%0 Journal Article %J FASEB J %D 2006 %T Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. %A Angata, Takashi %A Hayakawa, Toshiyuki %A Yamanaka, Masahiro %A Ajit Varki %A Nakamura, Mitsuru %K Adaptor Proteins, Signal Transducing %K Animals %K Antigens, CD %K Antigens, Differentiation, Myelomonocytic %K Arginine %K Evolution, Molecular %K Gene Conversion %K Humans %K Lectins %K Membrane Proteins %K Polysaccharides %K Primates %K Protein Binding %K Protein Structure, Tertiary %K Receptors, Cell Surface %K Receptors, Immunologic %X

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.

%B FASEB J %V 20 %P 1964-73 %8 2006 Oct %G eng %N 12 %1

http://www.ncbi.nlm.nih.gov/pubmed/17012248?dopt=Abstract

%R 10.1096/fj.06-5800com