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. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002915557 · PANTHER internal tree node SUPPORTS TRANSFER Eukaryota-level PAINT node seeded only by human RUBCNL (IDA phosphoinositide binding). The transfer back to RUBCNL is sound; the issue is only that the generic parent is less informative than RUBCNL's own specific PtdIns(3)P/(4)P/(5)P binding 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... | MODIFY | Summary: IPI with STX17 (P56962). The PACER-STX17 interaction is real and functionally central, but generic protein binding obscures the adaptor role. Reason: PACER anchors to the autophagosomal SNARE STX17 and uses this anchorage to recruit UVRAG-PI3KC3 and HOPS complexes. The informative molecular function is protein-macromolecule adaptor activity (STX17-anchored recruitment of PI3KC3 and HOPS); syntaxin binding is a literal but less informative alternative. Generic protein binding is replaced, not retained. Proposed replacements: protein-macromolecule adaptor activity syntaxin binding 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... | REMOVE | Summary: IPI with MTOR (P42345). PACER is an mTORC1 substrate; the interaction reflects enzyme-substrate binding, not a PACER molecular function. Reason: The cited study shows mTORC1 phosphorylates PACER at Ser157 to switch off its function. Binding by the kinase describes MTOR's activity on PACER as a substrate, so no informative PACER molecular function can replace protein binding. Removal does not mean the interaction is false; it is captured by MTOR's kinase annotation and by PACER's regulation, not by a PACER binding term. Supporting Evidence: PMID:30704899 mTORC1 phosphorylates Pacer at serine157 to disrupt the association of Pacer with Stx17 and the HOPS complex file:human/RUBCNL/RUBCNL-uniprot.txt Phosphorylated by MTOR at Ser-157 under nutrient-rich conditions |
| 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 |
| GO:0005515 protein binding | IPI PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl... | MODIFY | Summary: IPI with UVRAG (Q9P2Y5). PACER binds UVRAG directly, and this interaction is the route by which PACER brings the UVRAG-containing PI3KC3 complex to autophagosomes. Reason: The direct PACER-UVRAG interaction (the protein is named Protein Associated with UVRAG as autophagy Enhancer) promotes association with PI3KC3 and HOPS complexes. Combined with STX17 anchorage, this is adaptor activity that links the autophagosomal SNARE to the PI3KC3-C2 and HOPS machinery. Replace generic protein binding with protein-macromolecule adaptor activity. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with UVRAG; the interaction is direct and promotes association with the PI3K/PI3KC3 and HOPS complexes PMID:28306502 Pacer recruits PI3KC3 and HOPS complexes to the autophagosome for their site-specific activation by anchoring to the autophagosomal SNARE Stx17 |
| GO:0005515 protein binding | IPI PMID:30704899 Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Re... | MODIFY | Summary: IPI with STX17 (P56962) from the mTORC1/TIP60 study. Same STX17 anchorage reported in the discovery paper; generic protein binding is uninformative. Reason: This study shows that the PACER-STX17 association is the regulated step, disrupted by mTORC1 phosphorylation. The interaction anchors PACER to autophagosomes for HOPS recruitment, so the informative function is protein-macromolecule adaptor activity (with syntaxin binding as the literal alternative). Proposed replacements: protein-macromolecule adaptor activity syntaxin binding Supporting Evidence: PMID:30704899 disrupt the association of Pacer with Stx17 and the HOPS complex file:human/RUBCNL/RUBCNL-uniprot.txt Interacts with STX17 (PubMed:28306502, PubMed:30704899) |
| GO:0005515 protein binding | IPI PMID:30704899 Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Re... | REMOVE | Summary: IPI with KAT5/TIP60 (Q92993). PACER is a KAT5 substrate; the interaction reflects enzyme-substrate binding, not a PACER molecular function. Reason: TIP60/KAT5 acetylates PACER under nutrient deprivation, which enhances HOPS recruitment. The binding describes KAT5 acting on PACER; there is no more informative PACER molecular function to substitute. Removal does not mean the interaction is false; the regulation is captured on KAT5 and in PACER's PTM biology. Supporting Evidence: PMID:30704899 promotes TIP60-mediated Pacer acetylation, which facilitates HOPS complex recruitment file:human/RUBCNL/RUBCNL-uniprot.txt Acetylated by KAT5/TIP60 under autophagy induction |
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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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