Tetraspanin

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Tetraspanin family
Tetraspanin Figure.jpg
Tetraspanins have four transmembrane domains, two extracellular loops and contain a series of highly conserved amino acid residues.
Identifiers
SymbolTetraspanin
Pfam PF00335
Pfam clan CL0347
InterPro IPR000301
PROSITE PDOC00371
SCOP2 1iv5 / SCOPe / SUPFAM
TCDB 8.A.40
OPM superfamily 327
OPM protein 5tcx
CDD cd03127
Hypothetical model of the tetraspanin function Hypothetical model of the tetraspanin function.pdf
Hypothetical model of the tetraspanin function

Tetraspanins are a family of membrane proteins found in all multicellular eukaryotes.

Contents

Tetraspanins, also referred to as the transmembrane 4 superfamily (TM4SF) 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. [1]

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. [2]

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. [3]

List of human tetraspanins

ProteinGeneAliases
TSPAN1 TSPAN1 TSP-1
TSPAN2 TSPAN2 TSP-2
TSPAN3 TSPAN3 TSP-3
TSPAN4 TSPAN4 TSP-4, NAG-2
TSPAN5 TSPAN5 TSP-5
TSPAN6 TSPAN6 TSP-6
TSPAN7 TSPAN7 CD231/TALLA-1/A15
TSPAN8 TSPAN8 CO-029
TSPAN9 TSPAN9 NET-5
TSPAN10 TSPAN10 OCULOSPANIN
TSPAN11 TSPAN11 CD151-like
TSPAN12 TSPAN12 NET-2
TSPAN13 TSPAN13 NET-6
TSPAN14 TSPAN14
TSPAN15 TSPAN15 NET-7
TSPAN16 TSPAN16 TM4-B
TSPAN17 TSPAN17
TSPAN18 TSPAN18
TSPAN19 TSPAN19
TSPAN20 UPK1B UP1b, UPK1B
TSPAN21 TSPAN21 UP1a, UPK1A
TSPAN22 PRPH2 RDS, PRPH2
TSPAN23 TSPAN23 ROM1
TSPAN24 CD151 CD151
TSPAN25 CD53 CD53
TSPAN26 CD37 CD37
TSPAN27 CD82 CD82
TSPAN28 CD81 CD81
TSPAN29 CD9 CD9
TSPAN30 CD63 CD63
TSPAN31 TSPAN31 SAS
TSPAN32 TSPAN32 TSSC6
TSPAN33 TSPAN33

See also

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). [4]

Related Research Articles

Integrin

Integrins are transmembrane receptors that facilitate cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface.

Protein kinase enzyme that adds phosphate groups to other proteins

A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase, the great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets and the other are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.

Transmembrane domain usually denotes a transmembrane segment of single alpha helix of a transmembrane protein. More broadly, a transmembrane domain is any membrane-spanning protein domain.

Cell adhesion molecules (CAMs) are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in creating force and movement and consequently ensure that organs are able to execute their functions. In addition to serving as "molecular glue", cell adhesion is important in affecting cellular mechanisms of growth, contact inhibition, and apoptosis. Oftentimes aberrant expression of CAMs will result in pathologies ranging from frostbite to cancer.

Epithelial sodium channel

The epithelial sodium channel (short: ENaC, also: amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to the ions of sodium (Na+) and that is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. It is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons.

The Cys-loop ligand-gated ion channel superfamily is composed of nicotinic acetylcholine, GABAA, GABAA, glycine, 5-HT3, and zinc-activated (ZAC) receptors. These receptors are composed of five protein subunits which form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). The name of the family refers to a characteristic loop formed by 13 highly conserved amino acids between two cysteine (Cys) residues, which form a disulfide bond near the N-terminal extracellular domain.

Integrin beta 1

Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.

CD9

CD9 is a gene encoding a protein that is a member of the transmembrane 4 superfamily also known as the tetraspanin family. It is a cell surface glycoprotein that consists of four transmembrane regions and has two extracellular loops that contain disulfide bonds which are conserved throughout the tetraspanin family. Also containing distinct palmitoylation sites that allows CD9 to interact with lipids and other proteins.

CD53

Leukocyte surface antigen CD53 is a protein that in humans is encoded by the CD53 gene.

CD63

CD63 antigen is a protein that, in humans, is encoded by the CD63 gene. CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.

CD151

CD151 molecule, also known as CD151, is a human gene.

Platelet membrane glycoproteins are surface glycoproteins found on platelets (thrombocytes) which play a key role in hemostasis. When the blood vessel wall is damaged, platelet membrane glycoproteins interact with the extracellular matrix.

CD81

CD81 molecule, also known as CD81, is a protein which in humans is encoded by the CD81 gene. It is also known as 26 kDa cell surface protein, TAPA-1, and Tetraspanin-28 (Tspan-28).

CD47 Protein-coding gene in humans

CD47 also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD-47 acts as a don't eat me signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis.

TSPAN4

Tetraspanin-4 is a protein that in humans is encoded by the TSPAN4 gene.

Cell surface receptor Class of proteins

Cell surface receptors are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

The GPIb-IX-V complex is a profuse membrane receptor complex originating in megakaryocytes and exclusively functional on the surface of platelets. It primarily functions to mediate the first critical step in platelet adhesion, by facilitating binding to von Willebrand factor (VWF) on damaged sub-endothelium under conditions of high fluid shear stress. Although the primary ligand for the GPIb-V-IX receptor is VWF, it can also bind to a number of other ligands in the circulation such as thrombin, P-selectin, factor XI, factor XII, high molecular weight kininogen as well as bacteria. GPIb-IX-V offers a critical role in thrombosis, metastasis, and the life cycle of platelets, and is implicated in a number of thrombotic pathological processes such as stroke or myocardial infarction.

Collagen, type XXIII, alpha 1

Collagen α-1 (XXIII) chain is a protein encoded by COL23A1 gene, which is located on chromosome 5q35 in humans, and on chromosome 11B1+2 in mice. The location of this gene was discovered by genomic sequence analysis.

Bacterial Leucine Transporter

Bacterial Leucine Transporter (LeuT) is a bundled twelve alpha helix protein which belongs to the family of transporters that shuttle amino acids in and out of bacterial cells. Specialized in small hydrophobic amino acids such as leucine and alanine, this transporter is powered by the gradient of sodium ions that is normally maintained by healthy cells across their membranes. LeuT acts as a symporter, which means that it links the passage of a sodium ion across the cell membrane with the transport of the amino acid in the same direction. It was first crystallized to understand the inner molecular mechanisms of antidepressant's work since it has a close resemblance with the human neurotransmitter transporters that these drugs block, thus inhibiting the reuptake of chemical messengers across the cell membrane of nerve axons and glial cells.

Tight junction proteins are molecules situated at the tight junctions of epithelial, endothelial and myelinated cells. This mutliprotein junctional complex has a regulatory function in passage of ions, water and solutes through the paracellular pathway. It can also coordinate the motion of lipids and proteins between the apical and basolateral surfaces of the plasma membrane. Thereby tight junction conducts signaling molecules, that influence the differentiation, proliferation and polarity of cells. So tight junction plays a key role in maintenance of osmotic balance and trans-cellular transport of tissue specific molecules. Nowadays is known more than 40 different proteins, that are involved in these selective TJ channels.

References

  1. Hemler ME (2005). "Tetraspanin functions and associated microdomains". Nat. Rev. Mol. Cell Biol. 6 (10): 801–11. doi:10.1038/nrm1736. PMID   16314869. S2CID   5906694.
  2. Wright MD, Tomlinson MG (1994). "The ins and outs of the transmembrane 4 superfamily". Immunol. Today. 15 (12): 588–94. doi:10.1016/0167-5699(94)90222-4. PMID   7531445.
  3. Goschnick MW, Lau LM, Wee JL, Liu YS, Hogarth PM, Robb LM, Hickey MJ, Wright MD, Jackson DE (2006). "Impaired "outside-in" integrin alphaIIbbeta3 signaling and thrombus stability in TSSC6-deficient mice". Blood. 108 (6): 1911–8. doi: 10.1182/blood-2006-02-004267 . PMID   16720835.
  4. Scientific American May 2008, referring to McManus & Loukas Clinical Microbiology reviews V21,N1,p225-242 (Jan 2008)