Siglecs (sialic acid binding Ig-like lectins) are I-type lectins that belong to the immunoglobulin superfamily. They are characterized by an N-terminal Ig-like V-type domain which mediates sialic acid binding, followed by a varying number of Ig-like C2-type domains. Siglecs 5-11 constitute the CD33/Siglec-3 related group, and are differentially expressed in the hematopoietic system. Siglec-G is the apparent ortholog of human Siglec-10. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains, a transmembrane domain, and a cytoplasmic tail containing two ITIM-signaling motifs. Siglec-10 was identified through database mining of an asthmatic eosinophil EST library. Siglec-10 binds sialated proteins and lipids in alpha 2,3 or alpha 2,6 linkage and shows a preference for GT1b gangliosides. This binding can be modulated by cis interactions of Siglec-10 with sialated molecules expressed on the same cell. When tyrosine phosphorylated, the cytoplasmic ITIMs interact with phosphatases SHP-1 and SHP-2 to propagate inhibitory signals. The Siglec-10-VAP-1 interaction seems to mediate lymphocyte adhesion to endothelium and has the potential to modify the inflammatory microenvironment via the enzymatic end products.
SIGLEC15 (Sialic Acid Binding Ig Like Lectin 15) is a Protein Coding gene. Diseases associated with SIGLEC15 include Osteoporosis, Juvenile and Osteoporosis. Among its related pathways are Innate Immune System and RET signaling. An important paralog of this gene is SIGLEC1.
CD22 is a member of the immunoglobulin superfamily, SIGLEC family of lectins. It is first expressed in the cytoplasm of pro-B and pre-B cells, and on the surface as B cells mature to become IgD+. CD22 serves as an adhesion receptor for sialic acid-bearing ligands expressed on erythrocytes and all leukocyte classes. In addition to its potential role as a mediator of intercellular interactions, signal transduction through CD22 can activate B cells and modulate antigen receptor signaling in vitro. The phenotype of CD22-deficient mice suggests that CD22 is primarily involved in the generation of mature B cells within the bone marrow, blood, and marginal zones of lymphoid tissues. CD22 recruits the tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 (SHP-1) to immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and inhibits B-cell receptor (BCR)-induced Ca2+ signaling on normal B cells. As an inhibitory coreceptor of the B-cell receptor (BCR), CD22 plays a critical role in establishing signalling thresholds for B-cell activation. Like other coreceptors, the ability of CD22 to modulate B-cell signalling is critically dependent upon its proximity to the BCR, and this in turn is governed by the binding of its extracellular domain to alpha2,6-linked sialic acid ligands. However, genetic studies in mice reveal that some CD22 functions are regulated by ligand binding, whereas other functions are ligand-independent and may only require expression of an intact CD22 cytoplasmic domain at the B-cell surface.
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