SH3GLB1 encodes endophilin B1/Bif-1, an N-BAR/SH3 membrane-curvature adaptor that links UVRAG/BECN1/PI3KC3-C2 autophagy signaling to ATG9-positive Golgi membrane fission and autophagosome assembly. Its core functions include PI3KC3 activation, adaptor-mediated association with UVRAG/Beclin 1, and membrane fission/tubulation at Golgi/autophagosome membranes. SH3GLB1 also has supported non-core roles in mitochondrial outer membrane dynamics, Bax/Bak-dependent apoptosis, receptor degradation, cytokinesis, and older lipid-binding/acyltransferase biochemistry.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006897 endocytosis | IBA GO_REF:0000033 | MODIFY | Summary: Endocytosis is directionally related but too broad for SH3GLB1. Reason: SH3GLB1/endophilin B1 contributes to membrane curvature, ATG9/Golgi fission, receptor degradation, and endocytic trafficking contexts; the broad endocytosis parent should be narrowed where possible. Proposed replacements: membrane fission receptor catabolic process Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:20643123 regulates both receptor degradation and cytokinesis |
| GO:0016020 membrane | IBA GO_REF:0000033 | MODIFY | Summary: Membrane is true but too broad for a peripheral N-BAR autophagy/mitochondrial membrane factor. Reason: Use the supported specific membrane locations: Golgi membrane, autophagosome membrane, and mitochondrial outer membrane, with the mitochondrial branch retained as non-core. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Golgi apparatus membrane file:human/SH3GLB1/SH3GLB1-uniprot.txt Mitochondrion outer membrane file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasmic vesicle, autophagosome |
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-macromolecule adaptor activity is a good core molecular-function description for Bif-1. Reason: SH3GLB1 uses BAR/SH3-mediated membrane and protein interactions to connect UVRAG/BECN1/PI3KC3-C2 with autophagy membrane remodeling. Supporting Evidence: PMID:17891140 interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene (UVRAG) PMID:20643123 specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG; UVRAG bridges the interaction to BECN1 file:human/SH3GLB1/SH3GLB1-uniprot.txt complex II (PI3KC3-C2) PMID:11604418 directly bind and evaginate lipid bilayers into narrow tubules file:human/SH3GLB1/SH3GLB1-uniprot.txt induce membrane curvature and bind curved membranes |
| GO:0061024 membrane organization | IBA GO_REF:0000033 | MODIFY | Summary: Membrane organization is supported but should be represented by the more specific fission/tubulation terms. Reason: Bif-1/endophilin B1 is an N-BAR membrane-curvature protein; the specific supported processes are membrane fission and positive regulation of membrane tubulation during ATG9/Golgi trafficking. Proposed replacements: membrane fission positive regulation of membrane tubulation Supporting Evidence: PMID:11604418 directly bind and evaginate lipid bilayers into narrow tubules file:human/SH3GLB1/SH3GLB1-uniprot.txt induce membrane curvature and bind curved membranes file:human/SH3GLB1/SH3GLB1-uniprot.txt N-BAR domain PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi membrane localization is core for Bif-1-mediated ATG9 trafficking. Reason: SH3GLB1 localizes to Golgi membranes and drives starvation-induced Atg9-positive Golgi membrane fission for autophagosome biogenesis. Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:0000421 autophagosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Autophagosome membrane localization is core for SH3GLB1/Bif-1 autophagy function. Reason: Bif-1 localizes to autophagosomes after nutrient deprivation and supports autophagosome formation through UVRAG/PI3KC3-C2. Supporting Evidence: PMID:17891140 localizes to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasmic vesicle, autophagosome PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1. Reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as broad context only. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasm {ECO:0000269|PubMed:15452144} |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrial outer membrane localization is supported but non-core for this PN review. Reason: SH3GLB1 has a real mitochondrial morphology/apoptosis branch, but the PN-relevant core is PI3KC3-C2/autophagosome assembly. Supporting Evidence: PMID:15452144 required for maintenance of mitochondrial morphology PMID:15452144 required for the regulation of the outer mitochondrial membrane dynamics file:human/SH3GLB1/SH3GLB1-uniprot.txt May be required for normal outer mitochondrial membrane dynamics |
| GO:0030496 midbody | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Midbody localization is supported for the PI3KC3-C2/BIF-1 cytokinesis branch but non-core. Reason: The cytokinesis/midbody role is real but separate from the autophagy/ATG9 membrane fission core. Supporting Evidence: PMID:20643123 regulates both receptor degradation and cytokinesis PMID:20643123 strong localisation of these proteins to the midbody |
| GO:0005515 protein binding | IPI PMID:17891140 Bif-1 interacts with Beclin 1 through UVRAG and regulates au... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| 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 an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:24056303 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| 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 an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| 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 an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| 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 an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0042802 identical protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MODIFY | Summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology. Reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the homodimerization term is more specific. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an SH3 domain file:human/SH3GLB1/SH3GLB1-uniprot.txt Homodimer, and heterodimer with SH3GLB2 PMID:19805544 Endo B1 oligomerization is induced by Bax |
| GO:0042802 identical protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | MODIFY | Summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology. Reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the homodimerization term is more specific. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an SH3 domain file:human/SH3GLB1/SH3GLB1-uniprot.txt Homodimer, and heterodimer with SH3GLB2 PMID:19805544 Endo B1 oligomerization is induced by Bax |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology. Reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the homodimerization term is more specific. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an SH3 domain file:human/SH3GLB1/SH3GLB1-uniprot.txt Homodimer, and heterodimer with SH3GLB2 PMID:19805544 Endo B1 oligomerization is induced by Bax |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology. Reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the homodimerization term is more specific. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an SH3 domain file:human/SH3GLB1/SH3GLB1-uniprot.txt Homodimer, and heterodimer with SH3GLB2 PMID:19805544 Endo B1 oligomerization is induced by Bax |
| GO:0005504 fatty acid binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fatty acid binding is supported as older endophilin B isoform biochemistry but is non-core. Reason: The evidence is tied to endophilin B1 lipid binding/acyltransferase properties and brain-specific splice variants, not the central PN autophagy role. Supporting Evidence: PMID:12456676 binds to palmitoyl-CoA PMID:12456676 exhibits lysophosphatidic acid acyl transferase activity PMID:12456676 brain-specific |
| GO:0010508 positive regulation of autophagy | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of autophagy is a core SH3GLB1/Bif-1 annotation. Reason: Bif-1 activates PI3KC3 through UVRAG/BECN1 context, localizes to autophagosomes, and loss of Bif-1 suppresses autophagosome formation. Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation file:human/SH3GLB1/SH3GLB1-uniprot.txt Activates lipid kinase activity of PIK3C3 file:human/SH3GLB1/SH3GLB1-uniprot.txt probably by associating with the PI3K complex II PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II |
| GO:0016020 membrane | IEA GO_REF:0000107 | MODIFY | Summary: Membrane is true but too broad for a peripheral N-BAR autophagy/mitochondrial membrane factor. Reason: Use the supported specific membrane locations: Golgi membrane, autophagosome membrane, and mitochondrial outer membrane, with the mitochondrial branch retained as non-core. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Golgi apparatus membrane file:human/SH3GLB1/SH3GLB1-uniprot.txt Mitochondrion outer membrane file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasmic vesicle, autophagosome |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MODIFY | Summary: Protein-containing complex is too generic for SH3GLB1 in the PI3KC3-C2 branch. Reason: Bif-1 associates with UVRAG/BECN1/PI3KC3-C2; the type II class III PI3K complex term is the appropriate PN-specific replacement. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type II Supporting Evidence: PMID:17891140 interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene (UVRAG) PMID:20643123 specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG; UVRAG bridges the interaction to BECN1 file:human/SH3GLB1/SH3GLB1-uniprot.txt complex II (PI3KC3-C2) |
| GO:0042171 lysophosphatidic acid acyltransferase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lysophosphatidic acid acyltransferase activity is supported for endophilin B1 isoform/family biochemistry but is non-core. Reason: This activity is not the central proteostasis/autophagy function and should not override the stronger Bif-1/PI3KC3-C2 membrane-fission evidence. Supporting Evidence: PMID:12456676 binds to palmitoyl-CoA PMID:12456676 exhibits lysophosphatidic acid acyl transferase activity PMID:12456676 brain-specific |
| GO:0048102 autophagic cell death | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Autophagic cell death overstates the supported Bif-1 autophagy/apoptosis evidence. Reason: The evidence supports positive regulation of autophagy/autophagosome assembly and a distinct Bax/Bak mitochondrial apoptosis branch; direct autophagic cell death is a less precise and potentially misleading term. Proposed replacements: positive regulation of autophagy positive regulation of autophagosome assembly Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation PMID:16227588 interacts with Bax PMID:16227588 important component of the mitochondrial pathway for apoptosis |
| GO:0141038 phosphatidylinositol 3-kinase activator activity | IEA GO_REF:0000107 | ACCEPT | Summary: PI3K activator activity is core for SH3GLB1/Bif-1. Reason: Bif-1 activates PI3KC3 via the UVRAG/Beclin1 PI3KC3-C2 context during autophagy. Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation file:human/SH3GLB1/SH3GLB1-uniprot.txt Activates lipid kinase activity of PIK3C3 file:human/SH3GLB1/SH3GLB1-uniprot.txt probably by associating with the PI3K complex II PMID:17891140 interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene (UVRAG) PMID:20643123 specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 |
| GO:1903778 protein localization to vacuolar membrane | IEA GO_REF:0000107 | MODIFY | Summary: Protein localization to vacuolar membrane should be humanized/narrowed to autophagosome membrane and autophagosome assembly. Reason: The human evidence is Atg9 trafficking from Golgi membranes toward autophagosome biogenesis, not a generic vacuolar membrane localization process. Proposed replacements: positive regulation of autophagosome assembly autophagosome membrane Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:2000786 positive regulation of autophagosome assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of autophagosome assembly is a core SH3GLB1 process. Reason: Bif-1/Endophilin B1 promotes Atg9-positive Golgi membrane fission and PI3KC3-C2-dependent autophagosome biogenesis. Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1. Reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as broad context only. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasm {ECO:0000269|PubMed:15452144} |
| GO:0000139 Golgi membrane | EXP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | ACCEPT | Summary: Golgi membrane localization is core for Bif-1-mediated ATG9 trafficking. Reason: SH3GLB1 localizes to Golgi membranes and drives starvation-induced Atg9-positive Golgi membrane fission for autophagosome biogenesis. Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:19074440 Endophilin B1/Bif-1 stimulates BAX activation independently ... | KEEP AS NON CORE | Summary: Positive regulation of protein-containing complex assembly is supported in Bax activation context but non-core. Reason: This row reflects Bif-1/Bax apoptotic membrane-permeabilization biology rather than the PN autophagy core. Supporting Evidence: PMID:19074440 stimulatory effect of Bif-1 on BAX-driven MOMP PMID:19074440 BAX conformational activation file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX |
| GO:0032991 protein-containing complex | IDA PMID:19805544 Bax activates endophilin B1 oligomerization and lipid membra... | MODIFY | Summary: Protein-containing complex is too generic for Bax-induced Endo B1 oligomerization. Reason: The cited evidence supports Endo B1 oligomerization/lipid vesiculation in apoptosis, not a stable named complex term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:19805544 Endo B1 oligomerization is induced by Bax PMID:19805544 massive vesiculation of liposomes |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: Cadherin binding is a high-throughput interaction over-annotation for SH3GLB1. Reason: The HDA interactome row does not define SH3GLB1 core function; no supporting SH3GLB1 cadherin mechanism is evident from the curated functional record. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Endophilin-B1 |
| GO:0031647 regulation of protein stability | HMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | MARK AS OVER ANNOTATED | Summary: Regulation of protein stability from a high-throughput mitophagy screen is not a core SH3GLB1 function. Reason: The main text describes a genome-wide resource and mechanistic follow-up of other genes; SH3GLB1-specific functional support is better captured by mitochondrial membrane dynamics and autophagy membrane fission. Supporting Evidence: PMID:24270810 genome-wide small interfering RNA (siRNA) screens PMID:15452144 required for maintenance of mitochondrial morphology |
| GO:1903749 positive regulation of protein localization to mitochondrion | HMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | MARK AS OVER ANNOTATED | Summary: Positive regulation of protein localization to mitochondrion is a high-throughput mitophagy-screen overextension. Reason: SH3GLB1 has supported mitochondrial outer membrane dynamics, but this HMP process term is not the best representation of its function. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:24270810 parkin translocation to damaged mitochondria PMID:15452144 required for the regulation of the outer mitochondrial membrane dynamics |
| GO:0005737 cytoplasm | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1. Reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as broad context only. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasm {ECO:0000269|PubMed:15452144} |
| GO:0016241 regulation of macroautophagy | TAS PMID:21499257 Cdk5-mediated phosphorylation of endophilin B1 is required f... | ACCEPT | Summary: Regulation of macroautophagy is supported and core but less specific than the PI3KC3-C2/ATG9 mechanism. Reason: Cdk5 phosphorylation and Bif-1/PI3KC3-C2 studies support induced autophagy; the detailed mechanism is positive regulation of autophagosome assembly. Supporting Evidence: PMID:21499257 required for induced autophagy file:human/SH3GLB1/SH3GLB1-uniprot.txt required for autophagy induction in starved neurons PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation |
| GO:0034198 cellular response to amino acid starvation | IMP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | KEEP AS NON CORE | Summary: Amino-acid starvation response is the experimental context for Bif-1 autophagy induction and is non-core. Reason: The functional annotation should emphasize ATG9 trafficking/autophagosome assembly rather than the starvation stimulus itself. Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes |
| GO:0042149 cellular response to glucose starvation | IMP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | KEEP AS NON CORE | Summary: Glucose starvation response is an experimental context for Bif-1 autophagy induction and is non-core. Reason: The core process is starvation-induced ATG9/Golgi membrane fission and autophagosome assembly, not glucose starvation response per se. Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes |
| GO:0090148 membrane fission | IMP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | ACCEPT | Summary: Membrane fission is a core Bif-1/endophilin B1 process in ATG9 trafficking. Reason: Bif-1 N-BAR-dependent Golgi membrane fission supplies Atg9-positive membranes for autophagosome formation. Supporting Evidence: PMID:11604418 directly bind and evaginate lipid bilayers into narrow tubules file:human/SH3GLB1/SH3GLB1-uniprot.txt induce membrane curvature and bind curved membranes file:human/SH3GLB1/SH3GLB1-uniprot.txt N-BAR domain PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:1903527 positive regulation of membrane tubulation | IMP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | ACCEPT | Summary: Positive regulation of membrane tubulation is core for the N-BAR domain-mediated autophagy membrane source role. Reason: The N-BAR domain drives membrane binding/tubulation, and Bif-1-dependent Golgi tubulation/fragmentation supports ATG9 trafficking during autophagy. Supporting Evidence: PMID:11604418 directly bind and evaginate lipid bilayers into narrow tubules file:human/SH3GLB1/SH3GLB1-uniprot.txt induce membrane curvature and bind curved membranes file:human/SH3GLB1/SH3GLB1-uniprot.txt N-BAR domain PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II |
| GO:1903778 protein localization to vacuolar membrane | IMP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | MODIFY | Summary: Protein localization to vacuolar membrane should be humanized/narrowed to autophagosome membrane and autophagosome assembly. Reason: The human evidence is Atg9 trafficking from Golgi membranes toward autophagosome biogenesis, not a generic vacuolar membrane localization process. Proposed replacements: positive regulation of autophagosome assembly autophagosome membrane Supporting Evidence: PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:2000786 positive regulation of autophagosome assembly | IMP PMID:21068542 Bif-1 regulates Atg9 trafficking by mediating the fission of... | ACCEPT | Summary: Positive regulation of autophagosome assembly is a core SH3GLB1 process. Reason: Bif-1/Endophilin B1 promotes Atg9-positive Golgi membrane fission and PI3KC3-C2-dependent autophagosome biogenesis. Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II PMID:21068542 the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt regulate the trafficking of ATG9A from the Golgi complex |
| GO:0000421 autophagosome membrane | IDA PMID:17891140 Bif-1 interacts with Beclin 1 through UVRAG and regulates au... | ACCEPT | Summary: Autophagosome membrane localization is core for SH3GLB1/Bif-1 autophagy function. Reason: Bif-1 localizes to autophagosomes after nutrient deprivation and supports autophagosome formation through UVRAG/PI3KC3-C2. Supporting Evidence: PMID:17891140 localizes to autophagosomes file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasmic vesicle, autophagosome PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation |
| GO:0010508 positive regulation of autophagy | IMP PMID:17891140 Bif-1 interacts with Beclin 1 through UVRAG and regulates au... | ACCEPT | Summary: Positive regulation of autophagy is a core SH3GLB1/Bif-1 annotation. Reason: Bif-1 activates PI3KC3 through UVRAG/BECN1 context, localizes to autophagosomes, and loss of Bif-1 suppresses autophagosome formation. Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation file:human/SH3GLB1/SH3GLB1-uniprot.txt Activates lipid kinase activity of PIK3C3 file:human/SH3GLB1/SH3GLB1-uniprot.txt probably by associating with the PI3K complex II PMID:21068542 tubulation and fragmentation of Atg9-positive Golgi membranes PMID:21068542 Bif-1/Endophilin B1 and the PI3KC3 complex II |
| GO:0030496 midbody | IDA PMID:20643123 A phosphatidylinositol 3-kinase class III sub-complex contai... | KEEP AS NON CORE | Summary: Midbody localization is supported for the PI3KC3-C2/BIF-1 cytokinesis branch but non-core. Reason: The cytokinesis/midbody role is real but separate from the autophagy/ATG9 membrane fission core. Supporting Evidence: PMID:20643123 regulates both receptor degradation and cytokinesis PMID:20643123 strong localisation of these proteins to the midbody |
| GO:0032465 regulation of cytokinesis | IMP PMID:20643123 A phosphatidylinositol 3-kinase class III sub-complex contai... | KEEP AS NON CORE | Summary: Regulation of cytokinesis is supported but non-core. Reason: A PI3KC3-C2/BIF-1-containing subcomplex regulates cytokinesis and receptor degradation, but this is outside the main autophagy membrane fission role. Supporting Evidence: PMID:20643123 regulates both receptor degradation and cytokinesis PMID:20643123 strong localisation of these proteins to the midbody |
| GO:0032801 receptor catabolic process | IMP PMID:20643123 A phosphatidylinositol 3-kinase class III sub-complex contai... | KEEP AS NON CORE | Summary: Receptor catabolic process is supported but non-core. Reason: BIF-1-containing PI3KC3-C2 contributes to degradative endocytic traffic, but the PN core is autophagy/ATG9 membrane fission. Supporting Evidence: PMID:20643123 regulates both receptor degradation and cytokinesis PMID:20643123 growth factor receptor degradation |
| GO:0048102 autophagic cell death | IMP PMID:17891140 Bif-1 interacts with Beclin 1 through UVRAG and regulates au... | MARK AS OVER ANNOTATED | Summary: Autophagic cell death overstates the supported Bif-1 autophagy/apoptosis evidence. Reason: The evidence supports positive regulation of autophagy/autophagosome assembly and a distinct Bax/Bak mitochondrial apoptosis branch; direct autophagic cell death is a less precise and potentially misleading term. Proposed replacements: positive regulation of autophagy positive regulation of autophagosome assembly Supporting Evidence: PMID:17891140 functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3) PMID:17891140 loss of Bif-1 suppresses autophagosome formation PMID:16227588 interacts with Bax PMID:16227588 important component of the mitochondrial pathway for apoptosis |
| GO:0005515 protein binding | IPI PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1 function. Reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association, homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds BAX file:human/SH3GLB1/SH3GLB1-uniprot.txt Interacts with UVRAG file:human/SH3GLB1/SH3GLB1-uniprot.txt Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 |
| GO:0005737 cytoplasm | IDA PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an... | KEEP AS NON CORE | Summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1. Reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as broad context only. Supporting Evidence: file:human/SH3GLB1/SH3GLB1-uniprot.txt Cytoplasm {ECO:0000269|PubMed:15452144} |
| GO:0042803 protein homodimerization activity | IPI PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an... | ACCEPT | Summary: Protein homodimerization is supported and relevant to endophilin BAR-domain membrane remodeling. Reason: SH3GLB1 homodimer/oligomer formation is part of the endophilin membrane-curvature mechanism and is more specific than identical protein binding. Supporting Evidence: PMID:11161816 SH3GLB, a new endophilin-related protein family featuring an SH3 domain file:human/SH3GLB1/SH3GLB1-uniprot.txt Homodimer, and heterodimer with SH3GLB2 PMID:19805544 Endo B1 oligomerization is induced by Bax |
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Download this section (compressed HTML)Q: Should SH3GLB1 be directly curated to GO:0034272 class III PI3K complex type II, or only to PI3KC3 activator/adaptor activity with PI3KC3-C2 context?
Suggested experts: GO autophagy editors, ComplexPortal curators, Reactome autophagy curators
Q: Is membrane fission or positive regulation of membrane tubulation the best GO process for Bif-1-mediated Atg9-positive Golgi membrane remodeling during autophagosome assembly?
Suggested experts: GO autophagy editors, membrane trafficking experts
Q: Should autophagic cell death annotations for Bif-1 be replaced by positive regulation of autophagy plus separate Bax/Bak mitochondrial apoptosis annotations?
Suggested experts: GO apoptosis editors, GO autophagy editors
Experiment: Rescue SH3GLB1 knockout cells with N-BAR, SH3, and dimerization mutants and measure PI3KC3 activity, Atg9 redistribution, Golgi membrane fission, and LC3/WIPI autophagosome assembly.
Hypothesis: Bif-1 requires both N-BAR membrane remodeling and SH3-dependent UVRAG/PI3KC3-C2 engagement to support Atg9 trafficking and autophagosome assembly.
Type: Bif-1 autophagy membrane-fission rescue assay
Experiment: Compare wild type and Bax-binding/mitochondrial-targeting SH3GLB1 mutants for mitochondrial morphology, Bax/Bak activation, and autophagic flux in the same background.
Hypothesis: SH3GLB1 mitochondrial apoptosis and PI3KC3-C2 autophagy roles are genetically separable.
Type: separation-of-function apoptosis versus autophagy assay
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