ID:GLCM_HUMAN DESCRIPTION: RecName: Full=Glucosylceramidase; EC=3.2.1.45; AltName: Full=Acid beta-glucosidase; AltName: Full=Alglucerase; AltName: Full=Beta-glucocerebrosidase; AltName: Full=D-glucosyl-N-acylsphingosine glucohydrolase; AltName: Full=Imiglucerase; Flags: Precursor; CATALYTIC ACTIVITY: D-glucosyl-N-acylsphingosine + H(2)O = D- glucose + N-acylsphingosine. ENZYME REGULATION: Requires saposin-C and anionic phospholipids for activity. SUBUNIT: Interacts with saposin-C. Interacts with SCARB2. INTERACTION: O35114:Scarb2 (xeno); NbExp=1; IntAct=EBI-1564609, EBI-1564519; SUBCELLULAR LOCATION: Lysosome membrane; Peripheral membrane protein; Lumenal side. Note=Interaction with saposin-C promotes membrane association. Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2. DISEASE: Defects in GBA are the cause of Gaucher disease (GD) [MIM:230800]; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, characterized by accumulation of glucosylceramide in the reticulo-endothelial system. Different clinical forms are recognized depending on the presence (neuronopathic forms) or absence of central nervous system involvement, severity and age of onset. DISEASE: Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:230800]; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved. DISEASE: Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:230900]; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age. DISEASE: Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:231000]; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations. DISEASE: Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:231005]; also known as pseudo-Gaucher disease or Gaucher-like disease. DISEASE: Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:608013]. It is a 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. DISEASE: Note=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. DISEASE: Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:168600]. 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. PHARMACEUTICAL: Available under the names Ceredase and Cerezyme (Genzyme). Used to treat Gaucher's disease. SIMILARITY: Belongs to the glycosyl hydrolase 30 family. WEB RESOURCE: Name=Ceredase; Note=Clinical information on Ceredase; URL="http://www.rxlist.com/ceredase-drug.htm"; WEB RESOURCE: Name=Cerezyme; Note=Clinical information on Cerezyme; URL="http://www.rxlist.com/cerezyme-drug.htm"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GBA";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P04062
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006629 lipid metabolic process GO:0006665 sphingolipid metabolic process GO:0006680 glucosylceramide catabolic process GO:0008152 metabolic process GO:0009267 cellular response to starvation GO:0009268 response to pH GO:0016241 regulation of macroautophagy GO:0023021 termination of signal transduction GO:0032268 regulation of cellular protein metabolic process GO:0032269 negative regulation of cellular protein metabolic process GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032463 negative regulation of protein homooligomerization GO:0032715 negative regulation of interleukin-6 production GO:0033561 regulation of water loss via skin GO:0033574 response to testosterone GO:0035307 positive regulation of protein dephosphorylation GO:0043243 positive regulation of protein complex disassembly GO:0043407 negative regulation of MAP kinase activity GO:0043589 skin morphogenesis GO:0043627 response to estrogen GO:0046512 sphingosine biosynthetic process GO:0046513 ceramide biosynthetic process GO:0050728 negative regulation of inflammatory response GO:0051246 regulation of protein metabolic process GO:0051247 positive regulation of protein metabolic process GO:0071356 cellular response to tumor necrosis factor GO:0071548 response to dexamethasone GO:0097066 response to thyroid hormone GO:1901215 negative regulation of neuron death GO:1901805 beta-glucoside catabolic process GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process GO:1903061 positive regulation of protein lipidation GO:1904457 positive regulation of neuronal action potential GO:1904925 positive regulation of mitophagy in response to mitochondrial depolarization GO:1905037 autophagosome organization GO:1905165 regulation of lysosomal protein catabolic process GO:0007005 mitochondrion organization GO:0031175 neuron projection development GO:0036473 cell death in response to oxidative stress
KJ690773 - Homo sapiens clone 4D glucosylceramidase-like protein mRNA, complete cds. KJ690772 - Homo sapiens clone 11G glucosylceramidase-like protein mRNA, complete cds. BC003356 - Homo sapiens glucosidase, beta; acid (includes glucosylceramidase), mRNA (cDNA clone MGC:5191 IMAGE:2899915), complete cds. M19285 - Human glucocerebrosidase mRNA, complete cds. BX648487 - Homo sapiens mRNA; cDNA DKFZp686D0678 (from clone DKFZp686D0678). M16328 - Human glucocerebrosidase mRNA, complete cds. D13286 - Homo sapiens mRNA for glucocerebrosidase, complete cds. AH001468 - Homo sapiens glucocerebrosidase mRNA mRNA, partial sequence. JD084738 - Sequence 65762 from Patent EP1572962. JD496617 - Sequence 477641 from Patent EP1572962. AK298900 - Homo sapiens cDNA FLJ50618 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). JD064453 - Sequence 45477 from Patent EP1572962. JD555386 - Sequence 536410 from Patent EP1572962. JD073335 - Sequence 54359 from Patent EP1572962. JD479520 - Sequence 460544 from Patent EP1572962. JD308813 - Sequence 289837 from Patent EP1572962. JD182795 - Sequence 163819 from Patent EP1572962. JD396385 - Sequence 377409 from Patent EP1572962. AK291911 - Homo sapiens cDNA FLJ77760 complete cds, highly similar to Homo sapiens glucosidase, beta; acid (includes glucosylceramidase), mRNA. AK301374 - Homo sapiens cDNA FLJ50709 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). JD553328 - Sequence 534352 from Patent EP1572962. K02920 - Homo sapiens lysosomal glucocerebrosidase precursor mRNA, complete cds. AK302000 - Homo sapiens cDNA FLJ56170 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). AK300829 - Homo sapiens cDNA FLJ50695 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). JD039095 - Sequence 20119 from Patent EP1572962. AK300876 - Homo sapiens cDNA FLJ56157 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). JD340180 - Sequence 321204 from Patent EP1572962. JD044468 - Sequence 25492 from Patent EP1572962. JD511909 - Sequence 492933 from Patent EP1572962. AK300186 - Homo sapiens cDNA FLJ51780 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). KJ690771 - Homo sapiens clone 2G glucosylceramidase (GBA) mRNA, complete cds. AK312502 - Homo sapiens cDNA, FLJ92865, Homo sapiens glucosidase, beta; acid (includes glucosylceramidase)(GBA), mRNA. KJ891223 - Synthetic construct Homo sapiens clone ccsbBroadEn_00617 GBA gene, encodes complete protein. KR709321 - Synthetic construct Homo sapiens clone CCSBHm_00000006 GBA (GBA) mRNA, encodes complete protein. KR709322 - Synthetic construct Homo sapiens clone CCSBHm_00000073 GBA (GBA) mRNA, encodes complete protein. KR709323 - Synthetic construct Homo sapiens clone CCSBHm_00000113 GBA (GBA) mRNA, encodes complete protein. KR709324 - Synthetic construct Homo sapiens clone CCSBHm_00000231 GBA (GBA) mRNA, encodes complete protein. AB527624 - Synthetic construct DNA, clone: pF1KB3573, Homo sapiens GBA gene for glucosidase, beta, without stop codon, in Flexi system. AK301879 - Homo sapiens cDNA FLJ50423 complete cds, highly similar to Glucosylceramidase precursor (EC 3.2.1.45). DL491709 - Novel nucleic acids. DL490290 - Novel nucleic acids. AK311242 - Homo sapiens cDNA, FLJ18284. JD439832 - Sequence 420856 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P04062 (Reactome details) participates in the following event(s):
R-HSA-390470 Association of CCT/TriC with other substrates during biosynthesis (unknown chaperone) R-HSA-1605591 Glucosylceramidase cleaves the glucosidic bond of glucocerebroside to form ceramide R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis R-HSA-1660662 Glycosphingolipid metabolism R-HSA-390466 Chaperonin-mediated protein folding R-HSA-428157 Sphingolipid metabolism R-HSA-391251 Protein folding R-HSA-556833 Metabolism of lipids R-HSA-392499 Metabolism of proteins R-HSA-1430728 Metabolism
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
