General Information of the Protein
Protein ID
PT01122
Protein Name
Lysosomal acid glucosylceramidase
Secondarily
Protein Name
Acid beta-glucosidase
Alglucerase
Beta-glucocerebrosidase
Beta-glucosylceramidase 1
Cholesterol glucosyltransferase
Cholesteryl-beta-glucosidase
D-glucosyl-N-acylsphingosine glucohydrolase
Glucosylceramidase beta 1
Imiglucerase
Lysosomal cholesterol glycosyltransferase
Lysosomal galactosylceramidase
Lysosomal glycosylceramidase
Gene Name
GBA1
Secondarily
Gene Name
GBA
GC
GLUC
Sequence
MEFSSPSREECPKPLSRVSIMAGSLTGLLLLQAVSWASGARPCIPKSFGYSSVVCVCNATYCDSFDPPTFPALGTFSRYESTRSGRRMELSMGPIQANHTGTGLLLTLQPEQKFQKVKGFGGAMTDAAALNILALSPPAQNLLLKSYFSEEGIGYNIIRVPMASCDFSIRTYTYADTPDDFQLHNFSLPEEDTKLKIPLIHRALQLAQRPVSLLASPWTSPTWLKTNGAVNGKGSLKGQPGDIYHQTWARYFVKFLDAYAEHKLQFWAVTAENEPSAGLLSGYPFQCLGFTPEHQRDFIARDLGPTLANSTHHNVRLLMLDDQRLLLPHWAKVVLTDPEAAKYVHGIAVHWYLDFLAPAKATLGETHRLFPNTMLFASEACVGSKFWEQSVRLGSWDRGMQYSHSIITNLLYHVVGWTDWNLALNPEGGPNWVRNFVDSPIIVDITKDTFYKQPMFYHLGHFSKFIPEGSQRVGLVASQKNDLDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFLETISPGYSIHTYLWRRQ
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
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:9201993, PubMed:24211208, PubMed:15916907, PubMed:32144204). 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 (PubMed:19279011). Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol (PubMed:24211208, PubMed:26724485, PubMed:32144204). 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) (PubMed:24211208). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide (PubMed:26724485) (Probable). Can also hydrolyze cholesteryl 3-beta-D-glucoside producing glucose and cholesterol (PubMed:24211208, PubMed:26724485). 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 (PubMed:32144204). 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 (PubMed:33361282).
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Uniprot ID
Primary ID:
P04062

Secondarily ID:
A8K796
B7Z5G2
B7Z6S1
J3KQG4
J3KQK9
Q16545
Q4VX22
Q6I9R6
Q9UMJ8
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Ensembl ID
ENSG00000177628
HGNC ID
HGNC:4177
Subcellular Location
Lysosome membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000004 , SH-SY5Y
Compound ID Compound Name Compound Formula
CP0166849
(2R,3R,4R,5S)-1-(5-hexoxypentyl)-2-(hydroxymethyl)piperidine-3,4,5-triol
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C17H35NO5
 1
1
IC50 = 5400 nM
   TI
   LI
   LO
   TS
CP0038675
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol
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C15H31NO4
 1
1
IC50 = 5600 nM
   TI
   LI
   LO
   TS
CP0181793
(2S,3S,4S,5R)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol
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C10H21NO4
 1
1
IC50 = 62000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0038675
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol
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C15H31NO4
 11
1 IC50 = 103 nM
2 IC50 = 300 nM
3 IC50 = 532 nM
4 IC50 = 660 nM
5 IC50 = 790 nM
6 IC50 = 1030 nM
7 IC50 = 1500 nM
8 IC50 = 5584 nM
9 Ki = 300 nM
10 Ki = 620 nM
11 Ki = 1300 nM
Clinical Information about the Protein
Target 1 ( Glucosylceramidase (GBA) )
Target Type Successful Target
Disease 1 Target-related Disease  1
1 Gaucher disease [ICD-11: 5C56.0Y]
Discontinued Drug(s) 1 Discontinued Drug  1
1 Afegostat Discontinued in Phase 2
Gaucher disease
Preclinical Drug(s) 1 Preclinical Drug  1
1 N-Octyl-beta-valienamine Preclinical
Gaucher disease
Target 2 ( Lysosomal acid glucosylceramidase (GBA1) )
Target Type Clinical trial Target