| Protein partner | Domain of BIN1 involved in interaction | Cellular pathway/process | Functional consequence of interaction | Tissue/cell type specificity |
|---|---|---|---|---|
| Dynamin-2 (DNM2) | Primarily SH3 domain; BAR domain functionally cooperates by generating curved membranes | Clathrin-mediated endocytosis, vesicle scission, T-tubule biogenesis | BIN1 recruits DNM2 to curved membranes; this supports vesicle scission in endocytosis and contributes to T-tubule formation/remodeling. Loss of SH3-mediated recruitment is central to BIN1-related centronuclear myopathy (pqac-00000000, pqac-00000009) | Broadly relevant; especially skeletal muscle and cardiac muscle, also endocytic membranes in other cells (pqac-00000000, pqac-00000013) |
| Tau (MAPT) | SH3 domain binds Tau proline-rich motif | Alzheimer-related tau biology, tau aggregation/propagation | Direct BIN1-Tau binding is modulated by Tau phosphorylation; BIN1 cleavage fragment BIN1(1-277) can bind Tau and accelerate aggregation while enhancing clathrin-mediated endocytosis-dependent propagation (pqac-00000008, pqac-00000005) | Neurons/brain; especially relevant to Alzheimer’s disease (pqac-00000005, pqac-00000003) |
| c-Myc / N-Myc | Myc-binding domain (MBD; exons 17-18) | Nuclear signaling, cell-cycle control, tumor suppression, apoptosis | BIN1 binds Myc and suppresses Myc-driven transcriptional and transforming activity; supports Myc-dependent apoptosis and broader tumor suppressor functions (pqac-00000007, pqac-00000013) | Nuclear isoforms in proliferative contexts; cancer-relevant tissues, and some cardiac/brain cell contexts with nuclear BIN1 isoforms (pqac-00000007, pqac-00000009) |
| Clathrin | CLAP domain (especially exons 14-15); neuronal isoforms may be particularly relevant | Clathrin-mediated endocytosis, vesicle biogenesis | BIN1 helps assemble clathrin-coated pits/vesicles and participates in membrane budding and trafficking from plasma membrane, Golgi, and endosomes (pqac-00000007, pqac-00000013) | Strongly established in neuronal/brain isoforms; likely also relevant in other tissues with CLAP-containing isoforms (pqac-00000002, pqac-00000013) |
| AP2 (Adaptor protein 2) | CLAP domain, especially exon 13 | Clathrin-mediated endocytosis and membrane trafficking | BIN1 association with AP2 helps coordinate endocytic complex assembly and cargo internalization at the plasma membrane (pqac-00000007, pqac-00000013) | Best established in neuronal/endocytic contexts; potentially relevant in cardiac isoforms containing exon 13 (pqac-00000007) |
| N-WASP | SH3 domain | Actin remodeling, membrane-cytoskeleton coupling, directed trafficking | BIN1-N-WASP interaction promotes ARP2/3-mediated actin polymerization and helps anchor actin to BIN1-associated membranes, supporting tubulation and membrane organization (pqac-00000009, pqac-00000011) | Neuronal and muscle contexts; implicated in t-tubule anchoring and membrane remodeling (pqac-00000011) |
| CaV1.2 (L-type calcium channel) | Not mapped to a single motif with the same precision as SH3 ligands; interaction/functionally linked to BAR-dependent membrane platforms and BIN1 scaffolding | Excitation-contraction coupling, targeted ion-channel trafficking | BIN1 colocalizes and co-immunoprecipitates with CaV1.2, promotes microtubule-dependent delivery to T-tubules, and supports channel clustering at dyads (pqac-00000011, pqac-00000013) | Cardiac myocytes; t-tubule sarcolemma (pqac-00000011, pqac-00000014) |
| RyR2 (ryanodine receptor 2) | Precise binding interface not yet clearly defined; likely scaffolded indirectly within BIN1-organized dyads | Excitation-contraction coupling, dyad organization | BIN1 supports RyR2 localization to dyads and proper junctional organization; BIN1 loss disrupts RyR2 positioning and calcium release synchrony (pqac-00000011, pqac-00000013) | Cardiac myocytes (pqac-00000011, pqac-00000014) |
| CLIP-170 | BAR domain | Microtubule anchoring, directed trafficking, membrane remodeling | BIN1-BAR interaction with CLIP-170 anchors microtubules to membrane tubules, enabling targeted delivery of cargo such as CaV1.2 to T-tubules (pqac-00000006, pqac-00000011) | Cardiac myocytes and cultured cells; likely broader relevance in membrane-directed trafficking (pqac-00000011, pqac-00000013) |
| MTM1 (myotubularin 1) | BAR and SH3 domains; interaction strongly influenced by PI domain-dependent conformation | Phosphoinositide-regulated membrane remodeling, T-tubule growth | MTM1 cooperates with BIN1 to promote elongated tubules in muscle; interaction is favored when BIN1 adopts an open conformation and links phosphoinositide homeostasis to membrane tubulation (pqac-00000012) | Strongly established in skeletal muscle; direct interaction less clear for exon 11-lacking cardiac isoforms, though MTM1 still influences cardiac t-tubule growth (pqac-00000012) |
| RIN2 | Specific BIN1 interaction interface not yet fully resolved in cited source | Early endosome targeting, Rab5-associated endosomal trafficking | RIN2 recruits BIN1 to RAB5-positive early endosomes, identifying a neuron-specific endosomal localization mechanism linked to Alzheimer-relevant trafficking pathways (pqac-00000010) | Human excitatory neurons / neuron-specific interactome context (pqac-00000010) |


*Table: This table summarizes major BIN1 protein interaction partners, the BIN1 domains involved, and the pathways they influence. It is useful for connecting BIN1’s membrane-remodeling scaffold function to tissue-specific roles in endocytosis, muscle excitation-contraction coupling, and Alzheimer’s disease biology.*