GM2A
Encyclopedia
GM2 ganglioside activator also known as GM2A is a protein
which in humans is encoded by the GM2A gene
.
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, and also T-cell activation through lipid presentation. This protein binds molecules of ganglioside
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 and lipid metabolism
in the SMART database.
http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=ML&BLAST=DUMMY.
.
, a rare GM2 gangliosidosis
that has symptoms and pathology identical with Tay-Sachs disease
and Sandhoff disease
.
GM2A mutations are rarely reported, and the cases that are observed often occur with consanguineous 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.
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...
which in humans is encoded by the GM2A 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...
.
Function
The protein encoded by this gene is a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomalLysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
enzyme β-hexosaminidase A
HEXA
Hexosaminidase A , also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene.Hexosaminidase A and the cofactor GM2 activator protein catalyze the degradation of the GM2 gangliosides and other molecules containing terminal N-acetyl hexosamines...
. β-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2
GM2 (ganglioside)
GM2 is a type of ganglioside. It is associated with GM2 gangliosidoses such as Tay-Sachs disease....
, and other molecules containing terminal N-acetyl hexosamines.
GM2A is a lipid transfer protein that stimulates the enzymatic processing of gangliosides, and also T-cell activation through lipid presentation. This protein binds molecules of ganglioside
Ganglioside
Ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. The 60+ known gangliosides differ mainly in the position and number of NANA residues.It is a component of the cell plasma membrane that modulates cell signal transduction events...
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
ML domain
The MD-2-related lipid-recognition domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like beta-sandwich fold similar to that of immunoglobulin E-set domains...
family of proteins involved in innate immunity and lipid metabolism
Lipid metabolism
Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.The types of lipids involved include:* Bile salts* Cholesterols* Eicosanoids* Glycolipids* Ketone bodies* Fatty acids - see also fatty acid metabolism...
in the SMART database.
http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=ML&BLAST=DUMMY.
Regulation
In melanocytic cells GM2A gene expression may be regulated by MITFMicrophthalmia-associated transcription factor
Microphthalmia-associated transcription factor is a basic helix-loop-helix leucine zipper transcription factor involved in melanocyte and osteoclast development.-Clinical significance:...
.
Clinical significance
Mutations in this gene, inherited in an autosomal recessive pattern, result in GM2-gangliosidosis, AB variantGM2-gangliosidosis, AB variant
GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay-Sachs disease...
, a rare GM2 gangliosidosis
GM2 gangliosidoses
The GM2 gangliosidoses are a group of 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 better known by their individual names.Beta-hexosaminidase is a...
that has symptoms and pathology identical with Tay-Sachs disease
Tay-Sachs disease
Tay–Sachs disease is an autosomal recessive genetic disorder...
and Sandhoff disease
Sandhoff disease
Sandhoff disease, also known as Sandhoff-Jatzkewitz disease, variant 0 of GM2-Gangliosidosis or Hexosaminidase A and B deficiency, is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B...
.
GM2A mutations are rarely reported, and the cases that are observed often occur with consanguineous 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
- GangliosidosisGangliosidosisGangliosidosis is a lipid storage disorder caused by the accumulation of lipids known as gangliosides. There are two distinct genetic causes of the disease. Both are autosomal recessive and affect males and females equally.-See also:...
- Sandhoff diseaseSandhoff diseaseSandhoff disease, also known as Sandhoff-Jatzkewitz disease, variant 0 of GM2-Gangliosidosis or Hexosaminidase A and B deficiency, is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B...
- Tay-Sachs diseaseTay-Sachs diseaseTay–Sachs disease is an autosomal recessive genetic disorder...
- HexosaminidaseHexosaminidaseHexosaminidase is an enzyme involved in the hydrolysis of terminal N-acetyl-D-hexosamine residues in N-acetyl-β-D-hexosaminides.- Lysosomal A, B, and S isozymes :Functional lysosomal β-hexosaminidase enzymes are dimeric in structure...
- GM1GM1GM1 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 mechanisms, and the release of neurotrophins in the brain...