Immunoreceptor tyrosine-based activation motif
Encyclopedia
An immunoreceptor tyrosine-based activation motif (ITAM) (in the antagonistic case ITIM
, I for inhibition) is a conserved sequence of four amino acid
s that is repeated twice in the cytoplasmic tails of certain cell surface proteins of the immune system
.
separated from a leucine
or isoleucine
by any two other amino acid
s, giving the signature YxxL. Two of these signatures are typically separated by between 7 and 12 amino acids in the tail of the molecule (YxxLx(7-12)YxxL).
and ζ-chains of the T cell receptor
complex, the CD79
-alpha and -beta chains of the B cell receptor complex, and certain Fc receptor
s. The tyrosine residues within these motifs become phosphorylated following interaction of the receptor molecules with their ligand
s and form docking sites for other proteins involved in the signaling
pathways of the cell.
Immunoreceptor tyrosine-based inhibitory motif
An immunoreceptor tyrosine-based inhibition motif , is a conserved sequence of amino acids that is found in the cytoplasmic tails of many inhibitory receptors of the immune system...
, I for inhibition) is a conserved sequence of four 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 that is repeated twice in the cytoplasmic tails of certain cell surface proteins 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...
.
Structure
The motif contains a tyrosineTyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
separated from a leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
or isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
by any two other 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, giving the signature YxxL. Two of these signatures are typically separated by between 7 and 12 amino acids in the tail of the molecule (YxxLx(7-12)YxxL).
Function
ITAMs are important for signal transduction in immune cells. Hence, they are found in the tails of important cell signaling molecules such as the CD3CD3 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...
and ζ-chains of 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...
complex, the 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...
-alpha and -beta chains of the B cell receptor complex, and certain 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. The tyrosine residues within these motifs become phosphorylated following interaction of the receptor molecules with 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 and form docking sites for other proteins involved in the signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
pathways of the cell.