Structure and domain functions of TSPANs. TSPANs are characterized by the presence of 4 transmembrane domains (1-4). There are multiple regions within the protein that mediate key effects. (A) Disulphide-stabilized (green spheres) variable region of the large extracellular loop (EC2) responsible for the unique interactions specific to each TSPAN. (B) The conserved region of the EC2 loop mediates homodimerization. (C) Transmembrane regions are important for the formation of TEMs. (D) Palmitoylation sites are crucial to the proper formation of new TEMs and play a role in signaling. (E) The C-terminus is responsible for interacting with signaling and cytoskeletal proteins.