CD38 also known as cyclic ADP ribose hydrolase is a glycoprotein

Glycoprotein

Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 found on the surface of many immune cells (white blood cell

White blood cell

White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

s), including CD4

CD4

CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...

⁺, CD8

CD8

CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...

⁺, B and natural killer cell

Natural killer cell

Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...

s. CD38 also functions in cell adhesion

Cell adhesion

Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...

, signal transduction

Signal transduction

Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 and calcium signaling

Calcium signaling

Calcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins...

.

In humans, the CD38 protein is encoded by the CD38 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 which located on chromosome 4

Chromosome 4 (human)

125px|rightChromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs and represents between 6 and 6.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area...

.

Function

CD38 is a multifunctional ectoenzyme

Ectonucleotidase

Ectonucleotidases consist of families of nucleotide metabolizing enzymes that are expressed on the plasma membrane and have externally orientated active sites. These ectoenzymes operate in concert or consecutively and metabolize nucleotides to the respective nucleoside analogs. They have the...

 that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose

Cyclic ADP-ribose

Cyclic ADP Ribose, frequently abbreviated as cADPR, is a cyclic adenine nucleotide with two phosphate groups present on 5' OH of the adenosine , further connected to another ribose at the 5' position, which, in turn, closes the cycle by glycosidic bonding to the nitrogen 1 of the same adenine...

 (cADPR) from NAD⁺

Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...

 to ADP-ribose

Adenosine diphosphate ribose

Adenosine diphosphate ribose is a molecule formed into chains by the enzyme poly ADP ribose polymerase. It binds to and activates the TRPM2 ion channel....

. These reaction products are essential for the regulation of intracellular Ca²⁺.

Clinical significance

The loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications.

The CD38 protein is a marker of cell activation. It has been connected to HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

 infection, leukemia

Leukemia

Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

s, myelomas, solid tumors, type II diabetes mellitus and bone metabolism, as well as some genetically determined conditions.

Application

CD38 has been used as a prognostic marker in leukemia

Leukemia

Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

. It can also be used to identify plasma cell

Plasma cell

Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...

s.

Further reading

External links