Siglec 5 to 11 share a high degree of sequence similarity with CD33/Siglec-3 both in their extracellular and intracellular regions. They are collectively referred to as CD33-related Siglecs. One remarkable feature of the CD33-related Siglecs is their differential expression pattern within the hematopoietic system. This fact, together with the presence of two conserved immunoreceptor tyrosine-based inhibition motifs (ITIMs) in their cytoplasmic tails, suggests that CD33-related Siglecs are involved in the regulation of cellular activation within the immune system. Mouse Siglec-F cDNA encodes a 569 amino acid polypeptide with a hydrophobic signal peptide, an N-terminal Ig-like V-type domain, three Ig-like C2-type domains, a transmembrane region and a cytoplasmic tail. The expression of Siglec-F is restricted to the cells of myelomonocytic lineage. Mouse Siglec-F is likely an ortholog of human Siglec-5. Unlike many human CD33-related Siglecs, which show similar binding to both alpha 2,3- and alpha 2,6-linked sialic acids, mouse Siglec-F preferentially recognize alpha 2,3-linked sialic acid.