Immunoreceptor tyrosine-based inhibitory motif

An immunoreceptor tyrosine-based inhibitory motif (ITIM), is a conserved sequence of amino acids that is found intracellularly in the cytoplasmic domains of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family found on immune cells.^[1][2] These immune cells include T cells, B cells, NK cells, dendritic cells, macrophages and mast cells.  ITIMs have similar structures of S/I/V/LxYxxI/V/L, where x is any amino acid, Y is a tyrosine residue that can be phosphorylated, S is the amino acid serine, I is the amino acid isoleucine, and V is the amino acid valine.^[3] ITIMs recruit SH2 domain-containing phosphatases, which inhibit cellular activation. ITIM-containing receptors often serve to target immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors, resulting in an innate inhibition mechanism within cells.^[3] ITIM bearing receptors have important role in regulation of immune system allowing negative regulation at different levels of the immune response.^[4]

A list of human candidate ITIM-containing proteins has been generated by proteome-wide scans.^[5] It has included more than 135 proteins with ITIM motif. This list is reportedly expanded by studying rare human SNPs that create the consensus signature S/I/V/LxYxxI/V/L motif.^[6]