Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state ( ). Preferentially recognizes and binds alpha-2,3- and more avidly alpha-2,6-linked sialic acid-bearing glycans . Upon engagement of ligands such as C1q or syalylated glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in CD33 cytoplasmic tail are phosphorylated by Src-like kinases such as LCK (, ). These phosphorylations provide docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 ( ). In turn, these phosphatases regulate downstream pathways through dephosphorylation of signaling molecules (, ). One of the repressive effect of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K .
Subcellular locations: Cell membrane
Subcellular locations: Peroxisome
CD33m isoform does not localize to cell surfaces but instead accumulates in peroxisomes.
Monocytic/myeloid lineage cells. In the brain, CD33 is mainly expressed on microglial cells.