Tetraspanin-enriched microdomains. Laminin-binding integrins associate directly with tetraspanin CD151 and are linked to other tetraspanins (such as CD9, CD63, CD81 and CD82) and tetraspanin partner proteins, such as the immunoglobulin superfamily proteins EWI-2 and EWI-F (the EWI proteins). Cytoplasmic effectors associated with tetraspanin-enriched microdomains (TEMs) include type II phosphatidylinositol 4-kinases (PI4KIIs), classical protein kinase C (PKC) isoforms, ezrin–radixin–moesin family proteins (ERMs), and AP adaptor proteins (APs). Key structural features of tetraspanins include large and small extracellular domains (EC2 and EC1, respectively), polar amino acid residues within transmembrane domains 1, 3 and 4, and palmitoylation of intracellular cysteine residues.