title: Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Regulation of Autophagosome Maturation and
    Lipid Metabolism.
  findings: []
- id: file:human/RUBCNL/RUBCNL-uniprot.txt
  title: UniProtKB record for human RUBCNL
  findings: []
- id: file:human/RUBCNL/RUBCNL-notes.md
  title: RUBCNL review notes
  findings: []
core_functions:
- molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  description: PACER/RUBCNL acts as a STX17-anchored autophagosome adaptor that recruits UVRAG-associated
    PI3KC3-C2 and HOPS machinery, stimulates Vps34/PI3KC3-dependent PtdIns(3)P production, and promotes late
    autophagosome maturation and fusion with endolysosomal compartments.
  directly_involved_in:
  - id: GO:0097352
    label: autophagosome maturation
  - id: GO:0061909
    label: autophagosome-lysosome fusion
  - id: GO:0061910
    label: autophagosome-endosome fusion
  locations:
  - id: GO:0000421
    label: autophagosome membrane
  in_complex:
    id: GO:0034272
    label: phosphatidylinositol 3-kinase complex, class III, type II
  supported_by:
  - reference_id: PMID:28306502
    supporting_text: positively regulates autophagosome maturation
  - reference_id: PMID:28306502
    supporting_text: stimulate Vps34 kinase activity
  - reference_id: PMID:28306502
    supporting_text: recruits PI3KC3 and HOPS complexes
  - reference_id: PMID:28306502
    supporting_text: anchoring to the autophagosomal SNARE Stx17
  - reference_id: PMID:30704899
    supporting_text: facilitates HOPS complex recruitment
  - reference_id: PMID:30704899
    supporting_text: required for autophagosome maturation and lipid droplet clearance
  - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
    supporting_text: promotes the recruitment of PI3K/PI3KC3 and HOPS complexes
  - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
    supporting_text: Interacts with UVRAG
  - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
    supporting_text: Interacts with STX17
  - reference_id: file:human/RUBCNL/RUBCNL-uniprot.txt
    supporting_text: Cytoplasmic vesicle, autophagosome membrane
proposed_new_terms: []
suggested_questions:
- question: Should RUBCNL/PACER be curated as part_of GO:0034272 PI3KC3-C2, or represented as a PI3KC3/HOPS
    recruitment adaptor without complex membership?
  experts:
  - GO autophagy editors
  - ComplexPortal curators
- question: Should generic RUBCNL protein-binding annotations be replaced by protein-macromolecule adaptor
    activity for STX17/UVRAG/PI3KC3/HOPS recruitment?
  experts:
  - GO molecular function editors
  - GO autophagy editors
- question: Should regulation of lipid metabolic process remain a non-core by-similarity annotation, or should
    it be tied more explicitly to autophagy-dependent lipid droplet clearance?
  experts:
  - GO autophagy editors
  - GO lipid metabolism editors
suggested_experiments:
- experiment_type: PACER adaptor separation-of-function rescue
  hypothesis: RUBCNL requires separable STX17/UVRAG interaction surfaces and phosphoinositide binding to
    recruit PI3KC3/HOPS and promote autophagosome maturation.
  description: Use RUBCNL knockout/rescue cells with STX17-binding, UVRAG-binding, and
    phosphoinositide-binding mutants to quantify PI3P production, HOPS recruitment, and
    autophagosome-endolysosome fusion.
- experiment_type: endogenous live-cell maturation imaging
  hypothesis: PACER occupancy marks STX17-positive autophagosomes that are competent for PI3KC3/HOPS
    recruitment and subsequent fusion with endolysosomal compartments.
  description: Endogenously tag RUBCNL, STX17, UVRAG, a PI3P reporter, and HOPS markers and follow recruitment
    timing during starvation and recovery.

RUBCNL

Gene Description

Existing Annotations Review

Core Functions

PACER/RUBCNL acts as a STX17-anchored autophagosome adaptor that recruits UVRAG-associated PI3KC3-C2 and HOPS machinery, stimulates Vps34/PI3KC3-dependent PtdIns(3)P production, and promotes late autophagosome maturation and fusion with endolysosomal compartments.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

RUBCNL review notes

Scope

Evidence synthesis

Falcon

Description cleanup note

Pn Notes

RUBCNL PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Class 3 PI3K complex 2, direct | Class 3 PI3K complex 2 component

Projected GO annotations (1)

Note

📄 View Raw YAML