Tetraspanins are a family of membrane proteins found in all multicellular eukaryotes. Tetraspanins, also called tetraspans or the transmembrane 4 superfamily (TM4SF), have four transmembrane domains, intracellular N- and C-termini and two extracellular domains, one short (called the small extracellular domain or loop, SED/SEL or EC1) and one longer, typically 100 amino acid residues (the large extracellular domain/loop, LED/LEL or EC2). Although several protein families have four transmembrane domains, tetraspanins are defined by conserved domains listed in the Protein Families database under pfam00335. 12. The key features are four or more cysteine residues in the EC2 domain, with two in a highly conserved "CCG" motif.