RUBCN encodes Rubicon, a RUN/RH-domain regulator that associates with the UVRAG-containing class III PI3K complex II and Rab7 to inhibit PIK3C3/VPS34 activity, endosome maturation, and autophagosome maturation. RUBCN is a negative PI3KC3-C2/autophagosome maturation regulator rather than an autophagy activator. It localizes mainly to late endosome/lysosome and early endosome compartments and also has non-core pathogen/innate-immune interaction biology described in UniProt.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: early endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0005770 late endosome | IBA GO_REF:0000033 | ACCEPT | Summary: late endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0045806 negative regulation of endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of endocytosis/endocytic trafficking is a core Rubicon function. Reason: Rubicon inhibits endosome maturation and endocytic pathway progression through Rab7 and UVRAG/PI3KC3-C2 interactions. Supporting Evidence: PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS PMID:20943950 specifically and directly interact with Rab7 via their RH domain PMID:20943950 simultaneously binding both Rab7 and PI3-kinase PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes |
| GO:1901097 negative regulation of autophagosome maturation | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of autophagosome maturation is the central RUBCN autophagy annotation. Reason: Rubicon inhibits UVRAG-containing PI3KC3-C2 and autophagosome maturation; knockdown enhances autophagy at the maturation step. Supporting Evidence: PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes PMID:19270696 Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step PMID:21062745 negative regulator of PI3KC3 and autophagosome maturation file:human/RUBCN/RUBCN-uniprot.txt negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy PMID:21062745 interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain PMID:21062745 inhibition of PI3KC3 lipid kinase activity by Rubicon file:human/RUBCN/RUBCN-uniprot.txt Inhibits PIK3C3 activity |
| GO:1901981 phosphatidylinositol phosphate binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phosphatidylinositol phosphate binding is plausible but not the primary experimentally supported Rubicon function. Reason: The local human evidence emphasizes PI3KC3/Rab7/UVRAG interaction and PI3KC3 inhibition rather than direct lipid binding; retain this inherited annotation as non-core pending stronger direct support. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: Lysosome localization is supported and relevant to late endosome/autophagosome maturation. Reason: Rubicon is predominantly in late endosome/lysosome compartments and regulates delivery/fusion steps toward lysosomes. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Lysosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: early endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0005770 late endosome | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:22493499 Receptor signaling lymphocyte-activation molecule family 1 (... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:24034250 EGFR-mediated Beclin 1 phosphorylation in autophagy suppress... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:25594178 A kinase-independent role for EGF receptor in autophagy init... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:34386498 ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005764 lysosome | EXP PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Lysosome localization is supported and relevant to late endosome/autophagosome maturation. Reason: Rubicon is predominantly in late endosome/lysosome compartments and regulates delivery/fusion steps toward lysosomes. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Lysosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG |
| GO:0005769 early endosome | EXP PMID:20974968 Rubicon controls endosome maturation as a Rab7 effector. | ACCEPT | Summary: early endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | MODIFY | Summary: The PI3K/AKT pathway wording is misleading for Rubicon hVps34 inhibition. Reason: The cited evidence supports inhibition of class III PI3K/VPS34 lipid kinase activity and autophagosome maturation, not a general PI3K/AKT signaling pathway role. Proposed replacements: phosphatidylinositol 3-kinase inhibitor activity negative regulation of autophagosome maturation Supporting Evidence: PMID:21062745 interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain PMID:21062745 inhibition of PI3KC3 lipid kinase activity by Rubicon file:human/RUBCN/RUBCN-uniprot.txt Inhibits PIK3C3 activity PMID:21062745 negative regulator of PI3KC3 and autophagosome maturation file:human/RUBCN/RUBCN-uniprot.txt negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy |
| GO:0141039 phosphatidylinositol 3-kinase inhibitor activity | IDA PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | ACCEPT | Summary: PI3K inhibitor activity is the best molecular-function annotation for Rubicon. Reason: Rubicon inhibits PIK3C3/VPS34 lipid kinase activity through RUN-domain-dependent interaction with hVps34. Supporting Evidence: PMID:21062745 interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain PMID:21062745 inhibition of PI3KC3 lipid kinase activity by Rubicon file:human/RUBCN/RUBCN-uniprot.txt Inhibits PIK3C3 activity |
| GO:1901097 negative regulation of autophagosome maturation | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: Negative regulation of autophagosome maturation is the central RUBCN autophagy annotation. Reason: Rubicon inhibits UVRAG-containing PI3KC3-C2 and autophagosome maturation; knockdown enhances autophagy at the maturation step. Supporting Evidence: PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes PMID:19270696 Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step PMID:21062745 negative regulator of PI3KC3 and autophagosome maturation file:human/RUBCN/RUBCN-uniprot.txt negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy PMID:21062745 interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain PMID:21062745 inhibition of PI3KC3 lipid kinase activity by Rubicon file:human/RUBCN/RUBCN-uniprot.txt Inhibits PIK3C3 activity |
| GO:0071985 multivesicular body sorting pathway | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | KEEP AS NON CORE | Summary: Multivesicular body sorting is supported as endosomal trafficking context but is not the core PN autophagy term. Reason: Rubicon negatively regulates endocytic pathway progression and endosome maturation; retain this as a non-core endosomal trafficking branch. Supporting Evidence: PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS PMID:20943950 specifically and directly interact with Rab7 via their RH domain PMID:20943950 simultaneously binding both Rab7 and PI3-kinase |
| GO:1901097 negative regulation of autophagosome maturation | IMP PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | ACCEPT | Summary: Negative regulation of autophagosome maturation is the central RUBCN autophagy annotation. Reason: Rubicon inhibits UVRAG-containing PI3KC3-C2 and autophagosome maturation; knockdown enhances autophagy at the maturation step. Supporting Evidence: PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes PMID:19270696 Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step PMID:21062745 negative regulator of PI3KC3 and autophagosome maturation file:human/RUBCN/RUBCN-uniprot.txt negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy PMID:21062745 interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain PMID:21062745 inhibition of PI3KC3 lipid kinase activity by Rubicon file:human/RUBCN/RUBCN-uniprot.txt Inhibits PIK3C3 activity |
| GO:0005515 protein binding | IPI PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for RUBCN function. Reason: Replace protein binding with specific PI3KC3 inhibitor activity, PI3KC3-C2 association, Rab7/UVRAG regulatory context, and negative autophagosome/endosome maturation terms. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt interacts directly with PI3KC3 and UVRAG file:human/RUBCN/RUBCN-uniprot.txt Interacts with Rab7 file:human/RUBCN/RUBCN-uniprot.txt Rab7 and UVRAG compete for RUBCN binding |
| GO:0005769 early endosome | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: early endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0005770 late endosome | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: late endosome localization is supported for Rubicon endosome maturation biology. Reason: RUBCN is an endosomal/lysosomal Rab7 and UVRAG/PI3KC3-C2 regulator; early/late endosome localization fits the core negative endosome/autophagosome maturation role. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt Predominantly located in late endosomes/lysosomes file:human/RUBCN/RUBCN-uniprot.txt Late endosome {ECO:0000269|PubMed:19270696} file:human/RUBCN/RUBCN-uniprot.txt Early endosome PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS |
| GO:0005794 Golgi apparatus | IDA NOT PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: The negated Golgi colocalization annotation is supported by curated localization evidence. Reason: This is a NOT annotation. Primary Rubicon localization is endosome/lysosome, and UniProt explicitly notes that Rubicon is not detected in the Golgi apparatus. Supporting Evidence: file:human/RUBCN/RUBCN-uniprot.txt not at all in the Golgi apparatus PMID:19270696 GFP-Rubicon was localized at the endosome/lysosome |
| GO:0010507 negative regulation of autophagy | IMP PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Negative regulation of autophagy is supported and core, though less specific than autophagosome maturation. Reason: Rubicon knockdown enhances autophagy and maturation; the specific mechanism is PI3KC3-C2 inhibition and impaired autophagosome maturation. Supporting Evidence: PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes PMID:19270696 Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step PMID:21062745 negative regulator of PI3KC3 and autophagosome maturation file:human/RUBCN/RUBCN-uniprot.txt negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy PMID:21062745 interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain PMID:21062745 inhibition of PI3KC3 lipid kinase activity by Rubicon file:human/RUBCN/RUBCN-uniprot.txt Inhibits PIK3C3 activity |
| GO:0045806 negative regulation of endocytosis | IMP PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Negative regulation of endocytosis/endocytic trafficking is a core Rubicon function. Reason: Rubicon inhibits endosome maturation and endocytic pathway progression through Rab7 and UVRAG/PI3KC3-C2 interactions. Supporting Evidence: PMID:20974968 prevents endosome maturation through differential interactions with Rab7 and UVRAG PMID:20974968 sequesters UVRAG from C-VPS/HOPS PMID:20943950 specifically and directly interact with Rab7 via their RH domain PMID:20943950 simultaneously binding both Rab7 and PI3-kinase PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes |
| GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II | IPI PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | NEW | Summary: Rubicon should be added as a PI3KC3-C2-associated regulatory subunit/context component. Reason: RUBCN associates with the UVRAG-containing class III PI3K complex II and directly interacts with PIK3C3 and UVRAG; this is the specific complex context missing from GOA. Supporting Evidence: PMID:19270696 Rubicon binds only to a subpopulation of UVRAG complexes file:human/RUBCN/RUBCN-uniprot.txt Associates with PI3K (PI3KC3/PI3K-III/class III file:human/RUBCN/RUBCN-uniprot.txt complex II (PI3KC3-C2) |
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Download this section (compressed HTML)Q: Should RUBCN be curated as part_of GO:0034272 PI3KC3-C2, or represented only by PI3K inhibitor activity and UVRAG/Rab7 interaction context?
Suggested experts: GO autophagy editors, ComplexPortal curators
Q: Should negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction be replaced in GOA by phosphatidylinositol 3-kinase inhibitor activity for RUBCN?
Suggested experts: GO molecular function editors, GO signaling editors
Q: Should the Golgi colocalization annotation be removed given curated endosome/lysosome localization and explicit UniProt note that Rubicon is not detected at Golgi?
Suggested experts: GO cellular component editors, UniProt curators
Experiment: Use RUBCN knockout/rescue with RUN-domain hVps34-binding mutants and RH-domain Rab7-binding mutants to measure PI3KC3 lipid kinase activity, Rab7 activation, EGFR/endosome maturation, and autophagosome-lysosome fusion.
Hypothesis: RUBCN requires both PI3KC3-C2 and Rab7/UVRAG interaction surfaces to inhibit autophagosome and endosome maturation.
Type: Rubicon PI3KC3-C2/Rab7 separation-of-function rescue
Experiment: Perform live-cell imaging of tagged endogenous RUBCN, UVRAG, Rab7, and HOPS markers during starvation and endocytic cargo maturation to test whether RUBCN leaves endosomal/autophagosomal sites before fusion competence.
Hypothesis: RUBCN occupancy marks inhibited PI3KC3-C2/Rab7 compartments and must be relieved for maturation/fusion progression.
Type: endogenous live-cell maturation imaging
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