Second Src Homology 3 domain (SH3B) of CD2-associated protein
CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.
Feature 1:peptide ligand binding site [polypeptide binding site]
Evidence:
Structure:2U23: human Cms bind a proline-rich peptide from human Rin3, contacts at 4A.
Comment:based on the binding of the first SH3 (SH3A) domains of human CMS and CIN85 to Cbl-b peptide, and on the binding of the second SH3 (SH3B) domain of human CMS to Rin3 peptide
Jiyao W et al.(2023). "The conserved domain database in 2023.",