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The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins, also known as antibodies. They all possess a domain known as an immunoglobulin domain or fold, which is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino acids. Members of the IgSF include cell surface antigen receptors, co-receptors and co-stimulatory molecules of the immune system, molecules involved in antigen presentation to lymphocytes, cell adhesion molecules, certain cytokine receptors and intracellular muscle proteins.
IgSF members are commonly related to immunological recognition, a number of related molecules participate in developmental and homeostatic phenomena. Manipulation of the IgSF by recombinant methodologies including bacteriophage and yeast display offers in vitro approaches to increase the available diversity of novel structures for almost limitless functions.
According to their molecule functions, members of the immunoglobulin superfamily could be classified into several categories. Antigen receptors, antigen presenting molecules, co-receptors, antigen receptor accessory molecules, co-stimulatory or inhibitory molecules, receptors on natural killer cells, receptors on Leukocytes, IgSF CAMs, cytokine receptors, growth factor receptors, receptor tyrosine kinases/phosphatases, Ig binding receptors
and others. They are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin, and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein–protein and protein–ligand interactions.
|Antigen receptors found on the surface of T and B lymphocytes in all jawed vertebrates belong to the IgSF.|
|Antibodies or immunoglobulins||T cell receptor chains|
|Antigen presenting molecules include Class I MHC, Class II MHC and beta-2 microglobulin. The ligands for TCRs(T cell receptors) are major histocompatibility complex (MHC) proteins.|
|Other molecules on the surfaces of T cells also interact with MHC molecules during TCR engagement, which are known as co-receptors. In lymphocyte populations, the co-receptor CD4 is found on helper T cells and the co-receptor CD8 is found on cytotoxic T cells. Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4.|
|Antigen receptor accessory molecules is also involved in signaling from the TCR.|
|Co-stimulatory and inhibitory signaling receptors and ligands control the activation, expansion and effector functions of cells.|
|IgSF CAMs are groups of homologous cell adhesion molecules (CAMs), and CD2 subset of IgSF occupies the vast majority. Programmed death-1 (PDCD1), as mmune checkpoint, down regulates the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance. PD-1 inhibitors can activate the immune system to attack tumors.|
|Cytokine receptors are receptors that bind cytokines. Cytokines act on their target cells by binding specific membrane receptors. Many cell functions are regulated by members of the cytokine receptors. |
|Interleukin-1 receptor||Colony stimulating factor 1 receptor|
|Growth factor receptors are the first stop in cells where the signaling cascade for cell differentiation and proliferation begins. Growth factors, which are ligands that bind to the receptor are the initial step to activating the growth factor receptors and tells the cell to grow and/or divide.|
Platelet-derived growth factor receptor (PDGFR)
|Mast/stem cell growth factor receptor precursor (SCFR, c-kit, CD117 antigen)|
|Receptor tyrosine kinases/phosphatases refer to a group of protein tyrosine phosphatases (RPTPs).|
|Ig binding receptors are series of Fc receptors. Polymeric immunoglobulin receptor (pIgR) is a typical protein that in humans is encoded by the PIGR gene. It is a Fc receptor which facilitates the secretion of the soluble polymeric isoforms of immunoglobulin A and immunoglobulin M.|
|Other members of the immunoglobulin superfamily.|