Siglec-7: a sialic acid-binding lectin of the immunoglobulin superfamily

The Siglecs are a recently discovered family of sialic acid-binding lectins of the immunoglobulin (Ig) superfamily. We report a molecule showing homol ogy to the six first reported Siglecs, with the closest relationship to Sig lec-3(CD33), Siglec-5, and Siglec-6(OBBP-1). The extracellular portion has two Ig-like domains, with the amino-terminal V-set Ig domain including amin o acid residues known to be involved in sialic acid recognition by other Si glecs. The cytoplasmic domain has putative sites of tyrosine phosphorylatio n shared with some Siglecs, including an Immunoreceptor Tyrosine-based Inhi bitory Motif (ITIM). Expression of the full-length cDNA induces sialic acid -dependent binding to human erythrocytes. A recombinant chimeric form conta ining the extracellular Ig domains selectively recognizes the sequence NeuS Ac alpha 2-6Gal beta 1-4Glc, and binding requires the side chain of sialic acid. Mutation of an arginine residue predicted to be critical for sialic a cid binding abolishes both interactions. Taken together, our findings justi fy designation of the molecule as Siglec-7. Analysis of bacterial artificia l chromosome (BAC) clones spanning the known human genomic location of Sigl ec-3 indicates that the Siglec-7 gene is also located on chromosome 19q13.3 -13.4. Human tissues show strong expression of Siglec-7 mRNA in spleen, per ipheral blood leukocytes, and liver. The combination of an extracellular si alic acid binding site and an intracellular ITIM motif suggests that this m olecule is involved in trans-membrane regulatory signaling reactions.