Siglec-15: an immune system Siglec conserved throughout vertebrate evolution

Glycobiology. 2007 Aug;17(8):838-46. doi: 10.1093/glycob/cwm049. Epub 2007 May 4.


Siglecs are vertebrate cell-surface receptors that recognize sialylated glycans. Here we have identified and characterized a novel Siglec, named Siglec-15. Siglec-15 is a type-I transmembrane protein consisting of: (i) two immunoglobulin (Ig)-like domains, (ii) a transmembrane domain containing a lysine residue, and (iii) a short cytoplasmic tail. Siglec-15 is expressed on macrophages and/or dendritic cells of human spleen and lymph nodes. We show that the extracellular domain of Siglec-15 preferentially recognizes the Neu5Acalpha2-6GalNAcalpha- structure. Siglec-15 associates with the activating adaptor proteins DNAX activation protein (DAP)12 and DAP10 via its lysine residue in the transmembrane domain, implying that it functions as an activating signaling molecule. Siglec-15 is the second human Siglec identified to have an activating signaling potential; unlike Siglec-14, however, it does not have an inhibitory counterpart. Orthologs of Siglec-15 are present not only in mammals but also in other branches of vertebrates; in contrast, no other known Siglec expressed in the immune system has been conserved throughout vertebrate evolution. Thus, Siglec-15 probably plays a conserved, regulatory role in the immune system of vertebrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • Evolution, Molecular*
  • Humans
  • Immune System / immunology*
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism*
  • Lectins / genetics*
  • Lectins / metabolism*
  • Ligands
  • Lymph Nodes / immunology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Phylogeny
  • Receptors, Immunologic / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Spleen / immunology


  • Adaptor Proteins, Signal Transducing
  • HCST protein, human
  • Immunoglobulins
  • Lectins
  • Ligands
  • Membrane Proteins
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Siglec-15 protein, human
  • TYROBP protein, human