BIN1 (amphiphysin II) is a peripheral membrane and cytoskeletal adaptor whose N-BAR domain binds phospholipids, senses membrane curvature and deforms membranes into tubules. Alternative splicing changes its membrane-targeting and interaction regions, giving neuronal, muscle and more widely expressed forms distinct properties. BIN1 membrane shaping is central to skeletal-muscle T-tubule organization and contributes to endocytic membrane remodeling. Its SH3 domain recruits partners including dynamin, while CLAP-containing forms interact with clathrin-associated machinery. Contacts with actin, nesprins and CLIP170 link membranes and the nuclear envelope to the cytoskeleton. Additional interactions with MYC, tau, intracellular clusterin and BACE1 connect particular BIN1 forms to growth regulation and neuronal protein trafficking. Pathogenic BIN1 variants that disrupt membrane deformation or dynamin recruitment cause centronuclear myopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma-membrane association is integral to BIN1 membrane remodeling. Reason: Selected C2C12 Results show plasma-membrane invaginations induced by BIN1 N-BAR constructs. The IBA is a phylogenetic inference, not a new human direct assay. The original node placement was not independently re-curated, and no lineage-specific loss is asserted. |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the phylogenetic synaptic-vesicle localization. Reason: Selected Results recover endogenous BIN1 with Tau from mouse-brain synaptosomal fractions, corroborating the neuronal vesicle-associated context without making it a universal localization. The IBA is a phylogenetic inference, not a new human direct assay. The original node placement was not independently re-curated, and no lineage-specific loss is asserted. |
| GO:0005543 phospholipid binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phospholipid binding underlies BIN1 membrane remodeling. Reason: The human N-BAR helix study reports membrane binding and liposome tubulation; this independently grounds the molecular activity. The IBA is a phylogenetic inference, not a new human direct assay. The original node placement was not independently re-curated, and no lineage-specific loss is asserted. |
| GO:0048156 tau protein binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Tau binding is a supported partner interaction. Reason: Human BIN1-Tau interaction is independently supported by recombinant pull-downs in PMID:23399914 and isoform-dependent SH3 interaction in PMID:28755476. Retain this as a specific neuronal interaction outside the compact membrane-remodeling core. Human BIN1 appearing among the IBA descendant sources is legitimate experimental grounding, not circularity; the PAINT node was not re-curated. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is context dependent. Reason: Retain the UniProt subcellular-location mapping, consistent with nuclear BIN1 in the original MYC study. PMID:9182667 instead finds predominantly cytosolic protein in its transfection conditions and no nuclear enrichment in adult rat brain or muscle. These observations concern different contexts and do not establish a universal nuclear or exclusively cytoplasmic localization. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the inferred cytoplasm localization. Reason: This electronic annotation is consistent with BIN1 membrane-associated adaptor biology and the separately cited localization evidence. It remains an electronic inference; neither the inferred cellular compartment nor the corroborating study is presented as a direct human assay for every isoform. |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the inferred endosomes localization. Reason: This electronic annotation is consistent with BIN1 membrane-associated adaptor biology and the separately cited localization evidence. It remains an electronic inference; neither the inferred cellular compartment nor the corroborating study is presented as a direct human assay for every isoform. |
| GO:0006897 endocytosis | IEA GO_REF:0000117 | ACCEPT | Summary: Endocytosis is a central BIN1 trafficking function. Reason: Retain the ARBA process assertion, corroborated by endocytic interactions and perturbation experiments in PMID:12668730 and the curated clathrin pathway. BIN1 supplies membrane remodeling and partner recruitment rather than dynamin GTP hydrolysis. |
| GO:0016020 membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the inferred membranes localization. Reason: This electronic annotation is consistent with BIN1 membrane-associated adaptor biology and the separately cited localization evidence. It remains an electronic inference; neither the inferred cellular compartment nor the corroborating study is presented as a direct human assay for every isoform. |
| GO:0030100 regulation of endocytosis | IEA GO_REF:0000002 | ACCEPT | Summary: BIN1 regulates endocytic membrane remodeling. Reason: The InterPro inference is consistent with the N-BAR/SH3 architecture and endocytic partner experiments in PMID:12668730. Regulation depends on isoform and expression context; inhibition by an overexpressed isolated SH3 domain is not evidence that every full-length isoform is solely an inhibitor. |
| GO:0030315 T-tubule | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the inferred T-tubules localization. Reason: This electronic annotation is consistent with BIN1 membrane-associated adaptor biology and the separately cited localization evidence. It remains an electronic inference; neither the inferred cellular compartment nor the corroborating study is presented as a direct human assay for every isoform. |
| GO:0030424 axon | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the inferred axonal compartments localization. Reason: This electronic annotation is consistent with BIN1 membrane-associated adaptor biology and the separately cited localization evidence. It remains an electronic inference; neither the inferred cellular compartment nor the corroborating study is presented as a direct human assay for every isoform. |
| GO:0051649 establishment of localization in cell | IEA GO_REF:0000117 | MODIFY | Summary: Refine the broad localization process to established endocytosis. Reason: Establishment of localization in cell is broad but biologically compatible with BIN1. Breadth alone is not over-annotation. Endocytosis is a supported, more informative process in the available evidence and already represented elsewhere in GOA; this replacement adds no independent evidence or new process assertion. ARBA rule placement itself was not audited. Proposed replacements: endocytosis |
| GO:0005515 protein binding | IPI PMID:10903846 Bin2, a functionally nonredundant member of the BAR adaptor ... | KEEP AS NON CORE | Summary: Retain the source-supported BIN2 association as non-core. Reason: The complete PMID10903846 abstract reports a stable cellular BIN2-BIN1 complex dependent on the BAR region, supporting the recorded BIN2/Q9UBW5 association. The exact assayed BIN1 splice form and purified stoichiometry were not reconstructed from the abstract; this does not establish a defined heterodimerization mechanism or a distinct molecular function for this pair. Retain the supported GO:0005515 annotation as KEEP_AS_NON_CORE under the explicit CLINGEN_MENDELIAN project instruction, without extending the assay to every BIN1 isoform. Supporting Evidence: PMID:10903846 Bin2 formed a stable complex in cells with Bin1 |
| GO:0005515 protein binding | IPI PMID:12604805 Identification and characterization of amphiphysin II as a n... | MODIFY | Summary: Refine NS5A binding to proline-rich region binding. Reason: GOA identifies the processed HCV NS5A chain P27958-PRO_0000037576. The complete abstract maps the contact to a C-terminal proline-rich region of NS5A and BIN1 SH3, with endogenous co-precipitation in HuH-7 replicon cells. The recognized motif is on NS5A, so SH3 domain binding would reverse the binding direction. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:12604805 a proline-rich region in the C-terminal part of NS5A |
| GO:0005515 protein binding | IPI PMID:12668730 Sorting nexin 4 and amphiphysin 2, a new partnership between... | UNDECIDED | Summary: SNX4 association is demonstrated with a murine amphiphysin 2 fragment; the human BIN1 assertion remains unresolved. Reason: The cached PMID:12668730 abstract explicitly describes a two-hybrid screen with murine amphiphysin 2 residues 1-304 and reports co-immunoprecipitation confirmation. It does not specify a human BIN1 construct for that confirmation. This establishes a positive family-level interaction but leaves the exact human BIN1-SNX4 IPI assertion unadjudicated. Retain UNDECIDED without asserting absence of human binding or curator misattribution; a human isoform-specific mechanism is not established by the accessible cached evidence. Supporting Evidence: PMID:12668730 This interaction was confirmed in vivo by co-immunoprecipitation |
| GO:0005515 protein binding | IPI PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera... | KEEP AS NON CORE | Summary: The isolated BIN1 SH3 region associates with FBP1, XRCC4 and DLGAP4 in the source-linked assays. Reason: The combined source row covers FBP1/P09467, XRCC4/Q13426 and DLGAP4/Q9Y2H0. The complete PMID16275660 abstract reports peptide-motif mapping for all three. Exact human pair records in IntAct confirm filter binding, pull-down, two-hybrid and peptide-array experiments using the isolated BIN1 SH3 region at residues 497-593, with Table 1 and Figure 4 provenance. Pull-down records EBI-1783903, EBI-1783894 and EBI-1783885 identify FBP1, XRCC4 and DLGAP4, respectively. These source-linked interactions support KEEP_AS_NON_CORE under the explicit CLINGEN_MENDELIAN project instruction. GO:0070064 proline-rich region binding was considered, but the accessible article text and exact assay records do not establish that specificity for the combined partner set. BIN1 providing an SH3 domain does not make BIN1 the protein that binds an SH3 domain. Assay and access limits are documented in the notes. Supporting Evidence: PMID:16275660 binding motifs in the proteins DLP4, XRCC4, and fructose-1,6-bisphosphatase |
| GO:0005515 protein binding | IPI PMID:16530520 The SH3 binding motif of HCV [corrected] NS5A protein intera... | MODIFY | Summary: Refine the NS5A interaction to proline-rich region binding. Reason: GOA records processed HCV chains P27958-PRO_0000037576 and Q9WMX2-PRO_0000037551. The complete abstract reports NS5A binding in vitro and by co-immunoprecipitation, with deletion/mutation dependence on NS5A PxxP motifs and BIN1 SH3. UniProt directly identifies the P27958 chain as NS5A; the exact Q9WMX2 feature could not be independently retrieved in this follow-up. The motif-based refinement is supported by the paper, without claiming that the second chain lookup or the full paper was verified. Viral infection and HepG2 apoptosis outcomes remain distinct from BIN1 core membrane function. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:16530520 the SH3 binding motif of HCV NS5A and SH3 domain of Bin1 are essential for interaction |
| GO:0005515 protein binding | IPI PMID:18647389 The central proline rich region of POB1/REPS2 plays a regula... | MODIFY | Summary: Refine REPS2 recognition to proline-rich region binding. Reason: GOA identifies REPS2/Q8NFH8. The abstract maps SH3-recognized motifs within its central proline-rich region using peptide arrays, mutagenesis and co-immunoprecipitation. The proposed molecular term describes the region recognized by BIN1; it does not assign REPS2 or Grb2 functions to BIN1. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:18647389 binding motifs for 14-3-3 and for the SH3 of the proteins Amphiphysin II and Grb2 |
| GO:0005515 protein binding | IPI PMID:18985028 Hepatitis C virus infection protein network. | MODIFY | Summary: Refine the curated NS5A association using independent motif evidence. Reason: GOA supplies processed NS5A/Q9WMX2-PRO_0000037551. The original study is a viral-host interaction survey; its exact BIN1 pair-level dataset was not independently inspected. The same NS5A-BIN1 interaction is mechanistically corroborated by motif mapping in PMID:12604805 and PMID:16530520, supporting proline-rich region binding while keeping this source and its assay provenance unchanged. Proposed replacements: proline-rich region binding |
| GO:0005515 protein binding | IPI PMID:23917616 The myotubularin-amphiphysin 2 complex in membrane tubulatio... | MODIFY | Summary: Refine MTM1 binding to phosphatase binding. Reason: GOA identifies myotubularin/MTM1 Q13496. The complete abstract establishes binding in vitro and in skeletal muscle and shows that stimulation of BIN1-mediated tubulation depends on MTM1 binding and phosphoinositide phosphatase activity. Phosphatase binding describes the partner; protein phosphatase binding would incorrectly imply a protein substrate for this lipid phosphatase. Proposed replacements: phosphatase binding Supporting Evidence: PMID:23917616 MTM1 enhances BIN1-mediated membrane tubulation, depending on binding and phosphoinositide phosphatase activity |
| GO:0005515 protein binding | IPI PMID:24169621 Elucidating novel hepatitis C virus-host interactions using ... | MODIFY | Summary: Refine the curated NS5A association using independent motif evidence. Reason: GOA supplies processed NS5A/Q9WMX2-PRO_0000037551. The original study is a viral-host interaction survey; its exact BIN1 pair-level dataset was not independently inspected. The same NS5A-BIN1 interaction is mechanistically corroborated by motif mapping in PMID:12604805 and PMID:16530520, supporting proline-rich region binding while keeping this source and its assay provenance unchanged. Proposed replacements: proline-rich region binding |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | UNDECIDED | Summary: The HENA interaction pairs remain unresolved at source level. Reason: The two GOA partners are SNX4/O95219 and AMPH/P49418. The complete abstract describes a heterogeneous Alzheimer network, and a literal search of the cached full-text body finds no BIN1/amphiphysin occurrence. The underlying pair-level records and evidence grades were not recovered. SNX4 has independent support in PMID:12668730, but that does not adjudicate the combined HENA assertion; no removal or misattribution is inferred. |
| GO:0005515 protein binding | IPI PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei... | KEEP AS NON CORE | Summary: Retain the source-supported neuronal BIN1-RIN3 association as non-core. Reason: Selected PMID32552912 Results show BIN1-RIN3 co-immunoprecipitation in HEK293T cells and yeast two-hybrid interaction, corroborated by human IntAct pair records EBI-26520878 and EBI-26529583. The Methods specify a neuronal BIN1 isoform; its exact UniProt isoform accession was not recovered, so the source isoform field and all alternative products remain unchanged. PC12 and mouse-neuron recruitment experiments provide distinct cellular context. The selected Results leave an SH2/PRD contribution on RIN3 open and did not directly delete its PRD; they do not establish a mapped BIN1 recognition sequence. Retain the supported generic association as KEEP_AS_NON_CORE under the explicit CLINGEN_MENDELIAN project instruction, without assigning RIN3 GEF activity to BIN1 or generalizing the assay to every BIN1 isoform. Supporting Evidence: PMID:32552912 RIN3 directly interacts with BIN1 and CD2AP either simultaneously or separately |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The exact survey interaction evidence remains unadjudicated. Reason: The complete abstract describes BioPlex affinity-purification networks in 293T and HCT116 cells. GOA identifies AMPH/P49418 and BIN2/Q9UBW5. The original pair-level records, controls and evidence thresholds were not independently inspected, and the cached body contains no literal BIN1/amphiphysin mention. This uncertainty concerns the specific source assertion, not whether BIN1 generally binds proteins; it does not justify removal or a new mechanistic refinement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | UNDECIDED | Summary: The exact survey interaction evidence remains unadjudicated. Reason: The complete abstract describes OpenCell endogenous tagging, microscopy and mass-spectrometry mapping. GOA identifies AMPH/P49418 and RIN3/Q8TB24. The original pair-level records, controls and evidence thresholds were not independently inspected, and the cached body contains no literal BIN1/amphiphysin mention. This uncertainty concerns the specific source assertion, not whether BIN1 generally binds proteins; it does not justify removal or a new mechanistic refinement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | UNDECIDED | Summary: The exact survey interaction evidence remains unadjudicated. Reason: The complete abstract describes multimodal mapping in U2OS cells. GOA identifies AMPH/P49418. The original pair-level records, controls and evidence thresholds were not independently inspected, and the cached body contains no literal BIN1/amphiphysin mention. This uncertainty concerns the specific source assertion, not whether BIN1 generally binds proteins; it does not justify removal or a new mechanistic refinement. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:23917616 The myotubularin-amphiphysin 2 complex in membrane tubulatio... | KEEP AS NON CORE | Summary: BIN1 self-association is compatible with BAR assembly. Reason: GOA identifies BIN1 itself as the partner. The source abstract focuses on MTM1 binding and does not expose the self-association assay. The membrane-bound oligomerization experiments in PMID:24755653 independently support BIN1 self-assembly. Retain this binding annotation as non-core rather than mistake self-association for evidence of a separate catalytic activity. |
| GO:0042802 identical protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | UNDECIDED | Summary: The HENA self-interaction record needs pair-level inspection. Reason: GOA identifies BIN1/O00499 as its own partner. Self-association is biologically plausible and independently supported in membrane-remodeling experiments, but the HENA abstract and cached body do not expose this exact record. Retain uncertainty about that source rather than infer a false annotation from absence in the narrative. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: Retain synaptic vesicle as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0030018 Z disc | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred Z disc annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0031674 I band | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred I band annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0033268 node of Ranvier | IEA GO_REF:0000107 | ACCEPT | Summary: Retain node of Ranvier as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0043194 axon initial segment | IEA GO_REF:0000107 | ACCEPT | Summary: Retain axon initial segment as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0043196 varicosity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred varicosity annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0043679 axon terminus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred axon terminus annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0044300 cerebellar mossy fiber | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred cerebellar mossy fiber annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred protein-containing complex binding annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0045807 positive regulation of endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Retain positive regulation of endocytosis as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0048488 synaptic vesicle endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Retain synaptic vesicle endocytosis as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0051020 GTPase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain GTPase binding as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0098850 extrinsic component of synaptic vesicle membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Retain extrinsic component of synaptic vesicle membrane as part of BIN1 membrane-associated biology. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. The annotation is consistent with membrane remodeling and endocytic partner recruitment. Broad biological corroboration comes from the separately cited membrane/tubulation and dynamin studies; the precise ortholog experiment was not independently re-curated. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the transferred glutamatergic synapse annotation as a contextual feature. Reason: The cached GOA provenance is ortholog transfer from UniProtKB:O08839|ensembl:ENSRNOP00000017573. This specialized location or association is compatible with tissue-specific BIN1 organization but is not needed to define its principal membrane-remodeling activity. The original donor experiment was not re-inspected; no new human assay or isoform equivalence is claimed. Supporting Evidence: GO_REF:0000107 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization is consistent with a peripheral membrane adaptor. Reason: Retain the curated immunofluorescence localization. Cytosolic BIN1 is independently observed in the selected human-brain fractionation Results of PMID:25051234, alongside membrane and cytoskeletal fractions; this does not imply exclusive cytosolic residence. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:10412034 Induction of apoptosis and differentiation in neuroblastoma ... | KEEP AS NON CORE | Summary: MYC-associated transcriptional repression is a contextual regulatory role. Reason: The complete abstract describes inhibition of MYC transactivation and cell-state-dependent growth, differentiation and apoptotic responses after BIN1 overexpression. Retain the annotation outside the membrane-remodeling core; do not turn overexpression effects into an obligatory response of every isoform. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:8782822 BIN1 is a novel MYC-interacting protein with features of a t... | KEEP AS NON CORE | Summary: Retain the original context-dependent nuclear localization. Reason: The original MYC paper supplies the curated nuclear assertion. The complete abstract does not expose its localization experiment, while PMID:9182667 explicitly discusses that earlier HepG2 observation and reports predominantly cytosolic localization in its own conditions. This is a contextual difference, not sufficient evidence to remove the original annotation. |
| GO:0010564 regulation of cell cycle process | IDA PMID:8782822 BIN1 is a novel MYC-interacting protein with features of a t... | KEEP AS NON CORE | Summary: Cell-cycle regulation is retained in the MYC/tumor-cell context. Reason: The original abstract reports inhibition of MYC-driven transformation and growth inhibition following restoration of BIN1 in deficient tumor cells. These observations support a contextual growth-regulatory role, separate from the core membrane-shaping machinery. Supporting Evidence: PMID:8782822 BIN1 inhibited malignant cell transformation by MYC |
| GO:0090571 RNA polymerase II transcription repressor complex | IPI PMID:15992821 A structure-based model of the c-Myc/Bin1 protein interactio... | UNDECIDED | Summary: Membership of a transcription-repressor complex needs direct source confirmation. Reason: The complete abstract establishes a structural BIN1-MYC interaction and regulation by splicing and MYC phosphorylation. It does not resolve the composition or transcription-repressor status of the annotated complex, and full text was not inspected. Binding a transcription factor is not by itself proof of membership of this specific complex; retain uncertainty rather than remove a curator assertion. Supporting Evidence: PMID:15992821 C-terminal SH3 domain of Bin1 as the primary structure determinants of their interaction |
| GO:0005737 cytoplasm | EXP PMID:9182667 Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rv... | ACCEPT | Summary: Cytoplasmic localization is directly supported in the reported transfection systems. Reason: Selected Results in PMID:9182667 report predominantly cytosolic localization of amphiphysin II constructs in COS-7 and HepG2 cells, alongside tissue-specific membrane-cortical localization. Preserve the source EXP code and avoid converting rat-tissue observations into human-tissue assays. Supporting Evidence: |
| GO:0005768 endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Retain endosomal localization transferred from an ortholog. Reason: The source is a curated ISS transfer. Independent selected PMID:32552912 Results show recruitment of endogenous BIN1 to RIN3-positive endosomal structures in PC12 cells and mouse neurons. Those experiments corroborate the compartment while retaining the human annotation as an inference. |
| GO:0008289 lipid binding | EXP PMID:18658220 Structure and dynamics of helix-0 of the N-BAR domain in lip... | ACCEPT | Summary: Lipid binding is directly supported by the human BIN1 N-BAR study. Reason: The complete abstract reports the structure and behavior of human BIN1 helix-0 in lipid-mimetic environments and reduced liposome tubulation following helix deletion. The lipid-binding assertion remains correct; the integrated core separately describes the membrane-bending activity demonstrated by these and subsequent experiments. Supporting Evidence: |
| GO:0060988 lipid tube assembly | IDA PMID:18658220 Structure and dynamics of helix-0 of the N-BAR domain in lip... | ACCEPT | Summary: BIN1 contributes directly to lipid-tube assembly. Reason: The human N-BAR study reports liposome tubulation and a requirement for helix-0 for efficient deformation. BIN1 performs membrane shaping itself, rather than merely being a transported cargo; the process is therefore appropriate. Selected PMID:24755653 reconstitution provides independent corroboration. |
| GO:1901380 negative regulation of potassium ion transmembrane transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the ortholog-transferred potassium flux effect as contextual physiology. Reason: GOA records a curated transfer from mouse BIN1/O08539. Membrane microdomain organization can affect ion-channel trafficking and local diffusion without making BIN1 an ion channel. The donor experiment underlying this precise directional phenotype was not re-inspected; retain the curator inference outside the compact molecular core. Supporting Evidence: GO_REF:0000024 |
| GO:1903946 negative regulation of ventricular cardiac muscle cell action potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the ortholog-transferred ventricular action potentials effect as contextual physiology. Reason: GOA records a curated transfer from mouse BIN1/O08539. Membrane microdomain organization can affect ion-channel trafficking and local diffusion without making BIN1 an ion channel. The donor experiment underlying this precise directional phenotype was not re-inspected; retain the curator inference outside the compact molecular core. Supporting Evidence: GO_REF:0000024 |
| GO:0030838 positive regulation of actin filament polymerization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Actin polymerization regulation is retained as a contextual cytoskeletal effect. Reason: The source is a curated mouse BIN1/O08539 transfer. BIN1 has independent actin and cytoskeletal interactions, but the original experiment establishing the direction of polymerization regulation was not inspected. This annotation does not make BIN1 actin itself or assign it nucleation-complex catalytic activity. |
| GO:0086091 regulation of heart rate by cardiac conduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the ortholog-transferred cardiac conduction and heart rate effect as contextual physiology. Reason: GOA records a curated transfer from mouse BIN1/O08539. Membrane microdomain organization can affect ion-channel trafficking and local diffusion without making BIN1 an ion channel. The donor experiment underlying this precise directional phenotype was not re-inspected; retain the curator inference outside the compact molecular core. Supporting Evidence: GO_REF:0000024 |
| GO:1904878 negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the ortholog-transferred high-voltage-gated calcium-channel flux effect as contextual physiology. Reason: GOA records a curated transfer from mouse BIN1/O08539. Membrane microdomain organization can affect ion-channel trafficking and local diffusion without making BIN1 an ion channel. The donor experiment underlying this precise directional phenotype was not re-inspected; retain the curator inference outside the compact molecular core. Supporting Evidence: GO_REF:0000024 |
| GO:0030424 axon | ISS PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei... | ACCEPT | Summary: Retain the transferred axon localization. Reason: Selected source Results show endogenous BIN1 in RIN3-positive puncta in axons and dendrites of mouse embryonic neurons and in enlarged vesicular structures in PC12 cells. This supports the localization in the experimental organisms while preserving the human ISS assertion and its original qualifier. Supporting Evidence: |
| GO:0030425 dendrite | ISS PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei... | ACCEPT | Summary: Retain the transferred dendrite localization. Reason: Selected source Results show endogenous BIN1 in RIN3-positive puncta in axons and dendrites of mouse embryonic neurons and in enlarged vesicular structures in PC12 cells. This supports the localization in the experimental organisms while preserving the human ISS assertion and its original qualifier. Supporting Evidence: |
| GO:0031982 vesicle | ISS PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei... | ACCEPT | Summary: Retain the transferred vesicle localization. Reason: Selected source Results show endogenous BIN1 in RIN3-positive puncta in axons and dendrites of mouse embryonic neurons and in enlarged vesicular structures in PC12 cells. This supports the localization in the experimental organisms while preserving the human ISS assertion and its original qualifier. Supporting Evidence: |
| GO:0019828 aspartic-type endopeptidase inhibitor activity | IMP PMID:27179792 BIN1 regulates BACE1 intracellular trafficking and amyloid-Ξ²... | UNDECIDED | Summary: BACE1 abundance and trafficking effects do not settle the inhibitor-activity assertion. Reason: GO:0019828 requires binding to and reduction of aspartic-type endopeptidase activity. The complete abstract positively establishes an abundance/trafficking mechanism: BIN1 depletion impairs BACE1 endosomal trafficking and lysosomal degradation, increasing BACE1 levels and amyloid-beta production. That mechanism alone does not establish molecular enzyme inhibition. The normal cache is abstract-only, and the prior publisher/article-PDF inspection exposed no full Results or inhibition assays. Neither this mechanistic summary nor the absence of a recognized inhibitory domain establishes that the full paper lacks additional relevant experiments. The experimental IMP assertion therefore remains UNDECIDED pending those assays; trafficking is already represented separately by GO:0008333. This supersedes the confident cross-aspect MODIFY endorsed in the June notes, which relied partly on the provider summary rather than the inaccessible full experiment. Supporting Evidence: PMID:27179792 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation |
| GO:1902430 negative regulation of amyloid-beta formation | IMP PMID:27179792 BIN1 regulates BACE1 intracellular trafficking and amyloid-Ξ²... | KEEP AS NON CORE | Summary: Retain the BACE1-dependent effect on amyloid-beta formation. Reason: The complete abstract links BIN1 depletion to impaired BACE1 trafficking/degradation, increased BACE1 levels and increased amyloid-beta production. This is a supported cargo-specific outcome of trafficking, not the principal molecular activity of BIN1. Supporting Evidence: |
| GO:0008333 endosome to lysosome transport | IMP PMID:27179792 BIN1 regulates BACE1 intracellular trafficking and amyloid-Ξ²... | ACCEPT | Summary: BIN1-dependent endosomal delivery to lysosomes is a trafficking function. Reason: The complete abstract identifies impaired endosomal trafficking and reduced lysosomal BACE1 degradation after BIN1 depletion. Retain the existing process as a membrane-trafficking contribution rather than demote it solely because the chosen cargo is disease related. This does not mean BIN1 performs BACE1 proteolysis or lysosomal catalysis. Supporting Evidence: |
| GO:0048156 tau protein binding | NAS PMID:28386764 Roles of tau protein in health and disease. | KEEP AS NON CORE | Summary: Retain the review-based tau-binding assertion with direct-paper corroboration. Reason: The source is a tau review rather than a new binding assay. Its selected proline-rich-domain discussion names BIN1 among SH3-containing tau partners. Direct biochemical support is available in PMID:23399914 and PMID:28755476; those sources support the association without making every tau-pathology outcome a BIN1 core function. |
| GO:0005515 protein binding | IPI PMID:17676042 Mutations in amphiphysin 2 (BIN1) disrupt interaction with d... | MODIFY | Summary: Refine DNM2 recognition to GTPase binding. Reason: The raw GOA partner is DNM2/P50570. The complete abstract reports that a pathogenic BIN1 SH3 truncation prevents DNM2 interaction and recruitment to membrane tubules. DNM2 is the GTPase partner, not a small monomeric GTPase; the proposed term does not assign GTP hydrolysis to BIN1. Proposed replacements: GTPase binding Supporting Evidence: PMID:17676042 interaction with DNM2 and its recruitment to the membrane tubules |
| GO:0033292 T-tubule organization | IDA PMID:24755653 Mutations in BIN1 associated with centronuclear myopathy dis... | ACCEPT | Summary: BIN1 membrane shaping supports T-tubule organization. Reason: Selected Results compare BIN1 N-BAR constructs in mouse C2C12 myoblasts and purified-domain liposome assays. Wild-type constructs generate membrane tubules; disease variants alter curvature generation and membrane assembly in condition-dependent ways. This mechanistically supports the T-tubule process, while the paper explicitly distinguishes domain assays from the complexity of mature muscle T-tubule biogenesis. Supporting Evidence: |
| GO:0030315 T-tubule | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the ortholog-transferred T-tubule annotation. Reason: BIN1 membrane remodeling is central to muscle T-tubule organization. The human annotation remains a curated ISS transfer, independently consistent with the skeletal-muscle localization in PMID:9182667 and disease/biophysical studies. Isoform context matters; this is not a claim that every splice product organizes muscle T-tubules. |
| GO:0033292 T-tubule organization | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the ortholog-transferred T-tubule annotation. Reason: BIN1 membrane remodeling is central to muscle T-tubule organization. The human annotation remains a curated ISS transfer, independently consistent with the skeletal-muscle localization in PMID:9182667 and disease/biophysical studies. Isoform context matters; this is not a claim that every splice product organizes muscle T-tubules. |
| GO:0002020 protease binding | IPI PMID:27179792 BIN1 regulates BACE1 intracellular trafficking and amyloid-Ξ²... | KEEP AS NON CORE | Summary: Retain BACE1 binding as a specific cargo interaction. Reason: The original IPI annotation and normal UniProt record identify a BAR-mediated BACE1 association. The complete source abstract establishes trafficking/degradation consequences, but the binding assay itself was not inspected. Preserve this curator-grounded association as a cargo interaction without equating protease binding with inhibition or protease activity. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | UNDECIDED | Summary: The nuclear fraction result requires figure-level confirmation. Reason: Selected source Results emphasize cytosolic, membrane and cytoskeleton/insoluble BIN1.1 fractions; the full-text record is available, but the fractionation figure and quantitative nuclear signal were not inspected. The prior generic nuclear/tumor-suppressor explanation does not establish this particular human-brain IDA result. Keep the assertion unresolved rather than remove it. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | ACCEPT | Summary: Human-brain fractionation supports cytoplasmic BIN1. Reason: Selected Results place most BIN1.1 in cytosolic and membrane fractions and also detect it in the cytoskeleton/insoluble fraction. These data support a cytoplasmic pool without implying uniform distribution across tissues or isoforms. Supporting Evidence: |
| GO:0005856 cytoskeleton | IDA PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | ACCEPT | Summary: Retain the limited cytoskeletal colocalization assertion. Reason: Selected human-brain fractionation Results detect BIN1.1 in a cytoskeleton/insoluble fraction, with Tau/p-Tau enrichment in Alzheimer samples. The source qualifier is colocalizes_with and is retained: this fractionation result alone is not recast as direct actin binding or obligatory incorporation into a cytoskeletal polymer. Supporting Evidence: PMID:25051234 a significant amount of BIN1.1 was found in the cytoskeleton/insoluble fraction |
| GO:0006897 endocytosis | TAS PMID:23399914 Increased expression of BIN1 mediates Alzheimer genetic risk... | ACCEPT | Summary: Retain the author-statement endocytosis annotation. Reason: The source treats BIN1 as an endocytic membrane adaptor, while its main experiments address tau or clusterin. Retain the TAS provenance rather than describe these as new endocytosis assays. Independent amphiphysin/SNX4 and dynamin evidence corroborates the established role. |
| GO:0006897 endocytosis | TAS PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | ACCEPT | Summary: Retain the author-statement endocytosis annotation. Reason: The source treats BIN1 as an endocytic membrane adaptor, while its main experiments address tau or clusterin. Retain the TAS provenance rather than describe these as new endocytosis assays. Independent amphiphysin/SNX4 and dynamin evidence corroborates the established role. |
| GO:0007010 cytoskeleton organization | TAS PMID:23399914 Increased expression of BIN1 mediates Alzheimer genetic risk... | ACCEPT | Summary: Cytoskeletal organization is consistent with direct BIN1 structural interactions. Reason: The original TAS statement is contextual in a tau study. The later PMID:26506308 abstract independently reports BIN1 links to nesprin, actin and CLIP170 and a direct role in nuclear positioning. This supports cytoskeletal organization without attributing all tau-mediated neurotoxicity to BIN1. |
| GO:0016020 membrane | IDA PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | ACCEPT | Summary: Human-brain fractionation supports membrane-associated BIN1. Reason: The selected source Results detect BIN1.1 in membrane as well as cytosolic and cytoskeleton/insoluble fractions. A membrane-associated pool is consistent with BAR lipid binding; the data do not make BIN1 an integral membrane protein. Supporting Evidence: |
| GO:0016020 membrane | TAS PMID:28755476 Regulation of the interaction between the neuronal BIN1 isof... | ACCEPT | Summary: Retain the membrane association stated in the isoform study. Reason: The paper focuses on conformational regulation of BIN1 SH3 and tau binding. Membrane association is retained as TAS, corroborated by the direct N-BAR membrane-remodeling study, rather than presenting this NMR study as a new membrane-localization experiment. |
| GO:0030276 clathrin binding | TAS PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | ACCEPT | Summary: Retain clathrin recognition in the relevant splice-isoform context. Reason: The source introduction and selected Results describe brain isoforms containing the clathrin/AP2-binding region. Normal UniProt distinguishes CLTC-binding IIA from several nonbinding splice forms. Keep the gene-level TAS assertion without claiming identical CLAP composition or binding for all eleven products. Supporting Evidence: |
| GO:0048156 tau protein binding | IPI PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | KEEP AS NON CORE | Summary: BIN1-tau association is supported in transfected cells and human brain. Reason: Selected Results show co-immunoprecipitation with Tau for all ten tested human BIN1 constructs and increased BIN1.1/Tau/clusterin association in Alzheimer brain lysates. These specific experiments support the binding annotation; they do not establish a common physiological outcome for every isoform. Supporting Evidence: |
| GO:0051087 protein-folding chaperone binding | IPI PMID:25051234 Intracellular clusterin interacts with brain isoforms of the... | KEEP AS NON CORE | Summary: Retain intracellular clusterin binding as an isoform-dependent interaction. Reason: GOA identifies clusterin/P10909. Selected Results map iCLU association to coiled-coil-containing BIN1 isoforms 1-3 and show associations in human-brain lysates. This is a partner-class annotation, not a demonstration that BIN1 acts as a chaperone or that the interacting intracellular CLU construct folds a substrate in this assay. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in F- and N- BAR domain proteins bind the clathrin-coated pit. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in SNX9 recruits components of the actin polymerizing machinery. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in BAR domain proteins recruit dynamin. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in SYNJ hydrolyze PI(4,5)P2 to PI(4)P. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in Endophilins recruit synaptojanins to the clathrin-coated pit. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in HSPA8-mediated ATP hydrolysis promotes vesicle uncoating. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in Clathrin recruits auxilins to the clathrin-coated vesicle. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in Dynamin-mediated GTP hydrolysis promotes vesicle scission. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in Dissociation of clathrin-associated proteins. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in Dissociation of AAK1 and dephosphorylation of AP-2 mu2. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: Retain the cytosolic compartment assigned in the Reactome event. Reason: This TAS row assigns cytosol; it does not assign BIN1 the catalytic activity in RAB5 and GAPVD1 bind AP-2. The cached event summary describes the broader clathrin pathway and does not independently resolve a BIN1-specific experiment. Cytosolic BIN1 is separately supported by human-brain fractionation and transfection studies. |
| GO:0005515 protein binding | IPI PMID:26506308 Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by ... | MODIFY | Summary: Refine the combined CLIP170/nesprin interactions to cytoskeletal protein binding. Reason: GOA contains CLIP170/P30622 and nesprin-2/Q8WXH0 partners. The complete abstract explicitly reports BIN1 associations with nesprin, actin and CLIP170 in nematode and mammalian systems and links these contacts to nuclear positioning. Cytoskeletal protein binding covers the two recorded partners; actin filament binding would not describe those two source interactions. This source object combines a microtubule regulator with a nuclear-envelope/cytoskeletal linker; the narrower regulatory-partner term established for CLIP170 alone is not asserted across both partners. Proposed replacements: cytoskeletal protein binding Supporting Evidence: PMID:26506308 binds to nesprin and actin PMID:26506308 microtubule-bindingΒ protein CLIP170 |
| GO:0006997 nucleus organization | IMP PMID:26506308 Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by ... | ACCEPT | Summary: Nuclear organization reflects a direct cytoskeletal linkage function. Reason: The complete abstract reports altered nuclear position and shape in worm, mammalian-cell and patient-muscle contexts, interaction with nesprin/actin/CLIP170, and rescue by a microtubule-to-nuclear-envelope fusion in worms. This is a mechanistic structural contribution, not the MYC/apoptosis phenotype described by the prior reason. The rescue is not called a human experiment. Supporting Evidence: |
| GO:0051015 actin filament binding | IDA PMID:26506308 Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by ... | ACCEPT | Summary: Retain the experimentally curated actin-filament binding activity. Reason: The complete abstract reports AMPH-1/BIN1 association with actin together with nesprin and CLIP170. Preserve the curated IDA specificity while acknowledging that the detailed actin-binding assay was not inspected. Normal UniProt independently records BAR-mediated F-actin binding; binding and structural coupling are distinct from actin catalytic activity. Supporting Evidence: |
| GO:0016020 membrane | IDA PMID:16530520 The SH3 binding motif of HCV [corrected] NS5A protein intera... | ACCEPT | Summary: Retain membrane localization in the NS5A interaction context. Reason: The source reports co-immunoprecipitation and confocal analysis of BIN1 with NS5A. The complete abstract does not expose the precise compartment image, but the existing membrane assertion is independently consistent with direct BIN1 membrane-binding and fractionation experiments. Retain it without turning a viral-cell assay into a universal localization. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:16530520 The SH3 binding motif of HCV [corrected] NS5A protein intera... | KEEP AS NON CORE | Summary: BIN1-induced apoptosis is retained in the hepatoma overexpression context. Reason: The complete abstract reports apoptosis after adeno-BIN1 expression in BIN1-deficient HepG2 cells and inhibition by wild-type NS5A, but not its SH3-binding-motif mutant. This is a supported contextual effect, distinct from the membrane-remodeling core. Supporting Evidence: |
| GO:0070063 RNA polymerase binding | IPI PMID:16530520 The SH3 binding motif of HCV [corrected] NS5A protein intera... | UNDECIDED | Summary: The RNA-polymerase partner interpretation needs source-level resolution. Reason: GO:0070063 denotes binding an RNA polymerase molecule or complex. The source partner set is P27958-PRO_0000037576 and Q9WMX2-PRO_0000037551. UniProt directly identifies P27958-PRO_0000037576 as NS5A (1973-2420); its RNA-directed RNA polymerase is the separate NS5B chain PRO_0000037577 (2421-3011). The complete PMID:16530520 abstract reports NS5A PxxP-motif binding, so treating that contact as direct NS5B binding would be incorrect. The exact Q9WMX2 feature was not independently retrievable, and the full paper and any polymerase-complex association assay remain uninspected. UNDECIDED retains that source-level uncertainty without alleging curator misattribution. NS5A proline-rich recognition is independently represented by the other IPI row. Supporting Evidence: |
| GO:0030018 Z disc | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the transferred muscle-band localization as contextual. Reason: This ISS assertion concerns a specialized sarcomeric compartment. T-tubule organization is firmly supported, but localization near muscle bands is not interchangeable with incorporation into every sarcomeric structure. The exact donor experiment was not re-inspected; retain its scoped assertion outside the compact core-location list. Supporting Evidence: GO_REF:0000024 |
| GO:0031674 I band | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the transferred muscle-band localization as contextual. Reason: This ISS assertion concerns a specialized sarcomeric compartment. T-tubule organization is firmly supported, but localization near muscle bands is not interchangeable with incorporation into every sarcomeric structure. The exact donor experiment was not re-inspected; retain its scoped assertion outside the compact core-location list. Supporting Evidence: GO_REF:0000024 |
| GO:0033268 node of Ranvier | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the transferred axonal-domain localization. Reason: The source is curated ISS. Selected PMID:9182667 rat-brain Results demonstrate cortical enrichment at axon initial segments and nodes of Ranvier, consistent with membrane/cytoskeletal organization at these specialized domains. This corroboration preserves the human inference and does not assert an assay on human brain. |
| GO:0043194 axon initial segment | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the transferred axonal-domain localization. Reason: The source is curated ISS. Selected PMID:9182667 rat-brain Results demonstrate cortical enrichment at axon initial segments and nodes of Ranvier, consistent with membrane/cytoskeletal organization at these specialized domains. This corroboration preserves the human inference and does not assert an assay on human brain. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:10412034 Induction of apoptosis and differentiation in neuroblastoma ... | KEEP AS NON CORE | Summary: Retain the cell-state-dependent apoptosis response. Reason: The complete abstract reports increased apoptosis after BIN1 overexpression in undifferentiated neuroblastoma and astrocytoma cells, together with reduced growth and a larger G0/G1 population. That positive perturbation result supports the existing apoptosis annotation as a cell-state-dependent, non-core effect. Already committed cells instead showed further differentiation without detectable apoptosis; the annotation does not imply that BIN1 induces apoptosis in every cell state. Supporting Evidence: |
| GO:0048711 positive regulation of astrocyte differentiation | IMP PMID:10412034 Induction of apoptosis and differentiation in neuroblastoma ... | KEEP AS NON CORE | Summary: Retain the cell-state-dependent astrocyte differentiation response. Reason: The positive result is further progression toward differentiated phenotypes after BIN1 overproduction in neuroblastoma and astrocytoma cells already committed to neuronal and astrocyte differentiation, respectively. Increasing the extent of differentiation in that context is compatible with GO:0048711; the term does not require initiating differentiation in uncommitted cells. The same abstract separately reports no marker induction in undifferentiated cells, where apoptosis predominated. Retain the existing IMP assertion as non-core with this ectopic-expression and transformed-cell scope, without extending it to normal astrocyte development or every BIN1 isoform. Supporting Evidence: PMID:10412034 further induction towards more differentiated phenotypes |
| GO:0005515 protein binding | IPI PMID:19004523 The membrane-tubulating potential of amphiphysin 2/BIN1 is d... | MODIFY | Summary: Refine CLIP170 recognition to cytoskeletal regulatory protein binding. Reason: GOA identifies CLIP170/P30622. The complete abstract maps association to the BIN1 N-terminal/BAR region and an internal CLIP170 coiled coil, with pull-down and endogenous HeLa co-immunoprecipitation. CLIP170 regulates microtubule stability and its depletion reduces BIN1-positive tubules, supporting recognition of a cytoskeletal regulator. This is not direct tubulin binding. Because this source object contains CLIP170 alone and explicitly establishes its microtubule-regulatory role, GO:0005519 is available here; the combined CLIP170/nesprin-2 assertion from PMID:26506308 uses GO:0008092 to cover both recorded partners. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: PMID:19004523 the N-terminal part of amphiphysin 2 (mostly the BAR domain) and an internal coiled-coil region of CLIP-170 |
| GO:0060987 lipid tube | IMP PMID:19004523 The membrane-tubulating potential of amphiphysin 2/BIN1 is d... | ACCEPT | Summary: Retain BIN1 as a component of the induced lipid-tube structures. Reason: The source describes intracellular BIN1-positive tubules in HeLa cells and dependence on microtubules and CLIP170. Preserve the part_of qualifier; this annotation does not equate these experimental tubules with muscle T-tubules. Supporting Evidence: |
| GO:0060988 lipid tube assembly | IMP PMID:19004523 The membrane-tubulating potential of amphiphysin 2/BIN1 is d... | ACCEPT | Summary: BIN1 directly participates in lipid-tube assembly with cytoskeletal support. Reason: The source combines an intrinsic membrane-tubulation function with CLIP170-dependent interactions and perturbation of BIN1-positive tubules after microtubule depolymerization or CLIP170 depletion. BIN1 supplies the membrane-shaping component rather than simply reporting a distant phenotype. Supporting Evidence: |
| GO:0030424 axon | IDA PMID:23399914 Increased expression of BIN1 mediates Alzheimer genetic risk... | ACCEPT | Summary: Retain axonal localization in the neuronal BIN1 context. Reason: The original human annotation is supported by the curator-selected experiment. The selected paper sections independently show neuronal BIN1 cytoskeletal distribution and mouse synaptosomal recovery, but the particular axonal image was not inspected. Rat-brain axonal-domain localization in PMID:9182667 provides separate corroboration, not a replacement human IDA experiment. |
| GO:0045664 regulation of neuron differentiation | IMP PMID:10412034 Induction of apoptosis and differentiation in neuroblastoma ... | KEEP AS NON CORE | Summary: Retain the cell-state-dependent neuronal differentiation response. Reason: The complete abstract describes BIN1 overexpression in neuroblastoma and astrocytoma lines. Undifferentiated cells show growth inhibition and apoptosis without induction of differentiation markers; already committed cells instead progress toward differentiated phenotypes. Preserve that distinction rather than claim BIN1 universally induces differentiation or apoptosis. Supporting Evidence: |
| GO:0048156 tau protein binding | IPI PMID:23399914 Increased expression of BIN1 mediates Alzheimer genetic risk... | KEEP AS NON CORE | Summary: Direct BIN1-Tau interaction is supported. Reason: Selected Results include reciprocal cellular co-immunoprecipitation, GST pull-down with purified recombinant Tau, and endogenous mouse-brain synaptosomal co-immunoprecipitation. This is strong partner evidence; the unresolved relation to Alzheimer pathogenesis is not a reason to discount the binding itself. Supporting Evidence: PMID:23399914 The direct BIN1-Tau interaction was validated |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: Retain cytoplasmic localization of expressed BIN1. Reason: The GO_REF identifies curated fusion-protein localization in living cells. Independent transfection and human-brain fractionation studies support cytoplasmic pools while showing membrane and cytoskeletal association. The original image set was not re-inspected. |
| GO:0015629 actin cytoskeleton | TAS PMID:9182667 Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rv... | ACCEPT | Summary: Retain the actin-cytomatrix association stated in the localization study. Reason: Selected Results place amphiphysin II in cortical cytomatrix at rat axonal domains and around skeletal-muscle T-tubules, colocalizing with ankyrin3. The source is TAS and does not itself establish purified actin binding; that distinct molecular interaction is represented by PMID:26506308. |
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Download this section (compressed HTML)Q: Which full-paper assay or polymerase-complex interpretation supports GO:0070063 from PMID:16530520? The directly checked P27958 partner chain is NS5A, distinct from the NS5B polymerase; the exact Q9WMX2 processed-chain feature and original source-specific assay remain to be verified.
Q: Does PMID:27179792 demonstrate inhibition of BACE1 molecular activity beyond altered abundance and endosomal delivery?
Q: How should the 122 raw GOA assertions be reconciled with the 112 existing review objects so that collapsed partner sets are retained without changing source identity?
Q: Which human BIN1 splice products account for individual neuronal, sarcomeric and nuclear localizations, and how do those product identifiers map to the different numbering systems used in older papers?
Experiment: Compare expression-matched rescue with defined full-length human BIN1 splice products and BAR/SH3 perturbations in myotubes and neurons, measuring membrane tubulation, dynamin recruitment and cargo trafficking separately.
Hypothesis: Distinct BIN1 membrane-binding and partner-recruitment modules make separable contributions to membrane remodeling.
Experiment: Measure BACE1 activity at matched enzyme abundance alongside endosome-to-lysosome delivery and turnover after BIN1 perturbation; test whether the effects persist when trafficking is held constant.
Hypothesis: The effect of BIN1 on BACE1 output can arise from altered trafficking rather than reduced activity per BACE1 molecule.
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