CD33: The Myeloid-Specific Sialic Acid Binding Receptor
CD33, also known as SIGLEC-3 (sialic acid binding Ig-like lectin 3), is a specialized transmembrane receptor primarily expressed on cells of the myeloid lineage. While it is widely regarded as myeloid-specific, it can also be detected on certain lymphoid cells. As a member of the SIGLEC family of lectins, its primary biochemical characteristic is its ability to bind to sialic acids, which are sugar molecules found on the surface of many cell types.
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Key Facts
- Primary Function: Acts as a signaling receptor that binds sialic acids to modulate immune responses.
- Cellular Expression: Predominantly found in monocytes and granulocytes.
- Genetic Location: Located on Chromosome 19 (19q13.41) in humans and Chromosome 7 in mice.
- Biological Role: Involved in the negative regulation of cell proliferation and the inhibition of various pro-inflammatory cytokines.
- Family: Part of the SIGLEC (Sialic acid-binding immunoglobulin-type lectins) family.
Molecular Structure and Genetic Mapping
The CD33 molecule, sometimes referred to as p67 or gp67, is encoded by genes located at specific chromosomal bands. In humans, the gene is situated on Chromosome 19 at band 19q13.41, spanning from 51,225,064 to 51,243,860 base pairs (bp). In mice, the ortholog is located on Chromosome 7 at band 7 B3, spanning 43,173,640 to 43,193,852 bp.
Structurally, CD33 is an integral component of the plasma membrane, specifically positioned on the external side. It is also associated with the Golgi apparatus, peroxisomes, and specific granule membranes, including tertiary granule membranes.
Protein Data and Identifiers
Researchers utilize several identifiers to track CD33 across different databases. It is cataloged under OMIM 159590 and MGI 99440. Multiple protein structures have been solved and deposited in the Protein Data Bank (PDB), including codes such as 5IHB, 5J06, 6D48, and 7AW6.
Biological Functions and Expression Patterns
CD33 plays a critical role in signal transduction and cell-cell signaling. Its molecular functions include protein binding, carbohydrate binding, and protein phosphatase binding. By acting as a signaling receptor, it helps regulate the immune system's intensity.
Tissue Expression
The expression of CD33 is highly concentrated in the hematopoietic system. In humans, the highest expression levels are found in:
- Monocytes and granulocytes
- Bone marrow cells and blood
- The spleen
- Specific tissues including the right coronary artery, right lung, upper lobe of the left lung, appendix, and right adrenal cortex.
In mice, expression is similarly prominent in granulocytes, blood, and the spleen, but also extends to the stroma of the bone marrow, the submandibular gland, and the superior frontal gyrus.
Regulation of the Immune Response
CD33 is primarily involved in the negative regulation of the immune response. It inhibits the production of several key pro-inflammatory markers, including:
- Interleukin-1 beta (IL-1β)
- Interleukin-8 (IL-8)
- Tumor necrosis factor (TNF)
Additionally, it is involved in neutrophil degranulation, the negative regulation of monocyte activation, and the positive regulation of protein tyrosine phosphatase activity.
Summary of CD33 Characteristics
| Feature | Human Details | Mouse Details |
|---|---|---|
| Gene Location | Chr 19 (19q13.41) | Chr 7 (7 B3) |
| UniProt ID | P20138 | Q63994 |
| Primary Cell Types | Monocytes, Granulocytes | Granulocytes, Bone marrow stroma |
| Main Ligand | Sialic acids | Sialic acids |
| Key Function | Immune inhibition | Immune inhibition |
Frequently Asked Questions
What is CD33?
CD33, or SIGLEC-3, is a transmembrane receptor found mainly on myeloid cells. It belongs to the SIGLEC family of lectins and is characterized by its ability to bind sialic acids on cell surfaces.
Which cells express CD33?
It is primarily expressed on cells of the myeloid lineage, such as monocytes and granulocytes, although it can occasionally be found on some lymphoid cells.
What is the primary biological role of CD33?
CD33 generally acts as an inhibitor of the immune response. It negatively regulates the production of pro-inflammatory cytokines like TNF, IL-1β, and IL-8, and inhibits monocyte activation.
Where is the CD33 gene located in humans?
In humans, the CD33 gene is located on Chromosome 19 at the band 19q13.41.
What are the molecular functions of CD33?
Its molecular functions include carbohydrate binding (specifically sialic acid), protein binding, signaling receptor activity, and protein phosphatase binding.