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FASEB J. 2006 Oct;20(12):1964-73.

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

Author information

1
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan. takashi-angata@aist.go.jp

Abstract

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.

PMID:
17012248
DOI:
10.1096/fj.06-5800com
[Indexed for MEDLINE]
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