Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Angata, Takashi; Hayakawa, Toshiyuki; Yamanaka, Masahiro; Ajit Varki; Nakamura, Mitsuru
Year of Publication: 2006
Journal: FASEB J
Volume: 20
Issue: 12
Pagination: 1964-73
Date Published: 2006 Oct
Publication Language: eng
ISSN: 1530-6860
Keywords: Adaptor Proteins, Signal Transducing, Animals, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Arginine, Evolution, Molecular, Gene Conversion, Humans, Lectins, Membrane Proteins, Polysaccharides, Primates, Protein Binding, Protein Structure, Tertiary, Receptors, Cell Surface, Receptors, Immunologic

Immune receptors that show high mutual sequence similarity and have antagonizing signaling properties are called paired receptors, and are believed to fine-tune immune responses. Siglecs are sialic acid-recognizing receptors of the immunoglobulin (Ig) superfamily expressed on immune cells. Human Siglec-5, encoded by SIGLEC5 gene, has four extracellular Ig-like domains and a cytosolic inhibitory motif. We discovered human Siglec-14 with three Ig-like domains, encoded by the SIGLEC14 gene, adjacent to SIGLEC5. Human Siglec-14 has almost complete sequence identity with human Siglec-5 at the first two Ig-like domains, shows a glycan binding preference similar to that of human Siglec-5, and associates with the activating adapter protein DAP12. Thus, Siglec-14 and Siglec-5 appear to be the first glycan binding paired receptors. Near-complete sequence identity of the amino-terminal part of human Siglec-14 and Siglec-5 indicates partial gene conversion between SIGLEC14 and SIGLEC5. Remarkably, SIGLEC14 and SIGLEC5 in other primates also show evidence of gene conversions within each lineage. Evidently, balancing the interactions between Siglec-14, Siglec-5 and their common ligand(s) had selective advantage during the course of evolution. The "essential arginine" critical for sialic acid recognition in both Siglec-14 and Siglec-5 is present in humans but mutated in almost all great ape alleles.

DOI: 10.1096/fj.06-5800com
Alternate Journal: FASEB J.