PROW Guide: CD33

CD33
Author: Stephen Peiper
Reviewer: James D. Griffin
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OVERVIEW Molecular Families

CD33 has been one of the more enigmatic of the leukocyte differentiation antigens
The program of expression of CD33 is highly specific to the hematopoietic compartment and shows prominent expression on early myeloid cells
Expression of CD33 is a feature of 'multipotential' hematopoietic stem cells, but not 'true stem cells'. In addition, anti-CD33 monoclonal antibodies are highly valuable immunologic reagents for distinguishing acute myeloid leukemias from their lymphoblastic counterparts*
Despite these novel features and molecular cloning of the gene, the biologic role of CD33 remains obscure
Sequence homology to members of the sialoadhesin family, including myelin-associated glycoprotein and CD22, as well as sialoadhesin, itself, led to the demonstration of carbohydrate binding activity characteristic of this lectin family
The CD33 genomic locus has been mapped to chromosome 19q13.1-3, similar to that of myelin associated glycoprotein, which shares similarities of structure and function
The recent cloning of the murine CD33 homolog should empower gene targeting experiments to elucidate the function of this differentiation antigen in null homozygous mice

SYSTEM VIEW Disease Relevance / Function in Vivo

Myeloid progenitors (CFU-GEMM, CFU-GM, CFU-G, BFU-E)
Monocytes/Macrophages
Granulocyte precursors (promyelocytes, myelocytes etc, decreasing expression with maturation and differentiation)
Mature granulocytes (low level expression)
No known expression outside of the hematopoietic system**

GENE Gene Sequence Links

TRANSCRIPT Transcript Sequence Links

Two mRNA transcripts (approximately 1.4 and 1.6 kilobase pairs) anneal to the CD33 probe. The differences between these two species have not been reported

PROTEIN Biochemical Activity

CD33 is a glycoprotein composed of 364 amino acids
Signal peptide (aa 1-17)
Extracellular region of 241 residues that includes and IgV domain (aa 18-121) and an IgC2 type domain (aa 156-219)
Transmembrane spanning domain (aa 260-282)
Cytoplasmic tail (aa 283-364)
When analyzed without reduction, the molecule appears to be a homodimer

Cell_Type	MW_unreduced	MW_reduced	Comment
Unspecified	150 kDa	67 kDa

There are five consensus sites for addition of N-linked oligosaccharide chains. Based on the differences between the observed and predicted molecular mass and the intensity of metabolic labeling with radioactive sugars, it is projected that there is a significant degree of glycosylation