| Immunoglobulin superfamily | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Antibody in complex with hen egg white lysozyme.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | IgSF | ||||||||
| Pfam | PF00047 | ||||||||
| Pfam clan | CL0159 | ||||||||
| ECOD | 11.1.1 | ||||||||
| InterPro | IPR013151 | ||||||||
| PROSITE | PS50835 | ||||||||
| SCOP2 | 1tlk /SCOPe /SUPFAM | ||||||||
| OPM superfamily | 193 | ||||||||
| OPM protein | 3bib | ||||||||
| CDD | cd00096 | ||||||||
| Membranome | 2 | ||||||||
| |||||||||
| Immunoglobulin-like (ligands) | |
|---|---|
| Identifiers | |
| Symbol | Ig protein ligands |
| Membranome | 64 |
| Immunoglobulin-like adhesion molecules | |
|---|---|
| Identifiers | |
| Symbol | IgSF CAM |
| Membranome | 110 |
Theimmunoglobulin superfamily (IgSF) is a largeprotein superfamily ofcell surface and solubleproteins that are involved in the recognition, binding, oradhesion processes ofcells. Molecules are categorized as members of thissuperfamily based on shared structural features withimmunoglobulins (also known as antibodies); they all possess a domain known as animmunoglobulin domain or fold. Members of the IgSF include cell surfaceantigen receptors,co-receptors andco-stimulatory molecules of theimmune system, molecules involved inantigen presentation tolymphocytes,cell adhesion molecules, certaincytokine receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. Otherwise, the sperm-specific proteinIZUMO1, a member of the immunoglobulin superfamily, has also been identified as the only sperm membrane protein essential for sperm-egg fusion.
Proteins of the IgSF possess astructural domain known as animmunoglobulin (Ig) domain. Ig domains are named after theimmunoglobulin molecules. They contain about 70-110amino acids and are categorized according to their size and function.[2] Ig-domains possess a characteristicIg-fold, which has a sandwich-like structure formed by twosheets of antiparallelbeta strands. Interactions between hydrophobic amino acids on the inner side of the sandwich and highly conserveddisulfide bonds formed betweencysteine residues in the B and F strands, stabilize the Ig-fold.[citation needed]
The Ig like domains can be classified as IgV, IgC1, IgC2, or IgI.[3]
Most Ig domains are either variable (IgV) or constant (IgC).
The Ig domain was reported to be the most populous family of proteins in the human genome with 765 members identified.[5] Members of the family can be found even in the bodies of animals with a simple physiological structure such as poriferan sponges. They have also been found in bacteria, where their presence is likely to be due to divergence from a shared ancestor of eukaryotic immunoglobulin superfamily domains.[6]
| Molecule function/category | Examples | Description |
|---|---|---|
| Antigen receptors |
| Antigen receptors found on the surface of T and Blymphocytes in all jawed vertebrates belong to the IgSF. Immunoglobulin molecules (theantigen receptors ofB cells) are the founding members of the IgSF. In humans, there are five distinct types ofimmunoglobulin molecule all containing a heavy chain with four Ig domains and a light chain with two Ig domains. The antigen receptor ofT cells is theT-cell receptor (TCR), which is composed of two chains, either the TCR-alpha and -beta chains, or the TCR-delta and gamma chains. All TCR chains contain two Ig domains in the extracellular portion; one IgV domain at the N-terminus and one IgC1 domain adjacent to thecell membrane. |
| Antigen presenting molecules | Theligands for TCRs aremajor histocompatibility complex (MHC) proteins. These come in two forms; MHC class I forms a dimer with a molecule calledbeta-2 microglobulin (β2M) and interacts with the TCR on cytotoxic T cells and MHC class II has two chains (alpha and beta) that interact with the TCR on helper T cells. MHC class I, MHC class II and β2M molecules all possess Ig domains and are therefore also members of the IgSF. | |
| Co-receptors | Co-receptors and accessory molecules: Other molecules on the surfaces of T cells also interact with MHC molecules during TCR engagement. These are known asco-receptors. In lymphocyte populations, the co-receptorCD4 is found onhelper T cells and the co-receptorCD8 is found oncytotoxic T cells. CD4 has four Ig domains in its extracellular portion and functions as amonomer. CD8, in contrast, functions as a dimer with either two identical alpha chains or, more typically, with an alpha and beta chain. CD8-alpha and CD8-beta each has one extracellular IgV domain in its extracellular portion. A co-receptor complex is also used by the BCR, includingCD19, an IgSF molecule with two IgC2-domains. | |
| Antigen receptor accessory molecules | A further molecule is found on the surface of T cells that is also involved in signaling from the TCR.CD3 is a molecule that helps to transmit a signal from the TCR following its interaction with MHC molecules. Three different chains make up CD3 in humans, the gamma chain, delta chain and epsilon chain, all of which are IgSF molecules with a single Ig domain. Similar to the situation with T cells, B cells also have cell surface co-receptors and accessory molecules that assist with cell activation by the B Cell Receptor (BCR)/immunoglobulin. Two chains are used or signaling,CD79a andCD79b that both possess a single Ig domain. | |
| Co-stimulatory or inhibitory molecules | Co-stimulatory or inhibitory molecules: Co-stimulatory and inhibitory signaling receptors and ligands control the activation, expansion and effector functions of cells. One major group of IgSF co-stimulatory receptors are molecules of the CD28 family;CD28,CTLA-4, program death-1 (PD-1), the B- and T-lymphocyte attenuator (BTLA, CD272), and the inducible T-cell co-stimulator (ICOS,CD278);[7] and their IgSF ligands belong to the B7 family;CD80 (B7-1),CD86 (B7-2),ICOS ligand,PD-L1 (B7-H1),PD-L2 (B7-DC),B7-H3, andB7-H4 (B7x/B7-S1).[8] | |
| Receptors onNatural killer cells | ||
| Receptors onLeukocytes | ||
| IgSF CAMs | ||
| Cytokine receptors | ||
| Growth factor receptors |
| |
| Receptor tyrosine kinases/phosphatases |
| |
| Ig binding receptors | ||
| Cytoskeleton | ||
| Others |