Immunoglobulin superfamily

The immunoglobulin superfamily (IgSF) is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion

Cell adhesion

Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...

 processes of cells

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 (also known as antibodies); they all possess a domain known as an immunoglobulin domain or fold. Members of the IgSF include cell surface antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 receptors, co-receptor

Co-receptor

A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.-Co-receptor Properties:...

s and co-stimulatory

Co-stimulation

During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.- Co-stimulation T cells require :...

 molecules of the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

, molecules involved in antigen presentation

Antigen presentation

Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....

 to lymphocyte

Lymphocyte

A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

s, cell adhesion molecule

Cell adhesion molecule

Cell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....

s, certain cytokine

Cytokine

Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. The sperm-specific protein Izumo, a member of the immunoglobulin superfamily, has also been identified as the only sperm membrane protein essential for sperm-egg fusion.

Immunoglobulin domains

Proteins of the IgSF possess a structural domain known as an immunoglobulin (Ig) domain

Immunoglobulin domain

The immunoglobulin domain is a type of protein domain that consists of a 2-layer sandwich of between 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek key topology....

. Ig domains are named after the immunoglobulin

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 molecules. They contain about 70-110 amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s and are categorised according to their size and function. Ig-domains possess a characteristic Ig-fold, which has a sandwich-like structure formed by two sheets

Beta sheet

The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

 of antiparallel beta strands. Interactions between hydrophobic amino acids on the inner side of the sandwich and highly conserved disulfide bond

Disulfide bond

In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...

s formed between 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 B and F strands, stabilize the Ig-fold. One end of the Ig domain has a section called the complementarity determining region

Complementarity determining region

Complementarity determining regions are regions within antibodies or T cell receptors where these proteins complement an antigen's shape. Thus, CDRs determine the protein's affinity and specificity for specific antigens...

 that is important for the specificity of antibodies for their ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s.

Classification

The Ig like domains can be classified as IgV, IgC1, IgC2, or IgI.

Most Ig domains are either variable (IgV) or constant (IgC).

• IgV: IgV domains with 9 beta strands are generally longer than IgC domains with 7 beta strands.
• IgC1 and IgC2: Ig domains of some members of the IgSF resemble IgV domains in the amino acid sequence, yet are similar in size to IgC domains. These are called IgC2 domains, while standard IgC domains are called IgC1 domains.
• IgI: Other Ig domains exist that are called intermediate (I) domains.

Members of the immunoglobulin superfamily

The Ig domain was reported to be the most populous family of proteins in the human genome with 765 members identified. 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 thought to be due to horizontal gene transfer

Horizontal gene transfer

Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...

.

Members of the immunoglobulin superfamily

Molecule function/category	Examples	Description
Antigen receptors	Antibodies Antibody An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...  or immunoglobulins T cell receptor T cell receptor The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...  chains	Antigen receptors found on the surface of T and B lymphocyte Lymphocyte A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells... s in all jawed vertebrates belong to the IgSF. Immunoglobulin molecules (the antigen Antigen An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...  receptors of B cell B cell B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction... s) are the founding members of the IgSF. In humans, there are five distinct types of immunoglobulin Antibody An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...  molecule all containing a heavy chain with four Ig domains and a light chain with two Ig domains. The antigen receptor of T cell T cell T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are... s is the T cell receptor T cell receptor The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...  (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 the cell membrane Cell membrane The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell... .
Antigen presenting Antigen presentation Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....  molecules	Class I MHC Class II MHC beta-2 microglobulin Beta-2 microglobulin β2 microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells . In humans, the β2 microglobulin protein is encoded by the B2M gene.-Structure and function:...	The ligand Ligand In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from... s for TCRs are major histocompatibility complex Major histocompatibility complex Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...  (MHC) proteins. These come in two forms; MHC class I forms a dimer with a molecule called beta-2 microglobulin Beta-2 microglobulin β2 microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells . In humans, the β2 microglobulin protein is encoded by the B2M gene.-Structure and function:...  (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-receptor Co-receptor A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.-Co-receptor Properties:... s	CD4 CD4 CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984... CD8 CD8 CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene... CD19 CD19 B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...	Co-receptors and accessory molecules: Other molecules on the surfaces of T cells also interact with MHC molecules during TCR engagement. These are known as co-receptor Co-receptor A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.-Co-receptor Properties:... s. In lymphocyte populations, the co-receptor CD4 CD4 CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...  is found on helper T cells and the co-receptor CD8 CD8 CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...  is found on cytotoxic T cell Cytotoxic T cell A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or... s. CD4 has four Ig domains in its extracellular portion and functions as a monomer Monomer A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex... . 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, including CD19 CD19 B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :... , an IgSF molecule with two IgC2-domains.
Antigen receptor accessory molecules	CD3 CD3 receptor In immunology, the CD3 T-Cell Co-Receptor is a protein complex and is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with a molecule known as the T cell receptor and the ζ-chain to generate an activation... -γ, -δ and -ε chains CD79 CD79 CD79 is a transmembrane protein that forms a complex with the B-cell receptor and generates a signal following recognition of antigen by the BCR... a and CD79 CD79 CD79 is a transmembrane protein that forms a complex with the B-cell receptor and generates a signal following recognition of antigen by the BCR... b	A further molecule is found on the surface of T cells that is also involved in signaling from the TCR. CD3 CD3 receptor In immunology, the CD3 T-Cell Co-Receptor is a protein complex and is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with a molecule known as the T cell receptor and the ζ-chain to generate an activation...  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, CD79 CD79 CD79 is a transmembrane protein that forms a complex with the B-cell receptor and generates a signal following recognition of antigen by the BCR... a and CD79 CD79 CD79 is a transmembrane protein that forms a complex with the B-cell receptor and generates a signal following recognition of antigen by the BCR... b that both possess a single Ig domain.
Co-stimulatory or inhibitory molecules	CD28 CD28 CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells... CD80 CD80 Cluster of Differentiation 80 is a protein found on activated B cells and monocytes that provides a costimulatory signal necessary for T cell activation and survival...  and CD86 CD86 Cluster of Differentiation 86 is a protein expressed on antigen-presenting cells that provides costimulatory signals necessary for T cell activation and survival...  (also known as B7.1 and B7.2 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 CD28 CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells... , CTLA-4 CTLA-4 CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system... , program death-1 (PD-1 PD-1 Programmed Death 1, or PD-1, is a Type I membrane protein of 268 amino acids. PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail... ), the B- and T-lymphocyte attenuator (BTLA BTLA B- and T-lymphocyte attenuator is a protein that in humans is encoded by the BTLA gene. BTLA has also been designated as CD272 .- Function :... , CD272), and the inducible T-cell co-stimulator (ICOS, CD278 CD278 Inducible T-cell costimulator is a protein that in humans is encoded by the ICOS gene.CD278 or ICOS is a CD28-superfamily costimulatory molecule that is expressed on activated T cells... ); and their IgSF ligands belong to the B7 family; CD80 CD80 Cluster of Differentiation 80 is a protein found on activated B cells and monocytes that provides a costimulatory signal necessary for T cell activation and survival...  (B7-1), CD86 CD86 Cluster of Differentiation 86 is a protein expressed on antigen-presenting cells that provides costimulatory signals necessary for T cell activation and survival...  (B7-2), ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1).
Receptors on Natural killer cell Natural killer cell Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses... s	Killer-cell immunoglobulin-like receptor Killer-cell immunoglobulin-like receptor Killer-cell immunoglobulin-like receptors , are a family of cell surface proteins found on important cells of the immune system called natural killer cells. They regulate the killing function of these cells by interacting with MHC class I molecules, which are expressed on all cell types... s (KIR)
Receptors on Leukocytes	Leukocyte immunoglobulin-like receptors Leukocyte immunoglobulin-like receptors The leukocyte immunoglobulin-like receptors are a family of receptors possessing extracellular immunoglobulin domains.They are also known as CD85, ILTs and LIR, and can exert immunomodulatory effects on a wide range of immune cells...  (LILR)
IgSF CAM IgSF CAM Immunoglobulin superfamily CAMs are a class of cell adhesion molecules.They are either homophilic or heterophilic and bind integrins or different IgSF CAMs.-Examples:Here is a list of some molecules of this family:... s	NCAMs ICAM-1 ICAM-1 ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system... Type IIa and Type IIb RPTPs, described in Receptor tyrosine kinases/phosphatases subsection below
Cytokine receptor Cytokine receptor Cytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been... s	Interleukin-6 receptor Interleukin-6 receptor Interleukin 6 receptor also known as CD126 is a type I cytokine receptor.... Colony stimulating factor 1 receptor Colony stimulating factor 1 receptor Colony stimulating factor 1 receptor , also known as macrophage colony-stimulating factor receptor , and CD115 , is a cell-surface protein encoded, in humans, by the CSF1R gene...
Growth factor receptor Growth factor receptor A growth factor receptor is a receptor which binds to growth factor.These receptors may use the JAK/STAT, MAP kinase, and PI3 kinase pathways.... s	Platelet-derived growth factor receptor Platelet-derived growth factor receptor Platelet-derived growth factor receptors are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including...  (PDGFR) Mast/stem cell growth factor receptor precursor (SCFR, c-kit, CD117 CD117 Mast/stem cell growth factor receptor also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117 is a protein that in humans is encoded by the KIT gene...  antigen)
Receptor tyrosine kinases/phosphatases	Tyrosine-protein kinase receptor Receptor tyrosine kinase Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....  Tie-1 precursor Type IIa and Type IIb Receptor protein tyrosine phosphatase Protein tyrosine phosphatase Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular... s (RPTPs), including, but not limited to, PTPRM PTPRM Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.- Function :The protein encoded by this gene is a member of the protein tyrosine phosphatase family. Protein tyrosine phosphatases are protein enzymes that remove phosphate moieties from tyrosine... , PTPRK PTPRK Receptor-type tyrosine-protein phosphatase kappa is an enzyme that in humans is encoded by the PTPRK gene.-Interactions:PTPRK has been shown to interact with Beta-catenin and Plakoglobin.-Further reading:... , PTPRU PTPRU Receptor-type tyrosine-protein phosphatase U is an enzyme that in humans is encoded by the PTPRU gene.-Further reading:... , PTPRD PTPRD Receptor-type tyrosine-protein phosphatase delta is an enzyme that in humans is encoded by the PTPRD gene.- Function :The protein encoded by this gene is a member of the protein tyrosine phosphatase family... , PTPRF PTPRF Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene.The protein encoded by this gene is a member of the protein tyrosine phosphatase family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell...
Ig binding receptors	polymeric immunoglobulin receptor Polymeric immunoglobulin receptor Polymeric immunoglobulin receptor is a protein that in humans is encoded by the PIGR gene.It is a Fc receptor which facilitates the secretion of immunoglobulin A and immunoglobulin M.-Further reading:-External links:...  (PIGR) Some Fc receptor Fc receptor An Fc receptor is a protein found on the surface of certain cells - including natural killer cells, macrophages, neutrophils, and mast cells - that contribute to the protective functions of the immune system.... s
Others	CD147 CD90 CD90 Thy-1 or CD90 is a 25–37 kDa heavily N-glycosylated, glycophosphatidylinositol anchored conserved cell surface protein with a single V-like immunoglobulin domain, originally discovered as a thymocyte antigen. Thy-1 can be used as a marker for a variety of stem cells and for the axonal processes... CD7 CD7 CD7 is a human protein encoded by the gene.-External links:... Butyrophilin Butyrophilin Butyrophilin is a family of proteins.Butyrophilin genes constitute a subgroup of at least 10 genes in the Ig superfamily identified in human, mouse, cow, goat and other species.... s (Btn) Titin Titin Titin , also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured...

External links

• Immunoglobulin domain in SUPERFAMILY
  SUPERFAMILY
  SUPERFAMILY is a database of structural and functional annotation for all proteins and genomes.The SUPERFAMILY annotation is based on a collection of hidden Markov models, which represent structural protein domains at the SCOP superfamily level....