Tetraspanin
Encyclopedia
Tetraspanins are a family of membrane protein
s found in all multicellular eukaryote
s.
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.
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 palmitoylation
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
or viral infection.
A role for tetraspanins in platelet
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. it is hypothesized that tetraspanins interact with and regulate other platelet receptors.
).
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
s found in all multicellular eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s.
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
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
listed in the Protein Families database
Pfam
Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models.- Features :For each family in Pfam one can:* Look at multiple alignments* View protein domain architectures...
under pfam00335.12. The key features are four or more cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
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 palmitoylation
Palmitoylation
S-Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine residues of membrane proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their...
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
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
, as well as their contribution to pathological conditions such as metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
or viral infection.
A role for tetraspanins in platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s was demonstrated by the bleeding phenotypes of CD151- and TSSC6-deficient mice, which exhibit impaired "outside-in" signalling through αIIbβ3
Glycoprotein IIb/IIIa
In medicine, glycoprotein IIb/IIIa is an integrin complex found on platelets. It is a receptor for fibrinogen and aids in platelet activation. The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence...
, 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 TSPAN2 Tetraspanin-2 is a protein that in humans is encoded by the TSPAN2 gene.-Further reading:... |
TSP-2 | |
| TSPAN3 TSPAN3 Tetraspanin-3 is a protein that in humans is encoded by the TSPAN3 gene.-Further reading:... |
TSP-3 | |
| TSPAN4 TSPAN4 Tetraspanin-4 is a protein that in humans is encoded by the TSPAN4 gene.-Interactions:TSPAN4 has been shown to interact with CD9, ITGA6, CD29, CD49c and CD81.-Further reading:... |
TSP-4, NAG-2 | |
| TSPAN5 | TSP-5 | |
| TSPAN6 TSPAN6 Tetraspanin-6 is a protein that in humans is encoded by the TSPAN6 gene.-Further reading:... |
TSP-6 | |
| TSPAN7 TSPAN7 Tetraspanin-7 is a protein that in humans is encoded by the TSPAN7 gene.-Further reading:... |
CD231/TALLA-1/A15 | |
| TSPAN8 TSPAN8 Tetraspanin-8 is a protein that in humans is encoded by the TSPAN8 gene.-Further reading:... |
CO-029 | |
| TSPAN9 | NET-5 | |
| TSPAN10 | OCULOSPANIN | |
| TSPAN11 | CD151-like | |
| TSPAN12 TSPAN12 TSPAN12, also known as NET-2 or TM4SF12 is a tetraspanin protein that is found in the membrane of a variety of cells. It has an unusually long C-terminal intracellular tail of approximately 60 amino acids.-Function:... |
NET-2 | |
| TSPAN13 TSPAN13 Tetraspanin-13 is a protein that in humans is encoded by the TSPAN13 gene.-Further reading:... |
NET-6 | |
| TSPAN14 | ||
| TSPAN15 | NET-7 | |
| TSPAN16 | TM4-B | |
| TSPAN17 | ||
| TSPAN18 | ||
| TSPAN19 | ||
| TSPAN20 UPK1B Uroplakin 1B, also known as UPK1B, is a protein which in humans is encoded by the UPK1B gene.- Function :The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by... |
UP1b, UPK1B UPK1B Uroplakin 1B, also known as UPK1B, is a protein which in humans is encoded by the UPK1B gene.- Function :The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by... |
|
| TSPAN21 | UP1a, UPK1A | |
| TSPAN22 | RDS, PRPH2 Peripherin 2 Peripherin-2 is a protein, that in humans is encoded by the PRPH2 gene. Peripherin-2 is found in the rod and cone cells of the retina of the eye... |
|
| TSPAN23 | ROM1 | |
| TSPAN24 CD151 CD151 molecule , also known as CD151 , is a human gene.-Further reading:... |
CD151 CD151 CD151 molecule , also known as CD151 , is a human gene.-Further reading:... |
|
| TSPAN25 CD53 Leukocyte surface antigen CD53 is a protein that in humans is encoded by the CD53 gene.-External links:... |
CD53 CD53 Leukocyte surface antigen CD53 is a protein that in humans is encoded by the CD53 gene.-External links:... |
|
| TSPAN26 CD37 Leukocyte antigen CD37 is a protein that in humans is encoded by the CD37 gene.-External links:... |
CD37 CD37 Leukocyte antigen CD37 is a protein that in humans is encoded by the CD37 gene.-External links:... |
|
| TSPAN27 | CD82 CD82 (gene) CD82 is a human protein encoded by the gene.-Interactions:CD82 has been shown to interact with CD19, CD63 and CD234-External links:... |
|
| TSPAN28 | CD81 | |
| TSPAN29 CD9 CD9 antigen is a protein that in humans is encoded by the CD9 gene.-Interactions:CD9 has been shown to interact with TSPAN4, PTGFRN, CD81, CD117, CD46, CD29 and CD49c.-Further reading:... |
CD9 CD9 CD9 antigen is a protein that in humans is encoded by the CD9 gene.-Interactions:CD9 has been shown to interact with TSPAN4, PTGFRN, CD81, CD117, CD46, CD29 and CD49c.-Further reading:... |
|
| TSPAN30 CD63 CD63 antigen is a protein that in humans is encoded by the CD63 gene.CD63 is a good marker for flow cytometric quantification of in vitro activated basophils for diagnosis of IgE-mediated allergy. The test is commonly designated as basophil activation test -Interactions:CD63 has been shown to... |
CD63 CD63 CD63 antigen is a protein that in humans is encoded by the CD63 gene.CD63 is a good marker for flow cytometric quantification of in vitro activated basophils for diagnosis of IgE-mediated allergy. The test is commonly designated as basophil activation test -Interactions:CD63 has been shown to... |
|
| TSPAN31 TSPAN31 Tetraspanin-31 is a protein that in humans is encoded by the TSPAN31 gene.-Further reading:... |
SAS | |
| TSPAN32 TSPAN32 Tetraspanin-32 is a protein that in humans is encoded by the TSPAN32 gene.-Further reading:... |
TSSC6 | |
| TSPAN33 | ||
| TSPAN34 |
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 (SchistosomiasisSchistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
).