Gba1
Function
Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose (PubMed:24211208). Plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation (By similarity). Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol (PubMed:24211208). GlcCer containing mono-unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose donors for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4-enine) (By similarity). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide (By similarity). Can also hydrolyze cholesteryl 3-beta-D-glucoside producing glucose and cholesterol (By similarity). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the transfer of galactose between GalCers and cholesterol in vitro, but with lower activity than with GlcCers (By similarity). Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate for hydrolysis, however it is a good xylose donor for transxylosylation activity to form cholesteryl 3-beta-D-xyloside (By similarity).
Pathway
Steroid metabolism; cholesterol metabolism.
Sphingolipid metabolism.
Sequence Similarities
Belongs to the glycosyl hydrolase 30 family.
Cellular localization
- Lysosome membrane
- Peripheral membrane protein
- Lumenal side
- Interaction with saposin-C promotes membrane [?]association. Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2.
Alternative names
Gba, Gba1, Lysosomal acid glucosylceramidase, Lysosomal acid GCase, Acid beta-glucosidase, Beta-glucocerebrosidase, Cholesterol glucosyltransferase, Cholesteryl-beta-glucosidase, D-glucosyl-N-acylsphingosine glucohydrolase, Lysosomal cholesterol glycosyltransferase, Lysosomal galactosylceramidase, Lysosomal glycosylceramidase, SGTase