SAM (sterile alpha motif) domain of fungal SLA1 proteins is a protein-protein interaction domain. Proteins of this group consist of a few N-terminal SH3 domains followed by SHD1 domain, SAM domain (also known as SHD2) and multiple C-terminal repeats. The yeast SLA1 protein is an endocytic clathrin adaptor. It is associated with a variety of endocytic accessory factors and required for endocytic vesicle formation and for clathrin and actin-dependent cargo recognition. SLA1 binds clathrin through a variant clathrin-binding motif (vCB). The SAM domain negatively regulates this binding by blocking the vCB site. The SAM domains of SLA1 proteins can form oligomers via their mid-loop (ML) and end-helix (EH) regions. Such self-associations apparently are important for SLA1 function. A proposed regulatory model suggests that SAM can be considered a mediator of two aspects of clathrin adaptor function. It plays a role in negative regulation of clathrin binding via an intramolecular interaction with the vCB, and a role in positive regulation of vesicle coat assembly via self-oligomerization.
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