GM2 ganglioside activator also known as GM2A is a protein which in humans is encoded by the GM2A gene. [5] [6]
GM2 ganglioside activator also known as GM2A is a protein which in humans is encoded by the GM2A gene. [5] [6]
The protein encoded by this gene is a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal 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. .
In melanocytic cells GM2A gene expression may be regulated by MITF. [7]
Mutations in this gene, inherited in an autosomal recessive pattern, result in GM2-gangliosidosis, AB variant, a rare GM2 gangliosidosis that has symptoms and pathology identical with Tay–Sachs disease and Sandhoff disease. [8]
GM2A mutations are rarely reported, and the cases that are observed often occur with consanguineous parents or in genetically isolated populations. [9]
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.
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 losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of four. Less commonly, the disease may occur in later childhood or adulthood. These forms tend to be less severe, but the juvenile form typically results in death by age 15.
Keratin 9 is a protein that in humans is encoded by the KRT9 gene.
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, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
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. The three diseases are classified together as the GM2 gangliosidoses, because each disease represents a distinct molecular point of failure in the activation of the same enzyme, beta-hexosaminidase. AB variant is caused by a failure in the gene that makes an enzyme cofactor for beta-hexosaminidase, called the GM2 activator.
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 better known by their individual names: Tay–Sachs disease, AB variant, and Sandhoff disease.
Hexosaminidase is an enzyme involved in the hydrolysis of terminal N-acetyl-D-hexosamine residues in N-acetyl-β-D-hexosaminides.
Beta-hexosaminidase subunit beta is an enzyme that in humans is encoded by the HEXB gene.
Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.
Prosaposin, also known as PSAP, is a protein which in humans is encoded by the PSAP gene.
Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the GLB1 gene.
Hexosaminidase A , also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene, located on the 15th chromosome.
Lysophosphatidic acid receptor 2 also known as LPA2 is a protein that in humans is encoded by the LPAR2 gene. LPA2 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).
The ASAH1 gene encodes in humans the acid ceramidase enzyme.
Ganglioside-induced differentiation-associated protein 1 is a protein that in humans is encoded by the GDAP1 gene.
CCAAT/enhancer-binding protein gamma is a protein that in humans is encoded by the CEBPG gene.
Lactosylceramide alpha-2,3-sialyltransferase is an enzyme that in humans is encoded by the ST3GAL5 gene.
Ubiquitin-conjugating enzyme E2 H is a protein that in humans is encoded by the UBE2H gene.
Sialidase-2 is an enzyme that in humans is encoded by the NEU2 gene.
Homeobox protein SIX2 is a protein that in humans is encoded by the SIX2 gene.
In molecular biology, the CHB HEX N-terminal domain represents the N-terminal domain in chitobiases and beta-hexosaminidases. Chitobiases degrade chitin, which forms the exoskeleton in insects and crustaceans, and which is one of the most abundant polysaccharides on earth. Beta-hexosaminidases are composed of either a HexA/HexB heterodimer or a HexB homodimer, and can hydrolyse diverse substrates, including GM(2)-gangliosides; mutations in this enzyme are associated with Tay–Sachs disease. HexB is structurally similar to chitobiase, consisting of a beta sandwich structure; this structure is similar to that found in the cellulose-binding domain of cellulase from Cellulomonas fimi. This domain may function as a carbohydrate binding module.
PDB gallery | |
|---|---|
|
 | This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it. |
