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.
| 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 |
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Download this section (compressed HTML)Q: Should RUBCNL/PACER be curated as part_of GO:0034272 PI3KC3-C2, or represented as a PI3KC3/HOPS recruitment adaptor without complex membership?
Suggested experts: GO autophagy editors, ComplexPortal curators
Q: Should generic RUBCNL protein-binding annotations be replaced by protein-macromolecule adaptor activity for STX17/UVRAG/PI3KC3/HOPS recruitment?
Suggested experts: GO molecular function editors, GO autophagy editors
Q: 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?
Suggested experts: GO autophagy editors, GO lipid metabolism editors
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
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