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
|
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
SH3GLB1/BIF-1/endophilin B1 is reviewed in the PN class III PI3K complex 2/autophagosome maturation neighborhood. PN entries without PMIDs were used as context only. The main curation question is how to represent a membrane-curvature BAR/SH3 adaptor that associates with UVRAG/PI3KC3-C2 but is also involved in mitochondrial morphology and Bax-dependent apoptosis.
The core PN-relevant evidence supports SH3GLB1 as a Bif-1/endophilin B1 adaptor for UVRAG/Beclin1/PI3KC3-C2 autophagy. The main autophagy paper reports that Bif-1 "interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene (UVRAG)" and "functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)" [PMID:17891140, "interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene (UVRAG)"; PMID:17891140, "functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)"]. It also states that Bif-1 localizes to autophagosomes after nutrient deprivation and that "loss of Bif-1 suppresses autophagosome formation" [PMID:17891140, "localizes to autophagosomes"; PMID:17891140, "loss of Bif-1 suppresses autophagosome formation"]. UniProt summarizes the same mechanism: SH3GLB1 "Activates lipid kinase activity of PIK3C3" and does so "probably by associating with the PI3K complex II (PI3KC3-C2)" [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"].
The ATG9/Golgi fission paper provides the strongest process-level support for membrane fission/tubulation during autophagosome assembly. It reports that nutrient starvation induces "tubulation and fragmentation of Atg9-positive Golgi membranes" and that this is dependent on "Bif-1/Endophilin B1 and the PI3KC3 complex II" [PMID:21068542, "tubulation and fragmentation of Atg9-positive Golgi membranes"; PMID:21068542, "Bif-1/Endophilin B1 and the PI3KC3 complex II"]. The authors state that Bif-1 regulates "the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes" [PMID:21068542, "the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to autophagosomes"]. This supports membrane fission, positive regulation of membrane tubulation, protein localization to vacuolar/autophagosome membrane after humanization, and positive regulation of autophagosome assembly.
The molecular-function basis is the endophilin N-BAR/SH3 architecture. A membrane-curvature paper reports that purified endophilin can "directly bind and evaginate lipid bilayers into narrow tubules" [PMID:11604418, "directly bind and evaginate lipid bilayers into narrow tubules"]. UniProt states that the N-BAR domain "induce membrane curvature and bind curved membranes" and that the SH3 domain is required for UVRAG interaction [file:human/SH3GLB1/SH3GLB1-uniprot.txt, "induce membrane curvature and bind curved membranes"; file:human/SH3GLB1/SH3GLB1-uniprot.txt, "The SH3 domain is required and sufficient for the interaction with UVRAG"].
A second, real but non-core branch concerns mitochondrial morphology and apoptosis. Endophilin B1 is reported as "required for maintenance of mitochondrial morphology" and specifically "required for the regulation of the outer mitochondrial membrane dynamics" [PMID:15452144, "required for maintenance of mitochondrial morphology"; PMID:15452144, "required for the regulation of the outer mitochondrial membrane dynamics"]. Bif-1 also "interacts with Bax" and is an "important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator" [PMID:16227588, "interacts with Bax"; PMID:16227588, "important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator"]. These rows should be retained as non-core or separated from the autophagy/PI3KC3-C2 function.
The older lysophosphatidic acid acyltransferase claim is isoform/endophilin-family context rather than the main PN function. The B1b paper states that endophilin B1 "binds to palmitoyl-CoA" and "exhibits lysophosphatidic acid acyl transferase activity", but also frames B1b/B1c as brain-specific splice variants [PMID:12456676, "binds to palmitoyl-CoA"; PMID:12456676, "exhibits lysophosphatidic acid acyl transferase activity"; PMID:12456676, "brain-specific"]. This should be kept non-core rather than treated as the central function of SH3GLB1 in proteostasis.
GO:0032991 protein-containing complex) toward GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II where supported by UVRAG/BECN1/PI3KC3-C2 evidence.GO:0005515 protein binding and most identical protein binding rows are over-annotated; use specific adaptor, homodimerization, UVRAG/PI3KC3-C2, and membrane-curvature terms instead.autophagic cell death cautiously. The Bif-1 papers link starvation survival/apoptosis and autophagy, but the supported autophagy process is better captured as positive regulation of autophagy/autophagosome assembly rather than direct annotation to autophagic cell death.Falcon deep research was started for SH3GLB1 on 2026-06-02. The run timed out after the configured 600 seconds and did not produce SH3GLB1-deep-research-falcon.md; the review therefore relies on local UniProt, GOA, and cached publication evidence.
The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.
*-deep-research*.md file found in this gene directory.more_specific_than_existing_goa. Review handles this via MODIFY of GO:0032991 β proposed_replacement GO:0034272 (rather than a standalone NEW row). GO:0034272 verified real. Review also adds membrane-fission (GO:0090148) and positive regulation of membrane tubulation (GO:1903527) as core β both verified real, non-obsolete, and beyond the PN story. Verdict: ADD/refine to GO:0034272 (review does via MODIFY) β aligned with PN.ALP|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Class 3 PI3K complex 2 component ; PN-node mapping: type leaf mapped, ok_for_propagation_to_go β GO:0034272, goa_status more_specific_than_existing_goa; ancestors GO:0035032 / GO:0016236 context_only.more_specific_than_existing_goa. Review handles this via MODIFY of GO:0032991 β proposed_replacement GO:0034272 (rather than a standalone NEW row). GO:0034272 verified real. Review also adds membrane-fission (GO:0090148) and positive regulation of membrane tubulation (GO:1903527) as core β both verified real, non-obsolete, and beyond the PN story. Verdict: ADD/refine to GO:0034272 (review does via MODIFY) β aligned with PN.part_of for an associating membrane-fission adaptor is defensible but borderline vs. an associated/recruitment relation β review flags this in suggested_questions. Ancestors correctly held too_broad.This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
id: Q9Y371
gene_symbol: SH3GLB1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
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.
alternative_products:
- name: '1'
id: Q9Y371-1
- name: '2'
id: Q9Y371-2
sequence_note: VSP_009276
- name: '3'
id: Q9Y371-3
sequence_note: VSP_044895
existing_annotations:
- term:
id: GO:0006897
label: endocytosis
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Endocytosis is directionally related but too broad for SH3GLB1.
action: MODIFY
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_replacement_terms:
- id: GO:0090148
label: membrane fission
- id: GO:0032801
label: receptor catabolic process
additional_reference_ids:
- PMID:20643123
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:20643123
supporting_text: regulates both receptor degradation and cytokinesis
- term:
id: GO:0016020
label: membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Membrane is true but too broad for a peripheral N-BAR autophagy/mitochondrial membrane factor.
action: MODIFY
reason: 'Use the supported specific membrane locations: Golgi membrane, autophagosome membrane, and mitochondrial
outer membrane, with the mitochondrial branch retained as non-core.'
proposed_replacement_terms:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- PMID:17891140
- PMID:21068542
- PMID:15452144
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Golgi apparatus membrane
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Mitochondrion outer membrane
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasmic vesicle, autophagosome
- term:
id: GO:0030674
label: protein-macromolecule adaptor activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: Protein-macromolecule adaptor activity is a good core molecular-function description for Bif-1.
action: ACCEPT
reason: SH3GLB1 uses BAR/SH3-mediated membrane and protein interactions to connect UVRAG/BECN1/PI3KC3-C2
with autophagy membrane remodeling.
additional_reference_ids:
- PMID:17891140
- PMID:20643123
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene
(UVRAG)
- reference_id: PMID:20643123
supporting_text: specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG; UVRAG bridges the interaction to BECN1
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: complex II (PI3KC3-C2)
- reference_id: PMID:11604418
supporting_text: directly bind and evaginate lipid bilayers into narrow tubules
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: induce membrane curvature and bind curved membranes
- term:
id: GO:0061024
label: membrane organization
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Membrane organization is supported but should be represented by the more specific
fission/tubulation terms.
action: MODIFY
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_replacement_terms:
- id: GO:0090148
label: membrane fission
- id: GO:1903527
label: positive regulation of membrane tubulation
additional_reference_ids:
- PMID:11604418
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11604418
supporting_text: directly bind and evaginate lipid bilayers into narrow tubules
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: induce membrane curvature and bind curved membranes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: N-BAR domain
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Golgi membrane localization is core for Bif-1-mediated ATG9 trafficking.
action: ACCEPT
reason: SH3GLB1 localizes to Golgi membranes and drives starvation-induced Atg9-positive Golgi membrane
fission for autophagosome biogenesis.
additional_reference_ids:
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:0000421
label: autophagosome membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Autophagosome membrane localization is core for SH3GLB1/Bif-1 autophagy function.
action: ACCEPT
reason: Bif-1 localizes to autophagosomes after nutrient deprivation and supports autophagosome formation
through UVRAG/PI3KC3-C2.
additional_reference_ids:
- PMID:17891140
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: localizes to autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasmic vesicle, autophagosome
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1.
action: KEEP_AS_NON_CORE
reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as
broad context only.
proposed_replacement_terms:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasm {ECO:0000269|PubMed:15452144}
- term:
id: GO:0005741
label: mitochondrial outer membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Mitochondrial outer membrane localization is supported but non-core for this PN review.
action: KEEP_AS_NON_CORE
reason: SH3GLB1 has a real mitochondrial morphology/apoptosis branch, but the PN-relevant core is
PI3KC3-C2/autophagosome assembly.
additional_reference_ids:
- PMID:15452144
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:15452144
supporting_text: required for maintenance of mitochondrial morphology
- reference_id: PMID:15452144
supporting_text: required for the regulation of the outer mitochondrial membrane dynamics
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: May be required for normal outer mitochondrial membrane dynamics
- term:
id: GO:0030496
label: midbody
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Midbody localization is supported for the PI3KC3-C2/BIF-1 cytokinesis branch but non-core.
action: KEEP_AS_NON_CORE
reason: The cytokinesis/midbody role is real but separate from the autophagy/ATG9 membrane fission core.
additional_reference_ids:
- PMID:20643123
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:20643123
supporting_text: regulates both receptor degradation and cytokinesis
- reference_id: PMID:20643123
supporting_text: strong localisation of these proteins to the midbody
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17891140
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20562859
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21988832
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23414517
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24056303
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25910212
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27107012
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31515488
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32814053
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33961781
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35271311
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:39526800
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:40205054
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:20562859
qualifier: enables
review:
summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology.
action: MODIFY
reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the
homodimerization term is more specific.
proposed_replacement_terms:
- id: GO:0042803
label: protein homodimerization activity
additional_reference_ids:
- PMID:11161816
- PMID:19805544
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11161816
supporting_text: SH3GLB, a new endophilin-related protein family featuring an SH3 domain
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Homodimer, and heterodimer with SH3GLB2
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:23414517
qualifier: enables
review:
summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology.
action: MODIFY
reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the
homodimerization term is more specific.
proposed_replacement_terms:
- id: GO:0042803
label: protein homodimerization activity
additional_reference_ids:
- PMID:11161816
- PMID:19805544
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11161816
supporting_text: SH3GLB, a new endophilin-related protein family featuring an SH3 domain
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Homodimer, and heterodimer with SH3GLB2
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
qualifier: enables
review:
summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology.
action: MODIFY
reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the
homodimerization term is more specific.
proposed_replacement_terms:
- id: GO:0042803
label: protein homodimerization activity
additional_reference_ids:
- PMID:11161816
- PMID:19805544
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11161816
supporting_text: SH3GLB, a new endophilin-related protein family featuring an SH3 domain
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Homodimer, and heterodimer with SH3GLB2
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
qualifier: enables
review:
summary: Identical protein binding is too generic for SH3GLB1 oligomerization biology.
action: MODIFY
reason: SH3GLB1 forms homodimers/oligomers as part of endophilin membrane-curvature function; the
homodimerization term is more specific.
proposed_replacement_terms:
- id: GO:0042803
label: protein homodimerization activity
additional_reference_ids:
- PMID:11161816
- PMID:19805544
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11161816
supporting_text: SH3GLB, a new endophilin-related protein family featuring an SH3 domain
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Homodimer, and heterodimer with SH3GLB2
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
- term:
id: GO:0005504
label: fatty acid binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: Fatty acid binding is supported as older endophilin B isoform biochemistry but is non-core.
action: KEEP_AS_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.
additional_reference_ids:
- PMID:12456676
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:12456676
supporting_text: binds to palmitoyl-CoA
- reference_id: PMID:12456676
supporting_text: exhibits lysophosphatidic acid acyl transferase activity
- reference_id: PMID:12456676
supporting_text: brain-specific
- term:
id: GO:0010508
label: positive regulation of autophagy
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: Positive regulation of autophagy is a core SH3GLB1/Bif-1 annotation.
action: ACCEPT
reason: Bif-1 activates PI3KC3 through UVRAG/BECN1 context, localizes to autophagosomes, and loss of Bif-1
suppresses autophagosome formation.
additional_reference_ids:
- PMID:17891140
- PMID:21068542
- PMID:21499257
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Activates lipid kinase activity of PIK3C3
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: probably by associating with the PI3K complex II
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: located_in
review:
summary: Membrane is true but too broad for a peripheral N-BAR autophagy/mitochondrial membrane factor.
action: MODIFY
reason: 'Use the supported specific membrane locations: Golgi membrane, autophagosome membrane, and mitochondrial
outer membrane, with the mitochondrial branch retained as non-core.'
proposed_replacement_terms:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- PMID:17891140
- PMID:21068542
- PMID:15452144
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Golgi apparatus membrane
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Mitochondrion outer membrane
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasmic vesicle, autophagosome
- term:
id: GO:0032991
label: protein-containing complex
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: part_of
review:
summary: Protein-containing complex is too generic for SH3GLB1 in the PI3KC3-C2 branch.
action: MODIFY
reason: Bif-1 associates with UVRAG/BECN1/PI3KC3-C2; the type II class III PI3K complex term is the
appropriate PN-specific replacement.
proposed_replacement_terms:
- id: GO:0034272
label: phosphatidylinositol 3-kinase complex, class III, type II
additional_reference_ids:
- PMID:17891140
- PMID:20643123
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene
(UVRAG)
- reference_id: PMID:20643123
supporting_text: specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG; UVRAG bridges the interaction to BECN1
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: complex II (PI3KC3-C2)
- term:
id: GO:0042171
label: lysophosphatidic acid acyltransferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: Lysophosphatidic acid acyltransferase activity is supported for endophilin B1 isoform/family
biochemistry but is non-core.
action: KEEP_AS_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.
additional_reference_ids:
- PMID:12456676
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:12456676
supporting_text: binds to palmitoyl-CoA
- reference_id: PMID:12456676
supporting_text: exhibits lysophosphatidic acid acyl transferase activity
- reference_id: PMID:12456676
supporting_text: brain-specific
- term:
id: GO:0048102
label: autophagic cell death
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: Autophagic cell death overstates the supported Bif-1 autophagy/apoptosis evidence.
action: MARK_AS_OVER_ANNOTATED
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_replacement_terms:
- id: GO:0010508
label: positive regulation of autophagy
- id: GO:2000786
label: positive regulation of autophagosome assembly
additional_reference_ids:
- PMID:17891140
- PMID:16227588
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: PMID:16227588
supporting_text: interacts with Bax
- reference_id: PMID:16227588
supporting_text: important component of the mitochondrial pathway for apoptosis
- term:
id: GO:0141038
label: phosphatidylinositol 3-kinase activator activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: enables
review:
summary: PI3K activator activity is core for SH3GLB1/Bif-1.
action: ACCEPT
reason: Bif-1 activates PI3KC3 via the UVRAG/Beclin1 PI3KC3-C2 context during autophagy.
additional_reference_ids:
- PMID:17891140
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Activates lipid kinase activity of PIK3C3
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: probably by associating with the PI3K complex II
- reference_id: PMID:17891140
supporting_text: interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene
(UVRAG)
- reference_id: PMID:20643123
supporting_text: specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1
- term:
id: GO:1903778
label: protein localization to vacuolar membrane
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: Protein localization to vacuolar membrane should be humanized/narrowed to autophagosome membrane
and autophagosome assembly.
action: MODIFY
reason: The human evidence is Atg9 trafficking from Golgi membranes toward autophagosome biogenesis, not a
generic vacuolar membrane localization process.
proposed_replacement_terms:
- id: GO:2000786
label: positive regulation of autophagosome assembly
- id: GO:0000421
label: autophagosome membrane
additional_reference_ids:
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:2000786
label: positive regulation of autophagosome assembly
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: Positive regulation of autophagosome assembly is a core SH3GLB1 process.
action: ACCEPT
reason: Bif-1/Endophilin B1 promotes Atg9-positive Golgi membrane fission and PI3KC3-C2-dependent
autophagosome biogenesis.
additional_reference_ids:
- PMID:17891140
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:0005829
label: cytosol
evidence_type: IDA
original_reference_id: GO_REF:0000052
qualifier: located_in
review:
summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1.
action: KEEP_AS_NON_CORE
reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as
broad context only.
proposed_replacement_terms:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasm {ECO:0000269|PubMed:15452144}
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: EXP
original_reference_id: PMID:21068542
qualifier: located_in
review:
summary: Golgi membrane localization is core for Bif-1-mediated ATG9 trafficking.
action: ACCEPT
reason: SH3GLB1 localizes to Golgi membranes and drives starvation-induced Atg9-positive Golgi membrane
fission for autophagosome biogenesis.
additional_reference_ids:
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:0031334
label: positive regulation of protein-containing complex assembly
evidence_type: IDA
original_reference_id: PMID:19074440
qualifier: involved_in
review:
summary: Positive regulation of protein-containing complex assembly is supported in Bax activation context
but non-core.
action: KEEP_AS_NON_CORE
reason: This row reflects Bif-1/Bax apoptotic membrane-permeabilization biology rather than the PN
autophagy core.
additional_reference_ids:
- PMID:19074440
- PMID:16227588
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:19074440
supporting_text: stimulatory effect of Bif-1 on BAX-driven MOMP
- reference_id: PMID:19074440
supporting_text: BAX conformational activation
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- term:
id: GO:0032991
label: protein-containing complex
evidence_type: IDA
original_reference_id: PMID:19805544
qualifier: part_of
review:
summary: Protein-containing complex is too generic for Bax-induced Endo B1 oligomerization.
action: MODIFY
reason: The cited evidence supports Endo B1 oligomerization/lipid vesiculation in apoptosis, not a stable
named complex term.
proposed_replacement_terms:
- id: GO:0042803
label: protein homodimerization activity
additional_reference_ids:
- PMID:19805544
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
- reference_id: PMID:19805544
supporting_text: massive vesiculation of liposomes
- term:
id: GO:0045296
label: cadherin binding
evidence_type: HDA
original_reference_id: PMID:25468996
qualifier: enables
review:
summary: Cadherin binding is a high-throughput interaction over-annotation for SH3GLB1.
action: MARK_AS_OVER_ANNOTATED
reason: The HDA interactome row does not define SH3GLB1 core function; no supporting SH3GLB1 cadherin
mechanism is evident from the curated functional record.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Endophilin-B1
- term:
id: GO:0031647
label: regulation of protein stability
evidence_type: HMP
original_reference_id: PMID:24270810
qualifier: involved_in
review:
summary: Regulation of protein stability from a high-throughput mitophagy screen is not a core SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
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.
additional_reference_ids:
- PMID:24270810
- PMID:15452144
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:24270810
supporting_text: genome-wide small interfering RNA (siRNA) screens
- reference_id: PMID:15452144
supporting_text: required for maintenance of mitochondrial morphology
- term:
id: GO:1903749
label: positive regulation of protein localization to mitochondrion
evidence_type: HMP
original_reference_id: PMID:24270810
qualifier: involved_in
review:
summary: Positive regulation of protein localization to mitochondrion is a high-throughput
mitophagy-screen overextension.
action: MARK_AS_OVER_ANNOTATED
reason: SH3GLB1 has supported mitochondrial outer membrane dynamics, but this HMP process term is not the
best representation of its function.
proposed_replacement_terms:
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- PMID:24270810
- PMID:15452144
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:24270810
supporting_text: parkin translocation to damaged mitochondria
- reference_id: PMID:15452144
supporting_text: required for the regulation of the outer mitochondrial membrane dynamics
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:25468996
qualifier: located_in
review:
summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1.
action: KEEP_AS_NON_CORE
reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as
broad context only.
proposed_replacement_terms:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasm {ECO:0000269|PubMed:15452144}
- term:
id: GO:0016241
label: regulation of macroautophagy
evidence_type: TAS
original_reference_id: PMID:21499257
qualifier: involved_in
review:
summary: Regulation of macroautophagy is supported and core but less specific than the PI3KC3-C2/ATG9
mechanism.
action: ACCEPT
reason: Cdk5 phosphorylation and Bif-1/PI3KC3-C2 studies support induced autophagy; the detailed mechanism
is positive regulation of autophagosome assembly.
additional_reference_ids:
- PMID:21499257
- PMID:17891140
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21499257
supporting_text: required for induced autophagy
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: required for autophagy induction in starved neurons
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- term:
id: GO:0034198
label: cellular response to amino acid starvation
evidence_type: IMP
original_reference_id: PMID:21068542
qualifier: involved_in
review:
summary: Amino-acid starvation response is the experimental context for Bif-1 autophagy induction and is
non-core.
action: KEEP_AS_NON_CORE
reason: The functional annotation should emphasize ATG9 trafficking/autophagosome assembly rather than the
starvation stimulus itself.
additional_reference_ids:
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- term:
id: GO:0042149
label: cellular response to glucose starvation
evidence_type: IMP
original_reference_id: PMID:21068542
qualifier: involved_in
review:
summary: Glucose starvation response is an experimental context for Bif-1 autophagy induction and is
non-core.
action: KEEP_AS_NON_CORE
reason: The core process is starvation-induced ATG9/Golgi membrane fission and autophagosome assembly, not
glucose starvation response per se.
additional_reference_ids:
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- term:
id: GO:0090148
label: membrane fission
evidence_type: IMP
original_reference_id: PMID:21068542
qualifier: involved_in
review:
summary: Membrane fission is a core Bif-1/endophilin B1 process in ATG9 trafficking.
action: ACCEPT
reason: Bif-1 N-BAR-dependent Golgi membrane fission supplies Atg9-positive membranes for autophagosome
formation.
additional_reference_ids:
- PMID:11604418
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11604418
supporting_text: directly bind and evaginate lipid bilayers into narrow tubules
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: induce membrane curvature and bind curved membranes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: N-BAR domain
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:1903527
label: positive regulation of membrane tubulation
evidence_type: IMP
original_reference_id: PMID:21068542
qualifier: involved_in
review:
summary: Positive regulation of membrane tubulation is core for the N-BAR domain-mediated autophagy
membrane source role.
action: ACCEPT
reason: The N-BAR domain drives membrane binding/tubulation, and Bif-1-dependent Golgi
tubulation/fragmentation supports ATG9 trafficking during autophagy.
additional_reference_ids:
- PMID:11604418
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11604418
supporting_text: directly bind and evaginate lipid bilayers into narrow tubules
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: induce membrane curvature and bind curved membranes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: N-BAR domain
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- term:
id: GO:1903778
label: protein localization to vacuolar membrane
evidence_type: IMP
original_reference_id: PMID:21068542
qualifier: involved_in
review:
summary: Protein localization to vacuolar membrane should be humanized/narrowed to autophagosome membrane
and autophagosome assembly.
action: MODIFY
reason: The human evidence is Atg9 trafficking from Golgi membranes toward autophagosome biogenesis, not a
generic vacuolar membrane localization process.
proposed_replacement_terms:
- id: GO:2000786
label: positive regulation of autophagosome assembly
- id: GO:0000421
label: autophagosome membrane
additional_reference_ids:
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:2000786
label: positive regulation of autophagosome assembly
evidence_type: IMP
original_reference_id: PMID:21068542
qualifier: involved_in
review:
summary: Positive regulation of autophagosome assembly is a core SH3GLB1 process.
action: ACCEPT
reason: Bif-1/Endophilin B1 promotes Atg9-positive Golgi membrane fission and PI3KC3-C2-dependent
autophagosome biogenesis.
additional_reference_ids:
- PMID:17891140
- PMID:21068542
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- term:
id: GO:0000421
label: autophagosome membrane
evidence_type: IDA
original_reference_id: PMID:17891140
qualifier: located_in
review:
summary: Autophagosome membrane localization is core for SH3GLB1/Bif-1 autophagy function.
action: ACCEPT
reason: Bif-1 localizes to autophagosomes after nutrient deprivation and supports autophagosome formation
through UVRAG/PI3KC3-C2.
additional_reference_ids:
- PMID:17891140
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: localizes to autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasmic vesicle, autophagosome
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- term:
id: GO:0010508
label: positive regulation of autophagy
evidence_type: IMP
original_reference_id: PMID:17891140
qualifier: involved_in
review:
summary: Positive regulation of autophagy is a core SH3GLB1/Bif-1 annotation.
action: ACCEPT
reason: Bif-1 activates PI3KC3 through UVRAG/BECN1 context, localizes to autophagosomes, and loss of Bif-1
suppresses autophagosome formation.
additional_reference_ids:
- PMID:17891140
- PMID:21068542
- PMID:21499257
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Activates lipid kinase activity of PIK3C3
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: probably by associating with the PI3K complex II
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- term:
id: GO:0030496
label: midbody
evidence_type: IDA
original_reference_id: PMID:20643123
qualifier: located_in
review:
summary: Midbody localization is supported for the PI3KC3-C2/BIF-1 cytokinesis branch but non-core.
action: KEEP_AS_NON_CORE
reason: The cytokinesis/midbody role is real but separate from the autophagy/ATG9 membrane fission core.
additional_reference_ids:
- PMID:20643123
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:20643123
supporting_text: regulates both receptor degradation and cytokinesis
- reference_id: PMID:20643123
supporting_text: strong localisation of these proteins to the midbody
- term:
id: GO:0032465
label: regulation of cytokinesis
evidence_type: IMP
original_reference_id: PMID:20643123
qualifier: involved_in
review:
summary: Regulation of cytokinesis is supported but non-core.
action: KEEP_AS_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.
additional_reference_ids:
- PMID:20643123
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:20643123
supporting_text: regulates both receptor degradation and cytokinesis
- reference_id: PMID:20643123
supporting_text: strong localisation of these proteins to the midbody
- term:
id: GO:0032801
label: receptor catabolic process
evidence_type: IMP
original_reference_id: PMID:20643123
qualifier: involved_in
review:
summary: Receptor catabolic process is supported but non-core.
action: KEEP_AS_NON_CORE
reason: BIF-1-containing PI3KC3-C2 contributes to degradative endocytic traffic, but the PN core is
autophagy/ATG9 membrane fission.
additional_reference_ids:
- PMID:20643123
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:20643123
supporting_text: regulates both receptor degradation and cytokinesis
- reference_id: PMID:20643123
supporting_text: growth factor receptor degradation
- term:
id: GO:0048102
label: autophagic cell death
evidence_type: IMP
original_reference_id: PMID:17891140
qualifier: involved_in
review:
summary: Autophagic cell death overstates the supported Bif-1 autophagy/apoptosis evidence.
action: MARK_AS_OVER_ANNOTATED
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_replacement_terms:
- id: GO:0010508
label: positive regulation of autophagy
- id: GO:2000786
label: positive regulation of autophagosome assembly
additional_reference_ids:
- PMID:17891140
- PMID:16227588
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- reference_id: PMID:16227588
supporting_text: interacts with Bax
- reference_id: PMID:16227588
supporting_text: important component of the mitochondrial pathway for apoptosis
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11161816
qualifier: enables
review:
summary: The interaction evidence may be real, but generic protein binding is not an informative SH3GLB1
function.
action: MARK_AS_OVER_ANNOTATED
reason: Replace generic protein binding with specific adaptor activity, PI3KC3-C2 association,
homodimerization, membrane curvature/fission, or Bax/mitochondrial apoptosis context as appropriate.
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds BAX
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:11161816
qualifier: located_in
review:
summary: Cytoplasmic/cytosolic localization is broad but compatible with SH3GLB1.
action: KEEP_AS_NON_CORE
reason: More specific membrane locations drive the functional review; cytoplasm/cytosol is retained as
broad context only.
proposed_replacement_terms:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
- id: GO:0005741
label: mitochondrial outer membrane
additional_reference_ids:
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Cytoplasm {ECO:0000269|PubMed:15452144}
- term:
id: GO:0042803
label: protein homodimerization activity
evidence_type: IPI
original_reference_id: PMID:11161816
qualifier: enables
review:
summary: Protein homodimerization is supported and relevant to endophilin BAR-domain membrane remodeling.
action: ACCEPT
reason: SH3GLB1 homodimer/oligomer formation is part of the endophilin membrane-curvature mechanism and is
more specific than identical protein binding.
additional_reference_ids:
- PMID:11161816
- PMID:19805544
- file:human/SH3GLB1/SH3GLB1-uniprot.txt
- file:human/SH3GLB1/SH3GLB1-notes.md
supported_by:
- reference_id: PMID:11161816
supporting_text: SH3GLB, a new endophilin-related protein family featuring an SH3 domain
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Homodimer, and heterodimer with SH3GLB2
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
Compara
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:11161816
title: SH3GLB, a new endophilin-related protein family featuring an SH3 domain.
findings: []
- id: PMID:17891140
title: Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis.
findings: []
- id: PMID:19074440
title: Endophilin B1/Bif-1 stimulates BAX activation independently from its capacity to produce large scale
membrane morphological rearrangements.
findings: []
- id: PMID:19805544
title: Bax activates endophilin B1 oligomerization and lipid membrane vesiculation.
findings: []
- id: PMID:20562859
title: Network organization of the human autophagy system.
findings: []
- id: PMID:20643123
title: A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and
BIF-1 regulates cytokinesis and degradative endocytic traffic.
findings: []
- id: PMID:21068542
title: Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy.
findings: []
- id: PMID:21499257
title: Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of
Parkinson's disease.
findings: []
- id: PMID:21988832
title: Toward an understanding of the protein interaction network of the human liver.
findings: []
- id: PMID:23414517
title: 'A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.'
findings: []
- id: PMID:24056303
title: PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential
interactions with the ER tether and the beclinΒ 1 complex.
findings: []
- id: PMID:24270810
title: High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy.
findings: []
- id: PMID:25416956
title: A proteome-scale map of the human interactome network.
findings: []
- id: PMID:25468996
title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
findings: []
- id: PMID:25910212
title: Widespread macromolecular interaction perturbations in human genetic disorders.
findings: []
- id: PMID:27107012
title: Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
findings: []
- id: PMID:31515488
title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum
in human populations.
findings: []
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings: []
- id: PMID:32814053
title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread
Protein Aggregation in Affected Brains.
findings: []
- id: PMID:33961781
title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
findings: []
- id: PMID:35271311
title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
findings: []
- id: PMID:39526800
title: A comprehensive two-hybrid analysis to explore the Legionella pneumophila effector-effector
interactome.
findings: []
- id: PMID:40205054
title: Multimodal cell maps as a foundation for structural and functional genomics.
findings: []
- id: PMID:11259440
title: Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein
that associates with Bax.
findings: []
- id: PMID:11604418
title: Generation of high curvature membranes mediated by direct endophilin bilayer interactions.
findings: []
- id: PMID:12456676
title: Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl
transferase with properties distinct from endophilin A1.
findings: []
- id: PMID:15452144
title: Endophilin B1 is required for the maintenance of mitochondrial morphology.
findings: []
- id: PMID:16227588
title: Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis.
findings: []
- id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
title: UniProtKB record for human SH3GLB1
findings: []
- id: file:human/SH3GLB1/SH3GLB1-notes.md
title: SH3GLB1 review notes
findings: []
core_functions:
- molecular_function:
id: GO:0030674
label: protein-macromolecule adaptor activity
description: SH3GLB1/Bif-1 acts as a BAR/SH3 adaptor that connects UVRAG/BECN1/PI3KC3-C2 to autophagy
membrane remodeling and ATG9-positive Golgi membrane trafficking.
directly_involved_in:
- id: GO:0010508
label: positive regulation of autophagy
- id: GO:2000786
label: positive regulation of autophagosome assembly
- id: GO:0090148
label: membrane fission
- id: GO:1903527
label: positive regulation of membrane tubulation
locations:
- id: GO:0000139
label: Golgi membrane
- id: GO:0000421
label: autophagosome membrane
in_complex:
id: GO:0034272
label: phosphatidylinositol 3-kinase complex, class III, type II
supported_by:
- &id005
reference_id: PMID:17891140
supporting_text: interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene
(UVRAG)
- &id006
reference_id: PMID:20643123
supporting_text: specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Interacts with UVRAG; UVRAG bridges the interaction to BECN1
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: complex II (PI3KC3-C2)
- &id001
reference_id: PMID:17891140
supporting_text: functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3)
- &id002
reference_id: PMID:17891140
supporting_text: loss of Bif-1 suppresses autophagosome formation
- &id003
reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Activates lipid kinase activity of PIK3C3
- &id004
reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: probably by associating with the PI3K complex II
- reference_id: PMID:21068542
supporting_text: tubulation and fragmentation of Atg9-positive Golgi membranes
- reference_id: PMID:21068542
supporting_text: Bif-1/Endophilin B1 and the PI3KC3 complex II
- reference_id: PMID:21068542
supporting_text: the fission of Golgi membranes and the trafficking of Atg9 from the Golgi complex to
autophagosomes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: regulate the trafficking of ATG9A from the Golgi complex
- molecular_function:
id: GO:0141038
label: phosphatidylinositol 3-kinase activator activity
description: Bif-1 positively regulates PIK3C3/VPS34 lipid kinase activity through the UVRAG-containing
PI3KC3-C2 autophagy complex.
directly_involved_in:
- id: GO:0010508
label: positive regulation of autophagy
- id: GO:2000786
label: positive regulation of autophagosome assembly
locations:
- id: GO:0000421
label: autophagosome membrane
in_complex:
id: GO:0034272
label: phosphatidylinositol 3-kinase complex, class III, type II
supported_by:
- *id001
- *id002
- *id003
- *id004
- *id005
- *id006
- molecular_function:
id: GO:0042803
label: protein homodimerization activity
description: Endophilin B1 dimerization/oligomerization supports N-BAR membrane curvature, tubulation, and
fission functions relevant to autophagy membrane supply and mitochondrial membrane remodeling.
directly_involved_in:
- id: GO:1903527
label: positive regulation of membrane tubulation
- id: GO:0090148
label: membrane fission
locations:
- id: GO:0000139
label: Golgi membrane
- id: GO:0005741
label: mitochondrial outer membrane
supported_by:
- reference_id: PMID:11161816
supporting_text: SH3GLB, a new endophilin-related protein family featuring an SH3 domain
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: Homodimer, and heterodimer with SH3GLB2
- reference_id: PMID:19805544
supporting_text: Endo B1 oligomerization is induced by Bax
- reference_id: PMID:11604418
supporting_text: directly bind and evaginate lipid bilayers into narrow tubules
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: induce membrane curvature and bind curved membranes
- reference_id: file:human/SH3GLB1/SH3GLB1-uniprot.txt
supporting_text: N-BAR domain
proposed_new_terms: []
suggested_questions:
- question: 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?
experts:
- GO autophagy editors
- ComplexPortal curators
- Reactome autophagy curators
- question: 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?
experts:
- GO autophagy editors
- membrane trafficking experts
- question: Should autophagic cell death annotations for Bif-1 be replaced by positive regulation of autophagy
plus separate Bax/Bak mitochondrial apoptosis annotations?
experts:
- GO apoptosis editors
- GO autophagy editors
suggested_experiments:
- description: 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.
experiment_type: Bif-1 autophagy membrane-fission rescue assay
hypothesis: Bif-1 requires both N-BAR membrane remodeling and SH3-dependent UVRAG/PI3KC3-C2 engagement to
support Atg9 trafficking and autophagosome assembly.
- description: Compare wild type and Bax-binding/mitochondrial-targeting SH3GLB1 mutants for mitochondrial
morphology, Bax/Bak activation, and autophagic flux in the same background.
experiment_type: separation-of-function apoptosis versus autophagy assay
hypothesis: SH3GLB1 mitochondrial apoptosis and PI3KC3-C2 autophagy roles are genetically separable.