CD33
Description
The CD33 (CD33 molecule) is a protein-coding gene located on chromosome 19.
CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells. It binds sialic acids, therefore is a member of the SIGLEC family of lectins.
== Structure == The extracellular portion of this receptor contains two immunoglobulin domains (one IgV and one IgC2 domain), placing CD33 within the immunoglobulin superfamily. The intracellular portion of CD33 contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that are implicated in inhibition of cellular activity.
== Function == CD33 can be stimulated by any molecule with sialic acid residues such as glycoproteins or glycolipids. Upon binding, the immunoreceptor tyrosine-based inhibition motif (ITIM) of CD33, present on the cytosolic portion of the protein, is phosphorylated and acts as a docking site for Src homology 2 (SH2) domain-containing proteins like SHP phosphatases. This results in a cascade that inhibits phagocytosis in the cell.
== Alzheimer's disease == CD33 controls microglial activation but in Alzheimer disease it goes overdrive in presence of amyloid and tau proteins, its expression is known to be tied to TREM2.
== Clinical significance == CD33 is the target of gemtuzumab ozogamicin (trade name: Mylotarg®; Pfizer/Wyeth-Ayerst Laboratories), an antibody-drug conjugate (ADC) for the treatment of patients with acute myeloid leukemia.
CD33, also known as Siglec-3, is a sialic acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and maintaining immune cells in a resting state. CD33 preferentially binds to alpha-2,3-linked and more avidly to alpha-2,6-linked sialic acid-bearing glycans. Upon binding to ligands like C1q or sialylated glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in the cytoplasmic tail of CD33 are phosphorylated by Src-like kinases such as LCK. These phosphorylations act as docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. These phosphatases then regulate downstream pathways by dephosphorylating signaling molecules. One of the repressive effects of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K.
CD33 is also known as CD33rSiglec, SIGLEC-3, SIGLEC3, p67.
