Tetraspanins are a family of membrane proteins found in all multicellular eukaryotes also referred to as the transmembrane 4 superfamily (TM4SF) proteins. These proteins have four transmembrane alpha-helices 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 alpha-helices, tetraspanins are defined by conserved amino acid sequences including four or more cysteine residues in the EC2 domain, with two in a highly conserved 'CCG' motif. 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 αIIbβ3, the major platelet integrin. It is hypothesized that tetraspanins interact with and regulate other platelet receptors.
List of human tetraspanins Protein Gene Aliases TSPAN1 TSP-1 TSPAN2 TSP-2 TSPAN3 TSP-3 TSPAN4 TSP-4, NAG-2 TSPAN5 TSP-5 TSPAN6 TSP-6 TSPAN7 CD231/TALLA-1/A15 TSPAN8 CO-029 TSPAN9 NET-5 TSPAN10 OCULOSPANIN TSPAN11 CD151-like TSPAN12 NET-2 TSPAN13 NET-6 TSPAN14 TSPAN15 NET-7 TSPAN16 TM4-B TSPAN17 TSPAN18 TSPAN19 TSPAN20 UP1b, UPK1B TSPAN21 UP1a, UPK1A TSPAN22 RDS, PRPH2 TSPAN23 ROM1 TSPAN24 CD151 TSPAN25 CD53 TSPAN26 CD37 TSPAN27 CD82 TSPAN28 CD81 TSPAN29 CD9 TSPAN30 CD63 TSPAN31 SAS TSPAN32 TSSC6 TSPAN33
See also List of human clusters of differentiation
Relevance to parasite vaccines The schistosome worms make two tetraspanins: TSP-1 and TSP-2. TSP-2 antibodies are found in some people who seem to have immunity to schistosome infection (Schistosomiasis).Scientific American May 2008, referring to McManus & Loukas Clinical Microbiology reviews V21,N1,p225-242 (Jan 2008)
References
External links InterPro on Tetraspanins