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The immunoglobulin superfamily (IgSF) is a large
protein superfamily A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...
of
cell surface The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
and soluble
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that are involved in the recognition, binding, or
adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can be ...
processes of cells. Molecules are categorized as members of this
superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...
based on shared structural features with
immunoglobulins An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
(also known as antibodies); they all possess a domain known as an immunoglobulin domain or fold. Members of the IgSF include cell surface
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
receptors,
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. Properties The t ...
s and
co-stimulatory Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activa ...
molecules of the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
, molecules involved in
antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now ...
to
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s,
cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s, certain
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. Otherwise, the sperm-specific protein
IZUMO1 Izumo sperm-egg fusion protein 1 (Sperm-specific protein izumo) is encoded in humans by the ''IZUMO1'' gene. In mammalian fertilisation, IZUMO1 binds to its egg receptor counterpart, Juno, to facilitate recognition and fusion of the gametes. ...
, 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 In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
known as an immunoglobulin (Ig) domain. Ig domains are named after the
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
molecules. They contain about 70-110
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s and are categorized according to their size and function. Ig-domains possess a characteristic Ig-fold, which has a sandwich-like structure formed by two
sheets A bed sheet is a rectangular piece of cloth used either singly or in a pair as bedding, which is larger in length and width than a mattress, and which is placed immediately above a mattress or bed, but below blankets and other bedding (such as ...
of antiparallel
beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
s. Interactions between hydrophobic amino acids on the inner side of the sandwich and highly conserved
disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s formed between
cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...
residues in the B and F strands, stabilize the Ig-fold.


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

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 likely to be due to divergence from a shared ancestor of eukaryotic immunoglobulin superfamily domains.


References


External links

* Transmembrane human proteins from immunoglobulin superfamily classified a
receptorsligands
an
adhesion proteins

Immunoglobulin domain
in
SUPERFAMILY SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...
{{Cytokine receptors Receptors Immunology Protein superfamilies