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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:15916907, PubMed:24211208, PubMed:32144204, PubMed:9201993). 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 (Probable) (PubMed:26724485). 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).

Involvement in disease

Gaucher disease

GD

An autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD is a multisystem disease historically divided into three main subtypes on the basis of the presence of neurologic involvement, age at onset and progression rate: type 1 is the non-neuropathic form, type 2 is the acute neuropathic form with early onset and rapid neurologic deterioration, type 3 is the chronic neuropathic form with slow progression of neurologic features. GD shows a marked phenotypic diversity ranging from adult asymptomatic forms, at the mild end, to perinatal lethal forms at the severe end of the disease spectrum. Formal diagnosis of Gaucher disease is based on the measurement of glucocerebrosidase levels in circulating leukocytes and molecular genetic analysis.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 1

GD1

A form of Gaucher disease, an autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 2

GD2

The most severe form of Gaucher disease, an autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD2 is an acute neuronopathic form that manifests soon after birth, with death generally occurring before patients reach two years of age. Clinical features include hepatosplenomegaly, developmental regression, growth arrest, and rapidly progressing neurologic deterioration.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 3

GD3

A form of Gaucher disease, an autosomal recessive lysosomal storage disease due to deficient activity of lysosomal beta-glucocerebrosidase, and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. GD3 is a subacute neuronopathic form characterized by later onset and slower progression compared to Gaucher disease 2.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 3C

GD3C

A variant of subacute neuronopathic Gaucher disease 3 associated with cardiovascular calcifications.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease perinatal lethal

GDPL

Distinct form of Gaucher disease type 2, characterized by fetal onset. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurologic involvement begins in the first week and leads to death within 3 months. Hepatosplenomegaly is a major sign, and is associated with ichthyosis, arthrogryposis, and facial dysmorphism.

None

The disease is caused by variants affecting the gene represented in this entry. Perinatal lethal Gaucher disease is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.

Parkinson disease

PARK

A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.

None

Disease susceptibility may be associated with variants affecting the gene represented in this entry.

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 (PubMed:10781797). Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2 (PubMed:18022370).

Alternative names

GBA, GC, GLUC, GBA1, Lysosomal acid glucosylceramidase, Lysosomal acid GCase, 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, Beta-GC, SGTase

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

59716Da

We found 13 products in 3 categories

Primary Antibodies

Assay Kits

Target

Reactive species

Detection method

Proteins & Peptides

Target

Species of origin