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 (PubMed:10611343, PubMed:15597323, PubMed:11320212). Preferentially recognizes and binds alpha-2,3- and more avidly alpha-2,6-linked sialic acid-bearing glycans (PubMed:7718872). 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 (PubMed:28325905, PubMed:10887109). These phosphorylations provide docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:10556798, PubMed:10206955, PubMed:10887109). In turn, these phosphatases regulate downstream pathways through dephosphorylation of signaling molecules (PubMed:10206955, PubMed:10887109). One of the repressive effect of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K (PubMed:15597323). Homodimer; disulfide-linked (PubMed:10887109). Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation (PubMed:10556798, PubMed:10206955). Interacts with C1QA (via C-terminus); this interaction activates CD33 inhibitory motifs (PubMed:28325905). 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. Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Glycosylated. Glycosylation at Asn-100 is critical for regulating ligand recognition. Phosphorylation of Tyr-340 is involved in binding to PTPN6 and PTPN11. Phosphorylation of Tyr-358 is involved in binding to PTPN6. LCK phosphorylates Tyr-340 efficiently and Tyr-358 to a lesser extent. Mostly detected on NKL and myeloid cell lines but poorly expressed on B-cell lines and T-lymphocytes. Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family. Siglec-3