Siglec-14

Siglec-14 (Sialic acid-binding ig-like lectin 14) is a type I transmembrane protein mainly expressed on myeloid cells. It forms an activating/inhibitory "paired receptor" pair with the inhibitory receptor Siglec-5. Through an arginine residue in its transmembrane region, Siglec-14 associates with the adaptor protein DAP12. Upon activation, the ITAM motif of DAP12 recruits Syk kinase and initiates pro-inflammatory signaling. A functional null polymorphism of the SIGLEC14 gene exists in human populations; this loss of function is associated with reduced risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) and decreased susceptibility to tuberculous meningitis. Siglec-14 plays important regulatory roles in pathogen recognition and tumor immunity.