CD33
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 5IHB, 5J06, 5J0B, 6D48, 6D49, 6D4A, 6TL8, 7AW6
Identifiers
Aliases	CD33, CD33 molecule, SIGLEC-3, SIGLEC3, p67
External IDs	OMIM: 159590 HomoloGene: 88651 GeneCards: CD33
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.41 Start 51,225,064 bp[1] End 51,243,860 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte spleen blood bone marrow cells right coronary artery upper lobe of left lung right lung appendix gallbladder lymph node n/a More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding carbohydrate binding signaling receptor activity protein phosphatase binding sialic acid binding Cellular component integral component of membrane integral component of plasma membrane membrane external side of plasma membrane nucleus plasma membrane specific granule membrane tertiary granule membrane peroxisome Golgi apparatus Biological process cell-cell signaling cell adhesion signal transduction negative regulation of cell population proliferation regulation of immune response neutrophil degranulation immune response-inhibiting signal transduction positive regulation of protein secretion negative regulation of interleukin-1 beta production negative regulation of interleukin-8 production negative regulation of tumor necrosis factor production negative regulation of calcium ion transport cell-cell adhesion positive regulation of protein tyrosine phosphatase activity negative regulation of monocyte activation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 945 n/a Ensembl ENSG00000105383 n/a UniProt P20138 n/a RefSeq (mRNA) NM_001082618 NM_001177608 NM_001772 n/a RefSeq (protein) NP_001076087 NP_001171079 NP_001763 n/a Location (UCSC) Chr 19: 51.23 – 51.24 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

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.^[3] It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.^[4]

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.^[5]

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.^[6]

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.^{[7][8][9][10]}

Clinical significance

CD33 is the target of gemtuzumab ozogamicin (trade name: Mylotarg®; Pfizer/Wyeth-Ayerst Laboratories),^[11] an antibody-drug conjugate (ADC) for the treatment of patients with acute myeloid leukemia. The drug is a recombinant, humanized anti-CD33 monoclonal antibody (IgG4 κ antibody hP67.6) covalently attached to the cytotoxic antitumor antibiotic calicheamicin (N-acetyl-γ-calicheamicin) via a bifunctional linker (4-(4-acetylphenoxy)butanoic acid).^[12] Several mechanisms of resistance to gemtuzumab ozogamicin have been elucidated.^[13] On September 1, 2017, the FDA approved Pfizer's Mylotarg.^[14]

Gemtuzumab ozogamicin was initially approved by the U.S. Food and Drug Administration in 2000. However, during post marketing clinical trials researchers noticed a greater number of deaths in the group of patients who received gemtuzumab ozogamicin compared with those receiving chemotherapy alone. Based on these results, Pfizer voluntarily withdrew gemtuzumab ozogamicin from the market in mid-2010, but was reintroduced to the market in 2017.^[15][16][17]

CD33 is also the target in Vadastuximab talirine (SGN-CD33A), a novel antibody-drug conjugate being developed by Seattle Genetics, utilizing this company's ADC technology.^[18]