Dystroglycan is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the DAG1 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...

.

Dystroglycan is one of the dystrophin

Dystrophin

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex...

-associated glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens by chromosome 3. There are two exons that are separated by a large intron

Intron

An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...

. The spliced exons codes for a protein product is finally cleaved into two non-covalently associated subunits, [alpha] (N-terminal) and [beta] (C-terminal).

Function

In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton. [alpha]-dystroglycan is extracellular and binds to merosin [alpha]-2 laminin

Laminin, alpha 2

Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.- Function :Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by...

 in the basement membrane, while [beta]-dystroglycan is a transmembrane protein and binds to dystrophin, which is a large rod-like cytoskeletal protein, absent in Duchenne muscular dystrophy

Duchenne muscular dystrophy

Duchenne muscular dystrophy is a recessive X-linked form of muscular dystrophy, which results in muscle degeneration, difficulty walking, breathing, and death. The incidence is 1 in 3,000 boys. Females and males are affected, though females are rarely affected and are more often carriers...

 patients. Dystrophin binds to intracellular actin

Actin

Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

 cables. In this way, the dystroglycan complex, which links the extracellular matrix to the intracellular actin cables, is thought to provide structural integrity in muscle tissues. The dystroglycan complex is also known to serve as an agrin

Agrin

Agrin is a large proteoglycan whose best characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN...

 receptor in muscle, where it may regulate agrin-induced acetylcholine

Acetylcholine

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 receptor clustering at the neuromuscular junction. There is also evidence which suggests the function of dystroglycan as a part of the signal transduction pathway because it is shown that Grb2

Grb2

Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....

, a mediator of the Ras

Ras

Ras is the name given to a family of related proteins found inside cells, including human cells. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells...

-related signal pathway, can interact with the cytoplasmic domain of dystroglycan.

Expression

Dystroglycan is widely distributed in non-muscle tissues as well as in muscle tissues. During epithelial morphogenesis of kidney, the dystroglycan complex is shown to act as a receptor for the basement membrane. Dystroglycan expression in Mus musculus brain and neural retina has also been reported. However, the physiological role of dystroglycan in non-muscle tissues has remained unclear

Interactions

Dystroglycan has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with FYN

FYN

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...

, C-src tyrosine kinase

C-src tyrosine kinase

C-src tyrosine kinase, also known as CSK, is a human protein and gene. It includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. This protein specifically phosphorylates Tyr-504 residue on human leukocyte-specific protein tyrosine kinase, which acts as a negative regulatory site...

, Src

Src (gene)

Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...

, NCK1

NCK1

Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.-Interactions:NCK1 has been shown to interact with DNM1, EIF2B2, KHDRBS1, Lymphocyte cytosolic protein 2, EPH receptor B1, SOCS7, MINK1, MAP4K1, MAP4K4, Abl gene, WIPF1, RRAS, Wiskott-Aldrich syndrome protein,...

, Grb2

Grb2

Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....

, Caveolin 3

Caveolin 3

Caveolin-3 is a protein that in humans is encoded by the CAV3 gene.-Interactions:Caveolin 3 has been shown to interact with Epidermal growth factor receptor, Dysferlin and Dystroglycan.-Further reading:...

 and SHC1

SHC1

SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells....

.

Further reading

External links

• Overview at sdbonline.org
• http://www.neuro.wustl.edu/neuromuscular/musdist/dag2.htm#ad