Glucocerebrosidase

Glucosidase, beta, acid
250px Acid β-glucosidase, drawn from PDB: 1OGS​ Proteopedia Acid-beta-glucosidase
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1OGS, 1Y7V, 2F61, 2J25, 2NSX, 2NT0, 2NT1, 2V3D, 2V3E, 2V3F, 2VT0, 2WCG, 2WKL, 2XWD, 2XWE, 3GXD, 3GXF, 3GXI, 3GXM, 3KE0, 3KEH, 3RIK, 3RIL
Identifiers
Symbols	GBA ; GBA1; GCB; GLUC
External IDs	OMIM: 606463 MGI: 95665 HomoloGene: 68040 ChEMBL: 2179 GeneCards: GBA Gene
EC number	3.2.1.45
Gene ontology Molecular function • glucosylceramidase activity • receptor binding • protein binding Cellular component • lysosomal membrane • lysosomal lumen • extracellular exosome Biological process • carbohydrate metabolic process • sphingolipid metabolic process • glucosylceramide catabolic process • glycosphingolipid metabolic process • response to pH • termination of signal transduction • negative regulation of interleukin-6 production • regulation of water loss via skin • response to testosterone • positive regulation of protein dephosphorylation • negative regulation of MAP kinase activity • skin morphogenesis • response to estrogen • small molecule metabolic process • sphingosine biosynthetic process • ceramide biosynthetic process • negative regulation of inflammatory response • response to glucocorticoid • cellular response to tumor necrosis factor • response to thyroid hormone • positive regulation of proteolysis involved in cellular protein catabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2629	14466
Ensembl	ENSG00000177628	ENSMUSG00000028048
UniProt	P04062	P17439
RefSeq (mRNA)	NM_000157	NM_001077411
RefSeq (protein)	NP_000148	NP_001070879
Location (UCSC)	Chr 1: 155.23 – 155.24 Mb	Chr 3: 89.2 – 89.21 Mb
PubMed search	[1]	[2]

β-Glucocerebrosidase (also called acid β-glucosidase, D-glucosyl-N-acylsphingosine glucohydrolase, or GCase) is an enzyme with glucosylceramidase activity (EC 3.2.1.45) that is needed to cleave, by hydrolysis, the beta-glucosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism. It is localized in the lysosome and has a molecular weight of 59700 Daltons.

Clinical significance

Mutations in the glucocerebrosidase gene cause Gaucher's disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants encoding the same protein.

Mutations in the glucocerebrosidase gene are also associated with Parkinson's disease.

Drugs

Alglucerase (Ceredase) was a version of glucocerebrosidase that was harvested from human placental tissue and then modified with enzymes. It was approved by the FDA in 1991 and has been withdrawn from the market due to the approval of similar drugs made with recombinant DNA technology instead of being harvested from tissue; drugs made recombinantly, since there is no concern about diseases being transmitted from the tissue used in harvesting, and are less expensive to manufacture.

Recombinant glucocerebrosidases used as drugs include:

• Imiglucerase
• Velaglucerase
• Taliglucerase alfa (Elelyso)

See also

• Closely related enzymes
  • GBA2: acid β-glucosidase (bile acid), also EC 3.2.1.45
  • GBA3: acid β-glucosidase (cytosolic), EC 3.2.1.21

External links

• GeneReviews/NCBI/UW/NIH entry on Gaucher disease
• Glucocerebrosidase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Proteopedia Acid-beta-glucosidase