Dystrobrevin is a protein that binds to dystrophin in the costamere of skeletal muscle cells. In humans, there are at least two isoforms of dystrobrevin, dystrobrevin alpha and dystrobrevin beta. Dystrobrevins are members of dystrophin-related protein family which are thought to play an important role in intracellular signal transduction and provide a membrane scaffold in muscle. Defects in dystrobrevins and their associated proteins cause a range of neuromuscular diseases such as muscular dystrophies. Dystrobrevin was first identified by isolating from the electric organ of the electric ray Torpedo californica. It is a phosphoprotein, which weights 87 kDa, associated with the postsynaptic membrane at the cytoplasmic face. Dystrobrevin proteins have been said to participates in the formation and stability of synapses because it copurifies with acetylcholine receptors from Torpedo electric organ membranes. In 1997, an experiment was done using the yeast two-hybrid model to identify protein-protein interaction between dystrobrevin and dystrophin-associated protein complex (DPC). The evidence suggested that dystrobrevin works as a motor protein receptor that might play an important role in the transport of components of the dystrophin-associated protein complex to specific intracellular sites. The DPC is expressed in both muscle and non-muscle tissues. It works as a mechanical component of cells and a dynamic multifunctional structure that can serve as a scaffold for signaling molecules. The dystrophin-associated proteins can be divided into three groups depending on their cellular localization: extracellular, transmembrane, and cytoplasmic. Dystrobrevin protein is a part of the cytoplasmic complex and an intracellular protein that binds directly to dystrophin. In invertebrates, dystrobrevin is present as a single protein, while in vertebrates, there are two isoforms, a-dystrobrevin (DTNA) and β-dystrobrevin (DTNB). Each dystrobrevin isoform has a unique structure with carboxyl termini and sequence homology with the cysteine-rich carboxyl-terminal region of dystrophin. This region of similarity can be divided into several functional domains such as two coiled-coil regions, two EF hands or a ZZ-type zinc finger. Evolutionary History A phylogenic tree for the dystrophin protein family has been proposed based on the analysis of known dystrobrevin and dystrophin sequences that were extracted from human and fruit fly proteins. The phylogeny postulated a non-metazoan ancestor that had a single dystrophin/dystrobrevin protein, which probably functioned as a homodimer. At some point before the last common ancestor of metazoans, a duplication lead to a separation of dystrophin and dystrobrevin genes, their protein products forming a heterodimer of more specialized components. In vertebrates,