Tetraspanins are a family of
membrane protein
Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...
s found in all
multicellular
A multicellular organism is an organism that consists of more than one cell (biology), cell, unlike unicellular organisms. All species of animals, Embryophyte, land plants and most fungi are multicellular, as are many algae, whereas a few organism ...
eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s also referred to as the transmembrane 4 superfamily (TM4SF) proteins. These proteins have four transmembrane
alpha-helices
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix).
The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
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
Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
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
palmitoylation
In molecular biology, palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typic ...
s 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
Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
or viral infection.
A role for tetraspanins in
platelet
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
s was demonstrated by the bleeding phenotypes of CD151- and TSSC6-deficient mice, which exhibit impaired "outside-in" signalling through
αIIbβ3, the major platelet
integrin
Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
. It is hypothesized that tetraspanins interact with and regulate other platelet receptors.
List of human tetraspanins
See also
*
List of human clusters of differentiation
Relevance to parasite vaccines
The
schistosome
''Schistosoma'' is a genus of trematodes, commonly known as blood flukes. They are parasitic flatworms responsible for a highly significant group of infections in humans termed ''schistosomiasis'', which is considered by the World Health Organ ...
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
Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever is a neglected tropical helminthiasis, disease caused by parasitism, parasitic Schistosoma, flatworms called schistosomes. It affects both humans and animals. It affects ...
).
[Scientific American May 2008, referring to McManus & Loukas Clinical Microbiology reviews V21,N1,p225-242 (Jan 2008)]
References
External links
InterPro on Tetraspanins
{{Membrane proteins
Integral membrane proteins
Protein domains
Immunology