Immunoreceptor tyrosine-based activation motif
An immunoreceptor tyrosine-based activation motif (ITAM) is a conserved sequence of four
Structure
The motif contains a tyrosine separated from a leucine or isoleucine by any two other amino acids, giving the signature YxxL/I.[1] Two of these signatures are typically separated by between 6 and 8 amino acids in the cytoplasmic tail of the molecule (YxxL/Ix(6-8)YxxL/I). However, it is worth noting that in various sources, this consensus sequence differs, mainly in the number of amino acids between individual signatures. Apart from ITAMs which have the structure described above, there is also a variety of proteins containing ITAM-like motifs, which have a very similar structure and function (for example in Dectin-1 protein).[4][5][6]
Function
ITAMs are important for signal transduction, mainly in immune cells. They are found in the cytoplasmic tails of non-catalytic tyrosine-
Other non-catalytic tyrosine-phosphorylated receptors carry a conserved inhibitory motif (ITIM) that, when phosphorylated, results in the inhibition of the signaling pathway via recruitment of phosphatases, namely SHP-1, SHP-2 and SHIP1. This serves not only for inhibition and regulation of signalling pathways related to ITAM-based signalling, but also for termination of signalling.[11][12][13]
Genetic variations
Rare human genetic mutations are catalogued in the human genetic variation databases[14][15][16] which can reportedly result in creation or deletion of ITIM and ITAMs.[17]
Examples
Examples shown below list both proteins that contain the ITAM themselves and proteins that use ITAM-based signalling with the help of associated proteins which contain the motif.
CD3γ, CD3δ, CD3ε, TYROBP (DAP12), FcαRI, FcγRI, FcγRII, FcγRIII, Dectin-1, CLEC-1, CD28, CD72