| Binding Partner | Interaction Domain (on CD2AP) | Cellular Context/Location | Functional Role |
|---|---|---|---|
| Nephrin | Primarily C-terminal/adaptor interface; CD2AP functions as a scaffold linking nephrin to downstream cytoskeletal machinery | Podocyte slit diaphragm, lipid raft-associated junctional complex | Couples slit-diaphragm signaling to actin remodeling; helps maintain foot-process architecture and filtration barrier integrity (pqac-00000014, pqac-00000010, pqac-00000003) |
| Podocin | C-terminal region of podocin binds CD2AP scaffold; exact CD2AP subsite not fully resolved in these sources | Podocyte slit diaphragm/lipid rafts | Stabilizes the nephrin–podocin–CD2AP complex and links slit-diaphragm components to the actin cytoskeleton (pqac-00000014, pqac-00000010, pqac-00000003) |
| F-actin / actin cytoskeleton | Direct/functional actin-associating regions outside the SH3 cluster; CD2AP also links actin indirectly through partner proteins | Podocyte foot processes, vesicles, cortical cytoskeleton, phagocytic structures | Structural linkage between membrane complexes and actin; supports cytoskeletal organization, vesicle trafficking, and cell shape control (pqac-00000014, pqac-00000005, pqac-00000004) |
| TrkA | Scaffold interface enabling assembly of receptor-signaling complexes; specific residue-level site not defined here | Neurons, especially NGF-responsive sensory and basal forebrain cholinergic neurons | Coordinates NGF-dependent trophic signaling and receptor-linked retrograde signaling/endocytosis (pqac-00000009) |
| Rab5 | Endosomal/scaffold association; specific CD2AP subdomain not defined here | Rab5-positive endosomes in neurons; endocytic compartments | Supports Rab5-mediated endocytosis and retrograde transport/signaling from internalized receptor complexes (pqac-00000009) |
| PI3K p85 | Scaffold-binding interface assembling signaling complexes downstream of receptors | Neurons; also broader signaling complexes | Promotes PI3K/Akt pathway coupling downstream of trophic receptors such as TrkA (pqac-00000009) |
| Clathrin | Complex formation with CD2AP; likely via non-SH3 scaffold regions coordinating vesicle machinery | Perinuclear region, clathrin-coated/recycling vesicles, podocytes | Connects clathrin to actin and supports vesicle sorting/recycling, including Glut4 trafficking (pqac-00000005) |
| Cortactin | Direct/functional interaction outside core SH3 ligand-binding description in these sources | Podocyte actin cytoskeleton/slit diaphragm-associated actin network | Reinforces the link from nephrin/CD2AP complexes to actin assembly and cytoskeletal remodeling (pqac-00000014) |
| Synaptopodin | Direct/functional interaction; exact subdomain not specified here | Podocyte foot processes and actin-rich structures | Helps connect slit-diaphragm signaling to actin bundle organization and podocyte structural stability (pqac-00000014) |
| ASAP1 | SH3-domain-dependent interaction, involving proline-rich motif recognition | Macrophage and microglial podosomes; MYO1F-associated adaptor module | Adaptor in podosomes/phagocytic structures; implicated in actin-rich adhesion and membrane-remodeling complexes (pqac-00000013, pqac-00000000) |
| SH3BP2 | SH3-domain-dependent interaction, involving proline-rich motif recognition | Immune cells; MYO1F-associated adaptor module | Participates in MYO1F-associated adaptor network in podosomes/phagocytic cups (pqac-00000013, pqac-00000000) |
| SH3KBP1 (CIN85) | SH3-domain-dependent interaction, involving proline-rich motif recognition | Immune cells; podocytes; phagocytic cups | Component of the CASS adaptor module; linked to endocytosis, actin regulation, and phagocytic structures (pqac-00000013, pqac-00000016) |
| GGA2 | Complex formation with CD2AP; specific CD2AP site not resolved here | Podocyte trans-Golgi/GSV trafficking pathway | Sorts Glut4 toward storage vesicles and supports insulin-responsive glucose transporter trafficking (pqac-00000005) |
| TRIM5 | Interaction site not mapped in the retrieved context | Glioblastoma cells | Stabilizes/promotes TRIM5-associated NF-κB signaling, enhancing malignant phenotypes in GBM models (pqac-00000004) |


*Table: This table summarizes major experimentally discussed CD2AP interaction partners, the CD2AP region implicated where available, the cellular context, and the functional consequence of each interaction. It is useful for linking CD2AP's scaffold architecture to specific pathways in podocytes, neurons, immune cells, and cancer.*