Human Siglec‑14 Antibody

Siglecs are sialic acid specific I-type lectins that belong to the immunoglobulin superfamily. Structurally, they are transmembrane proteins with an N-terminal Ig-like V-set domain followed by a varying number of Ig-like C2-set domains (1, 2). Orthologs of Siglec-14 have not been described in mouse or rat. Mature human Siglec-14 consists of a 342 amino acid (aa) extracellular domain (ECD) with one Ig-like V-set domain and two Ig-like C2-set domains, a 23 aa transmembrane segment, and a 15 aa cytoplasmic tail (3). Within the first two Ig-like domains, Siglec-14 shares 99.5% aa sequence identity with Siglec-5, and 51% - 56% with Siglec-3, -6, -7, -8, and -9. Siglec-5 and -14 exhibit similar ligand preference among sialylated glycans, although Siglec-14 binds with higher avidity (3). Siglec-14 does not have the cytoplasmic ITIM sequence that mediates inhibitory signaling of most other Siglecs (2, 3). However, its transmembrane segment contains a charged arginine residue that enables association with the adaptor protein DAP12 (3, 4). Siglec-15 is the only other human Siglec identified to date that associates with DAP12 (5). Siglec-14 mRNA is primarily expressed in bone marrow, spleen, and fetal liver (3). The protein may be expressed on neutrophils, monocytes, and macrophages, as reports describing Siglec-5 on these cells employed some antibodies that also detect Siglec-14 (3, 6, 7). Siglec-5 and -14 likely function as paired receptors with similar ligand specificity and cellular expression but potentially opposing effects on cellular activation (3).