CD33 gp67, p67, Siglec-3, My9
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Myeloid Cell
Monocyte
Leukemia cell
Langerhans Cell
Macrophage
Dendritic Cell
Granulocyte
Hematopoietic Progenitor Cell
Myelomonocytic cell
Promyelocyte
Myelocyte
67 / 67
150 / 150

Expression
CD33 is expressed on myeloid lineage cells with decreasing expression on maturation and differentiation  Expression is strong monocytes, macrophages, dendritic cells and Langerhans cells but is weak on polymorphonuclear cells.  Expression is on granulocyte precursors such as promyelocytes and myelocytes but a low level of expression on mature granulocytes.  There is expression on  hematopoietic progenitor cells and is absent on pluripotential stem cells but appears on myelomonocytic precursors after CD34.  CD33 is an important marker for distinguishing myeloid from lymphoid leukemias.

Structure
MOLECULAR FAMILY NAME: Belongs to the sialoadhesin family.

CD33 is a single-pass type-1 364 aa glycoprotein.  It contains a 17 aa signal peptide, a 241 aa extracellular domain which contains a Ig-like V-type domain and a Ig-like C2-type domain and 5 N-glycosylation sites, a 22 aa transmembrane domain and an 81 aa cytoplasmic domain containing 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs).  CD33 is the smallest member of a structurally related group of IgSF domain-containing sialic acid-binding proteins called the sialoadhesin family, which includes sialoadhesin, CD22, and myelin-associated glycoprotein (MAG).  When CD33 was analyzed without reduction, the molecule appears to be a homidimer and monomer on the cell surface.  The amino terminal Ig-like V-type domain interacts with sialic acid but the Ig-like C2-type is also reguired for binding.  Like other members of the sialoadhesion family, CD33 is predicted to have an unusual disulfide bond between b strands B and E in domain 1 and a disulfide bond between domains 1 and 2.  CD33 has 2 cDNA clones which have been isolated in the mouse encoding CD33 isoforms with different cytoplasmic domains.

MOLECULAR MASS
Cell Type Unreduced Reduced
Unspecified 150 kDa 67 kDa

POST-TRANSCRIPTIONAL MODIFICATION

There are 2 mRNA transcripts, ~1,4 and 1.6 kb pairs, anneal to the CD33 probe.  The differences the 2 species has not been reported.

POST-TRANSLATIONAL MODIFICATION

There are 5 consensus sites for addition of N-linked oligasaccharide chains.  Based on differences between the observed and predicted molecular mass and the intensity of metabolic labeling with radioactive sugars, it is predicted that there is a significant degree of glycosylation. 


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD33

CD33 has lectin activity for sugar chains containing sialic acid like N-acetyineuraminic acid -a2,3-galactose.  Like sialoadhesin, CD33 binds to the sialoglycoconjugates NeuAca2 ->3Galb1 ->3(4)GlcNAc and NeuAca2 ->3Galb1 ->3GalNAc on glycoproteins.

Function
The intracellular ITIM sequence of CD33 served as a binding site for Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 that in turn has an inhibitory effect on signal transduction.  CD33 acts as a receptor that inhibits the proliferation of normal and leukemic myeloid cells and may mediate cell-cell adhesion.  Cells expressing CD33 require desialylation before they can bind cells bearing the appropriate sialoglycoconjugate, suggesting that inhibitory cis-interactions may regulate or block any adhesion function.  Although in vivo function is unknown, in vitro studies suggest CD33 plays a negative role in myeloid hematopoiesis.

BIOCHEMICAL ACTIVITY

CD33 is involved in carbohydrate binding and lectin activity.

DISEASE RELEVANCE AND FUNCTION OF CD33 IN INTACT ANIMAL

CD33 is a phenotypic marker in the diagnosis of acute myelogenous leukemia (AML) particularly types M1-5 and induced apoptosis.  CD33 is a target of AML patiensts with a humanized CD33 antibody (Myelotarg) congugated to a cytotoxic drug approved for clinical use.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD33: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD33: No information.

ADDITIONAL INSIGHTS

CD33 has been one of the more enigmatic the leukocyte differentiation antigens.  The program of expression is highly specific to the hematopoietic compartment and shows prominent expression on early myeloid cells and 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 biological role of CD33 remains obsure.  Sequence homology to members of the sialoadhesin family, including myeloid associated glycoprotein and CD22, as well as sialoadhesin itself, led to the demonstration of carbohydrate activity characteristic of this lectin family.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 945P20138
MouseS71345
MouseS71403
Antibodies
HIM3-4   View Reactivity
WM53   View Reactivity

Revised June 25, 2008


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