Gamma-sarcoglycan is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''SGCG''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
The α to δ-sarcoglycans are expressed predominantly (β) or exclusively (α, γ and δ) in
striated muscle
Striations means a series of ridges, furrows or linear marks, and is used in several ways:
* Glacial striation
* Striation (fatigue), in material
* Striation (geology), a ''striation'' as a result of a geological fault
* Striation Valley, in An ...
.
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 replication, DNA or viral repl ...
in any of the
sarcoglycan
The sarcoglycans are a family of transmembrane proteins (α, β, γ, δ or ε) involved in the protein complex responsible for connecting the muscle fibre cytoskeleton to the extracellular matrix, preventing damage to the muscle fibre sarcolemma t ...
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 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 com ...
to the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...
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 cost ...
, 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
Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 114 million base pairs (the building material of DNA) and represents between 3.5 and 4% of the total DNA ...
at q12, spans over 100 kb of DNA and includes 8
exons.
Protein
Gamma-sarcoglycan is a type II
transmembrane protein
A transmembrane protein (TP) 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 frequent ...
and consists of 291
amino acids. 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.
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 (; ar, الْمَغْرِب, al-Maghrib, lit=the west), also known as the Arab Maghreb ( ar, المغرب العربي) and Northwest Africa, is the western part of North Africa and the Arab world. The region includes Algeria, ...
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
The Romani (also spelled Romany or Rromani , ), colloquially known as the Roma, are an Indo-Aryan ethnic group, traditionally nomadic itinerants. They live in Europe and Anatolia, and have diaspora populations located worldwide, with sign ...
population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.
Interactions
SGCG has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
FLNC
The National Liberation Front of Corsica ( co, Fronte di liberazione naziunale di a Corsica or ; french: Front de libération nationale corse, abbreviated FLNC) was a militant group that advocates an independent state on the island of Corsica, s ...
.
References
Further reading
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External links
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LOVD The Leiden Open Variation Database (LOVD) is a free, flexible web-based open source database developed in the Leiden University Medical Center in the Netherlands, designed to collect and display variants in the DNA sequence. The focus of an LOVD i ...
mutation database
SGCG
{{Muscle tissue