SH3GLB1

UniProt ID: Q9Y371
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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.

Existing Annotations Review

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Core Functions

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.

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: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
  • 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

Bif-1 positively regulates PIK3C3/VPS34 lipid kinase activity through the UVRAG-containing PI3KC3-C2 autophagy complex.

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

Endophilin B1 dimerization/oligomerization supports N-BAR membrane curvature, tubulation, and fission functions relevant to autophagy membrane supply and mitochondrial membrane remodeling.

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
  • 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

References

Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
SH3GLB, a new endophilin-related protein family featuring an SH3 domain.
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis.
Endophilin B1/Bif-1 stimulates BAX activation independently from its capacity to produce large scale membrane morphological rearrangements.
Bax activates endophilin B1 oligomerization and lipid membrane vesiculation.
Network organization of the human autophagy system.
A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic.
Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy.
Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease.
Toward an understanding of the protein interaction network of the human liver.
A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.
PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclinΒ 1 complex.
High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy.
A proteome-scale map of the human interactome network.
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
Widespread macromolecular interaction perturbations in human genetic disorders.
Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
A comprehensive two-hybrid analysis to explore the Legionella pneumophila effector-effector interactome.
Multimodal cell maps as a foundation for structural and functional genomics.
Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax.
Generation of high curvature membranes mediated by direct endophilin bilayer interactions.
Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1.
Endophilin B1 is required for the maintenance of mitochondrial morphology.
Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis.
file:human/SH3GLB1/SH3GLB1-uniprot.txt
UniProtKB record for human SH3GLB1
file:human/SH3GLB1/SH3GLB1-notes.md
SH3GLB1 review notes

Suggested Questions for Experts

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

Suggested Experiments

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

πŸ“š Additional Documentation

Notes

(SH3GLB1-notes.md)

SH3GLB1 review notes

Scope

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.

Evidence synthesis

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.

Curation calls

  • Core: protein-macromolecule adaptor activity, PI3K activator activity, positive regulation of autophagy/autophagosome assembly, membrane fission/tubulation, autophagosome membrane, and Golgi membrane/ATG9 trafficking.
  • Modify generic complex annotations (GO:0032991 protein-containing complex) toward GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II where supported by UVRAG/BECN1/PI3KC3-C2 evidence.
  • Generic 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.
  • Keep mitochondrial outer membrane, mitochondrial morphology/protein-targeting, Bax/apoptosis, receptor catabolic process, and cytokinesis/midbody as non-core.
  • Treat 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

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.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: the prior wording framed the PI3KC3 activation, UVRAG/Beclin 1 association, and Golgi/autophagosome membrane fission/tubulation roles specifically in the Proteostasis Network class III PI3K complex 2 context.

Pn Notes

(SH3GLB1-pn-notes.md)

SH3GLB1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y371
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • 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.
  • Existing/core annotation action counts: ACCEPT: 14; KEEP_AS_NON_CORE: 14; MARK_AS_OVER_ANNOTATED: 21; MODIFY: 12

PN Consistency Summary

  • Consistency: Consistent. Notes, review, and PN agree SH3GLB1/Bif-1/endophilin B1 is a POSITIVE N-BAR/SH3 adaptor that activates PI3KC3 via UVRAG (PMID:17891140) and drives ATG9/Golgi membrane fission (PMID:21068542). PN Notes ("binds to UVRAG and promotes activity") correctly state the positive direction β€” contrast with the RUBCNL row, which was mislabeled. No contradictions.
  • PN story / NEW pressure: PN asserts GO:0034272 membership. GOA has only generic GO:0032991 (protein-containing complex, IDA+IEA), so GO:0034272 is 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.
  • Evidence alignment: PN cites Annual Review, a cardiovascular review, and PMID:19270696. Review uses primary PMID:17891140 (Bif-1/UVRAG autophagy), 21068542 (ATG9/Golgi fission), 11604418 (endophilin membrane tubulation), 15452144/16227588 (mitochondria/Bax, non-core), 12456676 (LPAAT, non-core). PMID:19270696 is not cited in this review; the PN reference list is shared-branch boilerplate, only loosely SH3GLB1-specific.
  • Verdict: Consistent; PN GO:0034272 refines the gene's generic GO:0032991 (more_specific) and the review captures it via MODIFY plus richer membrane-fission/tubulation MF/BP terms (all verified). No edits required.

Full Consistency Review

  • UniProt: Q9Y371 Β· batch: proteostasis-pr-1217 Β· review status: COMPLETE
  • PN placement: 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.
  • Consistency: Consistent. Notes, review, and PN agree SH3GLB1/Bif-1/endophilin B1 is a POSITIVE N-BAR/SH3 adaptor that activates PI3KC3 via UVRAG (PMID:17891140) and drives ATG9/Golgi membrane fission (PMID:21068542). PN Notes ("binds to UVRAG and promotes activity") correctly state the positive direction β€” contrast with the RUBCNL row, which was mislabeled. No contradictions.
  • PN story / NEW pressure: PN asserts GO:0034272 membership. GOA has only generic GO:0032991 (protein-containing complex, IDA+IEA), so GO:0034272 is 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.
  • Mapping strategy: Supports the C2-component mapping; the PN-projected GO:0034272 is NARROWER than the gene's existing generic GO:0032991, which is exactly the intended refinement (not an over-broad projection). As with the other C2 binders, 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.
  • Evidence alignment: PN cites Annual Review, a cardiovascular review, and PMID:19270696. Review uses primary PMID:17891140 (Bif-1/UVRAG autophagy), 21068542 (ATG9/Golgi fission), 11604418 (endophilin membrane tubulation), 15452144/16227588 (mitochondria/Bax, non-core), 12456676 (LPAAT, non-core). PMID:19270696 is not cited in this review; the PN reference list is shared-branch boilerplate, only loosely SH3GLB1-specific.
  • Verdict: Consistent; PN GO:0034272 refines the gene's generic GO:0032991 (more_specific) and the review captures it via MODIFY plus richer membrane-fission/tubulation MF/BP terms (all verified). No edits required.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/SH3GLB1/SH3GLB1-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Class 3 PI3K complex 2, direct | Class 3 PI3K complex 2 component

  • UniProt: Q9Y371
  • In branches: ALP
  • Notes: Member of class III PI3K complex 2 that binds to UVRAG and promotes activity
  • PN references (titles):
    • Mammalian Autophagy: How Does It Work? | Annual Review of Biochemistry (annualreviews.org)
    • role of autophagy in cardiovascular pathology | Cardiovascular Research | Oxford Academic (oup.com)
    • Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages | Nature Cell Biology
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Class 3 PI3K complex 2 component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II]
      rationale: This PN type denotes component membership in the direct class III PI3K complex 2 module used during autophagosome maturation and lysosome fusion. The corresponding GO complex term is the right propagation target.
    • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct
      status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
      rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
    • [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Class 3 PI3K complex 2 component

Note

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.

πŸ“„ View Raw YAML

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.