Sialic acid-binding Ig-like lectin 14 (SIGLEC14)

Sialic acid-binding Ig-like lectin 14 (SIGLEC14) is a transmembrane protein encoded by the SIGLEC14 gene and expressed primarily on myeloid cells, including neutrophils, monocytes, and macrophages. It is structurally organized with an extracellular domain that includes one Ig-like V-set domain and two Ig-like C2-set domains, a transmembrane segment containing a critical arginine residue, and a short cytoplasmic tail. Unlike many inhibitory Siglecs, SIGLEC14 lacks an ITIM (immunoreceptor tyrosine-based inhibitory motif) and instead couples with the adaptor protein DAP12, leading to activating ITAM (immunoreceptor tyrosine-based activation motif)–dependent signaling. SIGLEC14 is a paired receptor with close homology to the inhibitory Siglec-5 but delivers opposite cellular signals. Functionally, SIGLEC14 is an activating immune receptor that recognizes sialic acid–containing glycans and contributes to innate immunity. Engagement of SIGLEC14 enhances NLRP3 inflammasome activation and IL-1β secretion when myeloid cells are exposed to bacterial pathogens such as Group B Streptococcus or signals such as ATP and nigericin. The receptor also interacts with non–glycan ligands, notably vimentin. Population genetic diversity at the SIGLEC14 locus affects its expression and functional activity, influencing inflammatory cytokine release and susceptibility to certain infections. Overall, SIGLEC14 is emerging as a significant regulator of human immune responses.

Other names

SIGLEC14Siglec-14UNQ294/PRO333sialic acid-binding Ig-like lectin 14Siglec14siglec-14