CD38 (cluster of differentiation 38), previously known as T10, is a 46 kDa type II transmembrane glycoprotein (1). CD38 is expressed in both lymphoid and non-lymphoid tissue including in thymocytes, T and B lymphocytes, myeloid cells, natural killer cells, plasma cells, erythrocytes, and additionally in cells of the brain, pancreas, muscle, and bone (1,2). Structurally, CD38 is an "L"-shape which is formed by two separate domains connected by a three peptide-chain hinge region (2). The N-terminal domain is composed of five alpha-helices and two beta strands, while the C-terminal domain contains a four-stranded parallel beta-sheet and two long and two short alpha-helices (2). The CD38 molecule is located on chromosome 4 and is 300 amino acids (aa) in length with a theoretical molecular weight of 34 kDa that functions as both a receptor and an enzyme (1-6). As a receptor, CD38 interacts with its ligand CD31, which is largely expressed in endothelial cells (2-6). As an ectoenzyme, CD38 has a role in calcium signaling and is responsible for the conversion of nicotinamide adenine dinucleotide (NAD) into adenosine diphosphate-ribose (ADPR) or cyclic ADPR and the conversion of phosphorylated NAD (NADP) into nicotinic acid adenine dinucleotide phosphate (NAADP) (2-6).

As described above, CD38 is highly expressed in plasma cells and, as a result, is a target for treating multiple myeloma (MM), the cancer of white blood cells (4,6). The anti-CD38 monoclonal antibody daratumumab is one specific treatment for MM (4,6). Daratumumab has been shown to target MM cells through antibody-dependent cellular cytotoxicity and antibody dependent cellular phagocytosis (4). Additionally, CD38 has a potential role in neurodegenerative disorders and neuroinflammation as elucidated CD38's high expression in neurons, astrocytes, and microglia along with its enzymatic role in NAD degradation (3). Reduced NAD levels is a consequence of aging and occurs during neurodegeneration (3). Furthermore, murine studies have found that CD38 deletion inhibits neuroinflammation and neurodegeneration and therefore might be a potential therapeutic target (3). Similarly, CD38 inhibitors, like quercetin and luteolin, are used to treat age-related diseases and metabolic disorders (7).

References

1. Malavasi, F., Funaro, A., Alessio, M., DeMonte, L. B., Ausiello, C. M., Dianzani, U., Lanza, F., Magrini, E., Momo, M., & Roggero, S. (1992). CD38: a multi-lineage cell activation molecule with a split personality. International journal of clinical & laboratory research. https://doi.org/10.1007/BF02591400

2. Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A. L., Ortolan, E., Vaisitti, T., & Aydin, S. (2008). Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiological reviews. https://doi.org/10.1152/physrev.00035.2007

3. Guerreiro, S., Privat, A. L., Bressac, L., & Toulorge, D. (2020). CD38 in Neurodegeneration and Neuroinflammation. Cells. https://doi.org/10.3390/cells9020471

4. van de Donk, N., Richardson, P. G., & Malavasi, F. (2018). CD38 antibodies in multiple myeloma: back to the future. Blood. https://doi.org/10.1182/blood-2017-06-740944

5. Lund, F. E., Cockayne, D. A., Randall, T. D., Solvason, N., Schuber, F., & Howard, M. C. (1998). CD38: a new paradigm in lymphocyte activation and signal transduction. Immunological reviews. https://doi.org/10.1111/j.1600-065x.1998.tb01573.x

6. Glaria, E., & Valledor, A. F. (2020). Roles of CD38 in the Immune Response to Infection. Cells. https://doi.org/10.3390/cells9010228

7. Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell metabolism. https://doi.org/10.1016/j.cmet.2018.02.011

Long Name

Cluster of Differentiation 38

Alternate Names

ADP-ribosyl Cyclase, CD38, Cyclic ADP-ribose Hydrolase

Gene Symbol

CD38

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Product Specific Notices for CD38 Antibody (rCD38/8334) [Janelia Fluor® 585]

Sold under license from the Howard Hughes Medical Institute, Janelia Research Campus.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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CD38 Antibody (rCD38/8334) [Janelia Fluor® 585]

Novus Biologicals, part of Bio-Techne | Catalog # NBP3-23981JF585

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Background: CD38