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Tetraspanin, extracellular domain or large extracellular loop (LEL). Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model spans the extracellular domain between the 3rd and 4th trans-membrane segment. The tetraspanin family contains CD9, CD63, CD37, CD53, CD82, CD151, and CD81, amongst others. Tetraspanins are involved in diverse processes such as cell activation and proliferation, adhesion and motility, differentiation, cancer, and others. Their various functions may relate to their ability to act as molecular facilitators, grouping specific cell-surface proteins and affecting formation and stability of signaling complexes. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web", which may also include integrins.
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Jiyao W et al.(2023). "The conserved domain database in 2023.",