| Domain name | Exons encoding | Structural features | Primary molecular function | Key binding partners/substrates | Regulatory mechanisms |
|---|---|---|---|---|---|
| BAR domain | Exons 1–10 | N-terminal N-BAR; coiled-coil of three α-helices; positively charged concave membrane-binding surface; N-terminal amphipathic helix-0 inserts into bilayer; forms banana-shaped symmetric homodimers that can generate vesicles/tubules of ~220 Å radius (pqac-00000002, pqac-00000006) | Senses and generates membrane curvature; drives membrane tubulation/remodeling; anchors cytoskeletal delivery tracks at curved membranes; foundational structural scaffold for t-tubules, endocytic membranes, and other membrane microdomains (pqac-00000000, pqac-00000006, pqac-00000011) | Acidic phospholipids including PI(4,5)P2 and other phosphoinositides; CLIP-170; indirectly coordinates DNM2 recruitment through overall BIN1 architecture; membrane tubules associated with CaV1.2 delivery platforms (pqac-00000006, pqac-00000011, pqac-00000012) | Membrane binding is highly sensitive to lipid composition, especially PI(4,5)P2 and cholesterol; Lys164/Lys165/Lys166 in the BAR region are important for phospholipid anchoring; exon 7 within the BAR region modulates targeting specificity and may affect dynamin interaction (pqac-00000006, pqac-00000011) |
| PI-binding domain | Exon 11 | Phosphoinositide-binding segment adjacent to BAR domain; present in selected muscle-enriched and some cardiac/neuronal isoforms; can contact the SH3 domain to form a closed conformation (pqac-00000002, pqac-00000006) | Enhances membrane targeting specificity for PI(4,5)P2-rich membranes; augments curvature sensing/generation; helps localize active BIN1 to tubulating membrane domains such as T-tubules (pqac-00000006) | PI(4,5)P2; intramolecular interaction with SH3 domain; MTM1/myotubularin binding depends strongly on PI-domain-containing configurations in skeletal-muscle contexts (pqac-00000006, pqac-00000012) | Mediates autoinhibition by binding SH3; PI(4,5)P2 binding releases the closed state and activates membrane-sculpting function; SH3 engagement by proline-rich partners can also relieve autoinhibition (pqac-00000006, pqac-00000012) |
| PS linker domain | Exon 12 | Proline/serine-rich linker region positioned between membrane- and interaction-focused regions; no definitive folded structure or discrete biochemical activity established in the cited review (pqac-00000002) | Likely contributes to conformational flexibility, spacing, and/or structural integrity between domains rather than acting as a standalone catalytic or binding module (pqac-00000002) | No major dedicated binding partner definitively assigned in the cited sources (pqac-00000002) | Consistently retained across isoforms, suggesting selective pressure for structural or organizational importance even though its mechanistic role remains unresolved (pqac-00000002) |
| CLAP domain | Exons 13–16 | Clathrin and adaptor protein 2-binding region; exon 13 also contains an SH3-binding motif for endophilin; exons 14–15 harbor two clathrin-binding sites; variably included by alternative splicing, especially in neuronal isoforms and some cardiac isoforms containing exon 13 (pqac-00000002, pqac-00000007) | Organizes endocytic machinery; promotes clathrin-coated pit/vesicle formation, membrane trafficking, and vesicle biogenesis at plasma membrane and trans-Golgi/endosomal compartments (pqac-00000007, pqac-00000013) | Clathrin, AP2, endophilin; contributes to pathways involving dynamin, synaptojanin, amphiphysin-related endocytic machinery (pqac-00000007, pqac-00000013) | Exon 13 can interact intramolecularly with SH3 to impose an autoinhibited closed conformation; partner binding to CLAP or SH3 can shift BIN1 toward an open active state; extensive alternative splicing tunes tissue specificity (pqac-00000007) |
| Myc-binding domain (MBD) | Exons 17–18 | C-terminal region preceding SH3; exon 18 is constitutive while exon 17 is alternatively spliced and required for full Myc-binding activity; associated with nuclear-localized isoforms (pqac-00000007) | Mediates interaction with c-Myc/N-Myc; suppresses Myc-driven transformation; promotes Myc-dependent apoptosis and contributes to tumor-suppressor functions; implicated in nuclear regulatory roles (pqac-00000007, pqac-00000013) | c-Myc, N-Myc; reported links to PARP1, Ku, XRCC4, and ABL1 in BIN1-associated nuclear/DNA damage regulatory functions (pqac-00000007, pqac-00000013) | Functional output depends on alternative splicing of exon 17; Myc can reciprocally repress BIN1 transcription via MIZ1, creating a feedback circuit; some evidence suggests possible intramolecular MBD-SH3 interaction (pqac-00000007, pqac-00000009) |
| SH3 domain | Exons 19–20 | Conserved C-terminal Src homology 3 domain; β-barrel of 5–6 antiparallel β-strands; surface enriched in aromatic and acidic residues for proline-rich motif recognition; retained in all functional isoforms (pqac-00000002, pqac-00000009) | Principal protein-protein interaction hub; recruits fission/scaffold/signaling proteins to curved membranes; central to endocytosis, T-tubule biology, actin remodeling, directed trafficking, and disease-linked interaction networks (pqac-00000000, pqac-00000009) | DNM2/dynamin-2; synaptojanin; tau via Tau 216PTPP219 region; N-WASP; ABL1; MTM1; many additional partners from interactome studies (pqac-00000000, pqac-00000008, pqac-00000009) | Binds proline-rich motifs; can be sequestered intramolecularly by PI or CLAP domains in autoinhibited states; release occurs upon PI(4,5)P2 engagement or partner binding; pathogenic SH3 truncation/variant states disrupt affinity networks and DNM2 recruitment (pqac-00000000, pqac-00000006, pqac-00000008) |


*Table: This table summarizes the major BIN1 protein domains, the exons that encode them, their structural properties, molecular functions, binding partners, and known regulatory mechanisms. It is useful for linking BIN1 isoform architecture to its membrane-remodeling, endocytic, nuclear, and disease-relevant functions.*