InterPro domain: IPR024462

This entry represents the N-terminal domain found in the CAZyme GH116 family members, which presently includes enzymes with beta-glucosidase ( 3.2.1.21 ), beta-xylosidase ( 3.2.1.37 ) , and glucocerebrosidase ( 3.2.1.45 ) activity [ 1 , 2 ]. The N-terminal is thought to be the luminal domain while the C-terminal is the cytosolic domain.

Proteins containing this domain include animal non-lysosomal glucosylceramidase GBA2, which catalyse the conversion of glucosylceramide to free glucose and ceramide [ 3 ]. GBA2 is involved in sphingomyelin generation and prevention of glycolipid accumulation and may also catalyse the hydrolysis of bile acid 3-O-glucosides, however, the relevance of such activity is unclear in vivo [ 4 ]. Mutations in the human protein cause motor-neurone defects in hereditary spastic paraplegia [ 5 ].

1. Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity. Am. J. Hum. Genet. 92, 245-51
2. A new archaeal beta-glycosidase from Sulfolobus solfataricus: seeding a novel retaining beta-glycan-specific glycoside hydrolase family along with the human non-lysosomal glucosylceramidase GBA2. J. Biol. Chem. 285, 20691-703
3. Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2. J. Biol. Chem. 282, 1305-12
4. Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility. J. Clin. Invest. 116, 2985-94