HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Angata, T. Articles by Nakamura, M. Search for Related Content PubMed PubMed Citation Articles by Angata, T. Articles by Nakamura, M.

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

Takashi Angata^*,1,2, Toshiyuki Hayakawa^,1,3, Masahiro Yamanaka^*, Ajit Varki and Mitsuru Nakamura^*

^* Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan; and

Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, USA

²Correspondence: Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, 1–1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan. E-mail: takashi-angata{at}aist.go.jp

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.—Angata, T., Hayakawa, T., Yamanaka, M., Varki, A., Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates.

Key Words: innate immunity • paired receptors • gene conversion • DAP12 • great apes

This article has been cited by other articles:

				P. Gunnarsson, L. Levander, P. Pahlsson, and M. Grenegard The acute-phase protein {alpha}1-acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin-like lectins (Siglecs) FASEB J, December 1, 2007; 21(14): 4059 - 4069. [Abstract] [Full Text] [PDF]

				T. Angata, Y. Tabuchi, K. Nakamura, and M. Nakamura Siglec-15: an immune system Siglec conserved throughout vertebrate evolution Glycobiology, August 1, 2007; 17(8): 838 - 846. [Abstract] [Full Text] [PDF]