GM2 ganglioside activator also known as GM2A is a
protein which in humans is encoded by the ''GM2A''
gene.
Function
The protein encoded by this gene is a small glycolipid transport protein which acts as a substrate specific co-factor for the
lysosomal
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pro ...
enzyme
β-hexosaminidase A. β-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the
ganglioside GM2, and other molecules containing terminal N-acetyl
hexosamines.
GM2A is a lipid transfer protein that stimulates the enzymatic processing of
gangliosides
A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate sia ...
, and also
T-cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
activation through lipid presentation. This protein binds molecules of
ganglioside
A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate ...
GM2, extracts them from membranes, and presents them to beta-
hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3.
It was identified as a member of
ML domain family of proteins involved in
innate immunity
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
and
lipid metabolism
Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In anim ...
in the
SMART database.
Regulation
In melanocytic cells GM2A gene expression may be regulated by
Microphthalmia-associated transcription factor, MITF.
Clinical significance
Mutations in this gene, inherited in an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
pattern, result in
GM2-gangliosidosis, AB variant, a rare
GM2 gangliosidosis
The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are bette ...
that has symptoms and pathology identical with
Tay–Sachs disease
Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby ...
and
Sandhoff disease
Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, ...
.
GM2A mutations are rarely reported, and the cases that are observed often occur with
consanguineous
Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor).
Many jurisdictions have laws prohibiting people who are related by blood fro ...
parents or in genetically isolated populations.
Because AB variant is so rarely diagnosed, even in infants, it is likely that most mutations of GM2A are fatal in the fetus in
homozygotes and
genetic compounds, and thus are never observed clinically.
See also
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Gangliosidosis
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Sandhoff disease
Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, ...
*
Tay–Sachs disease
Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby ...
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Hexosaminidase
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GM1
GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair ...
References
Further reading
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Cell signaling
Peripheral membrane proteins
Water-soluble transporters
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