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 (small extracellular domain or loop (SED/SEL or EC1) and one longer, typically 100 amino acid residues (large extracellular domain/loop (LED/LEL or EC2). Although several protein families have four transmembrane domains, tetraspanins are defined by conserved domains listed under pfam00335.12 . The key features are four or more cysteine residues in the EC2 domain, with two in a highly conserved 'CCG' motif.
Research into this field is relatively recent (less than 20 years) and therefore there is much to learn about the function of specific tetraspanins. Generally, tetraspanins are often thought to act as scaffolding proteins, anchoring multiple proteins to one area of the cell membrane.
Tetraspanins are highly conserved between species. Some tetraspanins can have N-linked glycosylations on the long extracellular loop (LEL, EC2) and palmitoylations at a CXXC motif in their transmembrane region.
There are 34 tetraspanins in mammals, 33 of which have also been identified in humans. Tetraspanins display numerous properties that indicate their physiological importance in cell adhesion, motility, activation and proliferation, as well as their contribution to pathological conditions such as metastasis or viral infection.
A role for tetraspanins in platelets was demonstrated by the bleeding phenotypes of CD151- and TSSC6-deficient mice, which exhibit impaired "outside-in" signalling through alphaIIbbeta3, the major platelet integrin. it is hypothesized that tetraspanins interact with and regulate other platelet receptors. 
List of human tetraspanins
|TSPAN11||CD151-like, may not be expressed in humans|
- Hemler, M.E. 2005. Tetraspanin functions and associated microdomains. Nature Molecular Cell Biology Reviews 6: 801-811.
- Wright, M.D. and Tomlinson, M.G. (1994) The ins and outs of the transmembrane 4 superfamily. Immunol Today 15, 588-594
- Goschnick et al. (2006) Impaired "outside-in" integrin alphaIIbbeta3 signaling and thrombus stability in TSSC6-deficient mice. Blood. 2006;108(6):1911-8.