Gamma-sarcoglycan 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 ''SGCG''
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 ...
.
The α to δ-sarcoglycans are expressed predominantly (β) or exclusively (α, γ and δ) in
striated muscle.
A
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
in any of the
sarcoglycan genes may lead to a secondary deficiency of the other sarcoglycan proteins, presumably due to destabilisation of the sarcoglycan complex.
The disease-causing mutations in the α to δ genes cause disruptions within the
dystrophin-associated protein (DAP) complex in the
muscle cell
A muscle cell, also known as a myocyte, is a mature contractile Cell (biology), cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal muscle, skeletal, smooth muscle, smooth, and Cardiac muscle, cardiac ...
membrane.
The transmembrane components of the DAP complex link the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
to the
extracellular matrix in adult
muscle fibres,
and are essential for the preservation of the integrity of the muscle cell membrane.
Function
Gamma-sarcoglycan is one of several sarcolemmal transmembrane glycoproteins that interact with
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 ...
, probably to provide a link between the membrane associated cytoskeleton and the extracellular matrix. Defects in the protein can lead to early onset autosomal recessive muscular dystrophy, in particular
limb-girdle muscular dystrophy, type 2C (LGMD2C).
Structure
Gene
Human SGCG gene maps to
chromosome 13 at q12, spans over 100 kb of DNA and includes 8
exons.
Protein
Gamma-sarcoglycan is a type II
transmembrane protein
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 un ...
and consists of 291
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
. It has a 35 amino acid intracellular
N-terminal region, a 25 amino acid single transmembrane domain, and a 231 amino acid extra-cellular
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein
Proteins are large biomolecules and macromolecules that comp ...
.
Clinical significance
Sarcoglycanopathies are autosomal recessive
limb girdle muscular dystrophies (LGMDs) caused by mutations in any of the four sarcoglycan genes: α (LGMD2D), β (LGMD2E), γ (LGMD2C) and δ (LGMD2F).
Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder that segregates with microsatellite markers at γ-sarcoglycan gene. Mutations in the γ-sarcoglycan gene were first described in the
Maghreb
The Maghreb (; ), also known as the Arab Maghreb () and Northwest Africa, is the western part of the Arab world. The region comprises western and central North Africa, including Algeria, Libya, Mauritania, Morocco, and Tunisia. The Maghreb al ...
countries of North Africa,
where γ-sarcoglycanopathy has a higher than usual incidence. One common mutation, Δ-521T, which causes a severe phenotype, occurs both in the Maghreb population and in other countries.
A Cys283Tyr mutation has been identified in the
Gypsy population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.
Interactions
SGCG has been shown to
interact with
FLNC.
References
Further reading
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External links
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LOVD mutation database
SGCG
{{Muscle tissue