PROSITE documentation PDOC51055

ITAM motif profiles

Signal transduction by T and B cell antigen receptors and certain receptors for Ig Fc regions involves a conserved sequence motif, termed an immunoreceptor tyrosine-based activation motif (ITAM). It is also found in the cytoplasmic domain of apoptosis receptor. Phosphorylation of the two ITAM tyrosines is a critical event in signal transduction. All (p)2ITAMs, but not their nonphosphorylated counterparts, induced extensive protein tyrosine phosphorylation in permeabilized cells. After binding of the ligand, via SH2 domain (see <PDOC50001>), phosphorylation of the two conserved tyrosines of ITAM creates binding sites for downstream signaling molecules and thus enables the initiation of signalling events. This phosphorylation was found to reflect activation of the src family kinase Lyn and Syk. Different ITAMs may preferentially activate distinct signaling pathways as a consequence of distinct SH2 effector binding preference [1,2]. Furthermore, in viruses, ITAMs may play key roles in viral pathogenesis by regulating viral clearance, immune cell activation, immune cell recruitment through binding of cellular kinases and thereby down regulate their function [3].

This motif can be found in one to three copies and in association with the Ig-like domain (see <PDOC50835>).

Proteins currently known to contain an ITAM motif are:

• Mammalian α and β immunoglobulin proteins, TCR γ receptors, FCR γ receptors subunits, CD3 chains receptors and NFAT activation molecule.
• Hantavirus cytoplasmic elements [3].

Two profiles were developed for this motif. The first one picks up mammalian ITAM while the second one is specific to hantavirus ITAM motif.