CD33 or Siglec-3 (sialic acid-binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a transmembrane receptor expressed on myeloid cells. It is commonly considered to be bone marrow-specific but can also be found on some lymphoid cells. It binds to sialic acid, thus being a member of the SIGLEC lectin family.
The extracellular portion of this receptor contains two immunoglobulin-like domains (one IgV and one IgC2 domain), placing CD33 within the immunoglobulin superfamily. The intracellular part of CD33 contains an inhibitory motif based on immunoreceptor tyrosine-based inhibition (ITIM), which is associated with inhibiting cell activity.
CD33 can be stimulated by any molecule carrying sialic acid residues, such as glycoproteins or glycolipids. Upon binding, the ITIM-based inhibition motif of CD33, located in the cytoplasmic part of the protein, is phosphorylated and serves as a docking site for proteins containing Src homology 2 (SH2) domains (like SHP phosphatase). This results in a cascade reaction inhibiting cell phagocytosis.
