CD33

CD33 Full Name

CD33 molecule

CD33 Introduction

CD33, also known as Siglec-3, is a transmembrane glycoprotein that plays a crucial role in immune regulation. As a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family, CD33 is primarily expressed on cells of the myeloid lineage and functions as an inhibitory receptor that modulates immune responses. This gene has garnered significant research attention due to its clinical relevance in acute myeloid leukemia (AML) and its genetic association with Alzheimer's disease susceptibility.

Figure 1. Strcuture of CD33 molecule.

Genomic Characteristics and Protein Structure
The CD33 gene is located on chromosome 19 (19q13.33) and consists of seven exons that encode a 67 kDa transmembrane protein. The mature CD33 protein comprises four distinct structural regions: an N-terminal signal peptide, two extracellular immunoglobulin-like domains (including a V-set domain that mediates sialic acid binding), a transmembrane region, and a cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences.

These ITIM sequences are critical for CD33's inhibitory function. Upon ligand binding, tyrosine residues within these motifs become phosphorylated, recruiting protein tyrosine phosphatases SHP-1 and SHP-2. These phosphatases subsequently dephosphorylate signaling molecules, effectively dampening cellular activation.

Biological Function
CD33 functions primarily as an inhibitory receptor within the myeloid compartment. Through its recognition of sialic acid-containing glycans—preferentially α-2,6-linked sialic acids—CD33 mediates cell-cell interactions and helps maintain immune cells in a resting state. The inhibitory signal is transduced via the ITIM motifs in its cytoplasmic domain, which recruit phosphatases that suppress activation pathways. This inhibitory function appears to regulate multiple processes, including cytokine production, monocyte activation, and phagocytic activity. Studies using CD33 knockdown in human monocytes have demonstrated elevated cytokine production, confirming its role as an immune checkpoint molecule.

Alternate Names for CD33

CD33; CD33 molecule; p67; SIGLEC3; SIGLEC-3; myeloid cell surface antigen CD33; gp67; CD33 antigen (gp67); sialic acid binding Ig-like lectin 3; sialic acid-binding Ig-like lectin 3;