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

Takashi Angata, Toshiyuki Hayakawa, Masahiro Yamanaka, Ajit Varki, Mitsuru Nakamura

Research output: Contribution to journalArticlepeer-review

135 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1964-1973
Number of pages10
JournalFASEB Journal
Issue number12
Publication statusPublished - Oct 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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