Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p
Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. 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:ubiquitin binding site [polypeptide binding site]
Evidence:
Structure:2JT4; Saccharomyces cerevisiae Sla1p third SH3 domain binds ubiquitin; contacts at 4A.
Comment:This site overlaps with the proline-rich ligand binding site. However, ubiquitin binding does not interfere with ligand binding, suggesting a dynamic interplay between the two processes.
Jiyao W et al.(2023). "The conserved domain database in 2023.",