Siglec-17

Siglec-17 is a Siglec gene that encodes a receptor in non-human primates but exists only as a pseudogene in humans, representing one of the human-specific Siglec losses during evolution. In species such as macaques, Siglec-17 is an activating receptor whose type I transmembrane protein contains a V-set sialic acid-binding domain and a positively charged transmembrane residue that pairs with DAP12, transmitting activating signals through SYK/TYROBP in myeloid cells; its ligand-binding specificity includes α2,3-linked sialylated glycans. The human SIGLEC17P pseudogene resulted from an Alu-mediated recombination event introducing premature stop codons. The absence of functional Siglec-17 in humans, combined with similar losses (Siglec-13) and gains (Siglec-11) in the human lineage, is hypothesized to reflect evolutionary responses to pathogen-mediated selection on sialic acid-recognition systems, potentially contributing to species differences in inflammatory responses, susceptibility to sialylated pathogens, and chronic inflammatory diseases. Siglec-17 thus serves as a molecular fossil illuminating the evolutionary plasticity of the Siglec family.