Siglec-16

Siglec-16 is an activating Siglec of the CD33-related family, structurally the counterpart of inhibitory Siglec-11 with which it shares near-identical sialic acid-binding V-set domains through gene conversion, creating a paired activating/inhibitory receptor system akin to Siglec-5/Siglec-14. Siglec-16 is a type I transmembrane protein that associates with DAP12 via a charged transmembrane residue, transmitting activating signals through SYK in myeloid cells including brain-resident microglia and tissue macrophages. Its ligand specificity includes α2,8-linked disialylated glycans. In the human population, SIGLEC16 is frequently present as a pseudogene (SIGLEC16P) due to a frameshift polymorphism that introduces a premature stop codon; the functional/pseudogene status varies among individuals. Because Siglec-16 is expressed in microglia, it has been proposed to modulate neuroinflammatory responses, and its activating signaling may counterbalance Siglec-11-mediated inhibition, with the pseudogene status potentially influencing susceptibility to neurodegenerative and infectious diseases. Siglec-16 exemplifies the dynamic birth-and-death evolution of Siglec genes.