This entry represents the extracellular domain or large extracellular loop (LEL) of CD9. This extracellular domain lies between the 3rd and 4th trans-membrane segment. CD9 belongs to the tetraspanin family of membrane proteins and is found in virtually all tissues, it is potentially involved in developmental processes. It associates with the tetraspanins CD81 and CD63, as well as with some integrin, and has been shown to be involved in a variety of activation, adhesion, and cell motility functions, as well as cell-cell interactions - such as during fertilization [, , ]. Tetraspanins are a distinct family of cell surface proteins, containing four conserved transmembrane domains: a small outer loop (EC1), a larger outer loop (EC2), a small inner loop (IL) and short cytoplasmic tails. They contain characteristic structural features, including 4-6 conserved extracellular cysteine residues, and polar residues within transmembrane domains. A fundamental role of tetraspanins appears to be organising other proteins into a network of multimolecular membrane microdomains, sometimes called the 'tetraspanin web'. Within this web there are primary complexes in which tetraspanins show robust, specific, and direct lateral associations with other proteins. The strong tendency of tetraspanins to associate with each other probably contributes to the assembly of a network of secondary interactions in which non-tetraspanin proteins are associated with each other via palmitoylated tetraspanins acting as linker proteins. In addition, the association of lipids, such as gangliosides and cholesterol, probably contributes to the assembly of even larger tetraspanin complexes, which have some lipid raft-like properties (e.g. resistance to solubilization in non-ionic detergents). Within the tetraspanin web, tetraspanin proteins can associate not only with integrins and other transmembrane proteins, but also with signalling enzymes such as protein kinase C and phosphatidylinositol-4 kinase. Thus, the tetraspanin web provides a mechanistic framework by which membrane protein signalling can be expanded into a lateral dimension [].
