GBA3

Glucosylceramidase beta 2
Identifiers
Symbol	?
HGNC	4170
OMIM	609471
RefSeq	NM_020944
UniProt	Q9HCG7
Search for Structures Swiss-model Domains InterPro

Glucosylceramidase beta 2 (GBA2) is an enzyme encoded by the GBA2 gene in humans. This enzyme is involved in the metabolism of glycosphingolipids, specifically in the hydrolysis of glucosylceramide to ceramide and glucose.

Function

GBA2 is a non-lysosomal glucosylceramidase that plays a crucial role in the breakdown of glucosylceramide, a type of glycosphingolipid. Unlike its lysosomal counterpart, GBA1, which is associated with Gaucher's disease, GBA2 functions in the cytosol and is involved in the regulation of cellular lipid homeostasis. The enzyme's activity is essential for maintaining the balance of sphingolipids, which are important components of cell membranes and play roles in cell signaling.

Structure

The GBA2 protein is a member of the GH116 family of glycoside hydrolases. It is characterized by its ability to cleave the beta-glucosidic bond in glucosylceramide. The enzyme's structure includes a catalytic domain that is responsible for its hydrolase activity. The precise three-dimensional structure of GBA2 is still under investigation, but it is known to differ significantly from the lysosomal GBA1 enzyme.

Clinical Significance

Mutations in the GBA2 gene have been associated with a range of neurological disorders. Notably, defects in GBA2 can lead to hereditary spastic paraplegia (HSP), a group of inherited disorders characterized by progressive weakness and spasticity of the lower limbs. Additionally, GBA2 mutations have been implicated in cerebellar ataxia, a condition that affects coordination and balance.

Research has also suggested a potential link between GBA2 activity and Parkinson's disease, although the exact relationship remains to be fully elucidated. The enzyme's role in lipid metabolism and its impact on neuronal function make it a subject of interest in neurodegenerative disease research.

Research Directions

Current research on GBA2 focuses on understanding its precise role in cellular lipid metabolism and its implications in neurological diseases. Studies are exploring the potential of targeting GBA2 for therapeutic interventions in disorders associated with sphingolipid imbalances. Additionally, the development of specific inhibitors or activators of GBA2 could provide new avenues for treating related conditions.

Also see

• Glycosphingolipid metabolism
• GBA1
• Hereditary spastic paraplegia
• Cerebellar ataxia
• Parkinson's disease