Dystroglycan is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''DAG1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Dystroglycan is one of the
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 costa ...
-associated
glycoproteins
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
, which is encoded by a 5.5 kb transcript in ''
Homo sapiens
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
'' on
chromosome 3
Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...
.
There are two
exons
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...
that are separated by a large
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
. The spliced exons code for a protein product that is finally cleaved into two non-covalently associated subunits,
lpha(N-terminal) and
eta
Eta ( ; uppercase , lowercase ; ''ē̂ta'' or ''ita'' ) is the seventh letter of the Greek alphabet, representing the close front unrounded vowel, . Originally denoting the voiceless glottal fricative, , in most dialects of Ancient Greek, it ...
(C-terminal).
Function
In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton.
lphadystroglycan is extracellular and binds to merosin
lpha2 laminin in the basement membrane, while
eta
Eta ( ; uppercase , lowercase ; ''ē̂ta'' or ''ita'' ) is the seventh letter of the Greek alphabet, representing the close front unrounded vowel, . Originally denoting the voiceless glottal fricative, , in most dialects of Ancient Greek, it ...
dystroglycan is a
transmembrane
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
protein and binds to dystrophin, which is a large rod-like
cytoskeletal
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...
protein, absent in
Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pe ...
patients. Dystrophin binds to intracellular
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
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 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 synaptogenesi ...
receptor in muscle, where it may regulate agrin-induced
acetylcholine
Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
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
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.
The protein encoded by this gene binds recepto ...
, a mediator of the
Ras-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 remains unclear.
In December 2022, the implications of abnormal dystroglycan expression and/or ''O''-mannosylation on the pathogenesis of cancer have been reviewed.
Interactions
Dystroglycan has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
FYN
Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded by the ''FYN'' gene.
Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neurona ...
,
C-src tyrosine kinase
Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HC ...
,
[ Src,][ ]NCK1
Cytoplasmic protein NCK1 is a protein that in humans is encoded by the ''NCK1'' gene.
Gene
The Nck (non-catalytic region of tyrosine kinase adaptor protein 1) belongs to the adaptor family of proteins. The nck gene was initially isolated fro ...
,[ ]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.
The protein encoded by this gene binds recepto ...
,Caveolin 3
Caveolin-3 is a protein that in humans is encoded by the ''CAV3'' gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites ...
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.
SCOP
A ( or ) was a poet as represented in Old ...
.[
]
See also
* Dystrophin-associated protein complex The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up ...
* Actin-binding protein Actin-binding proteins (also known as ABPs) are proteins that bind to actin. This may mean ability to bind actin monomers, or polymers, or both.
Many actin-binding proteins, including α-actinin, β-spectrin, dystrophin, utrophin and fimbrin, do t ...
* 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 synaptogenesi ...
References
Further reading
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External links
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Overview at sdbonline.org
{{Muscle tissue
Glycoproteins
Single-pass transmembrane proteins