Galactosylceramidase

Galactosylceramidase
Identifiers
EC no.	3.2.1.46
CAS no.	9027-89-8
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Galactosylceramidase (or galactocerebrosidase), EC 3.2.1.46, is an enzyme that removes galactose from ceramide derivatives (galactosylceramides) by catalysing the hydrolysis of galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. ^[1]

It is a lysosomal protein, encoded in humans by the GALC gene. ^{[1] [2]} Mutations in this gene have been associated with Krabbe disease, also known as galactosylceramide lipidosis. ^[1]

References

1. "Entrez Gene: galactosylceramidase".
2. Lee WC, Tsoi YK, Troendle FJ, et al. (August 2007). "Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy" . FASEB J. 21 (10): 2520–2527. doi: 10.1096/fj.06-6169com . PMID   17403939. S2CID   19511563.

GALC
Identifiers
Aliases	GALC , entrez:2581, galactosylceramidase
External IDs	OMIM: 606890; MGI: 95636; HomoloGene: 124; GeneCards: GALC; OMA:GALC - orthologs
Gene location (Human) Chr. Chromosome 14 (human) [1] Band 14q31.3 Start 87,837,820 bp [1] End 87,993,665 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12 E|12 49.83 cM Start 98,168,553 bp [2] End 98,225,718 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bronchial epithelial cell jejunal mucosa glomerulus metanephric glomerulus germinal epithelium optic nerve retinal pigment epithelium duodenum trigeminal ganglion inferior ganglion of vagus nerve Top expressed in stroma of bone marrow human kidney epithelium of lens submandibular gland right kidney granulocyte iris seminiferous tubule gastrula ciliary body More reference expression data BioGPS n/a
Gene ontology Molecular function hydrolase activity hydrolase activity, acting on glycosyl bonds galactosylceramidase activity catalytic activity Cellular component lysosome lysosomal lumen Biological process lipid catabolic process metabolism galactosylceramide catabolic process glycosphingolipid metabolic process lipid metabolism sphingolipid metabolic process myelination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2581 14420 Ensembl ENSG00000054983 ENSMUSG00000021003 UniProt P54803 P54818 RefSeq (mRNA) NM_000153 NM_001037525 NM_001201401 NM_001201402 NM_008079 RefSeq (protein) NP_000144 NP_001188330 NP_001188331 NP_032105 Location (UCSC) Chr 14: 87.84 – 87.99 Mb Chr 12: 98.17 – 98.23 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Further reading

• Lee WC, Kang D, Causevic E, et al. (2010). "Molecular characterization of mutations that cause globoid cell leukodystrophy and pharmacological rescue using small molecule chemical chaperones". J. Neurosci. 30 (16): 5489–5497. doi:10.1523/JNEUROSCI.6383-09.2010. PMC   3278277 . PMID   20410102.
• Wenger DA, Rafi MA, Luzi P (1997). "Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications". Hum. Mutat. 10 (4): 268–279. doi: 10.1002/(SICI)1098-1004(1997)10:4<268::AID-HUMU2>3.0.CO;2-D . PMID   9338580. S2CID   36148722.
• De Gasperi R, Gama Sosa MA, Sartorato EL, et al. (1996). "Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy". Am. J. Hum. Genet. 59 (6): 1233–1242. PMC   1914878 . PMID   8940268.
• Tappino B, Biancheri R, Mort M, et al. (2010). "Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease". Hum. Mutat. 31 (12): E1894–1914. doi:10.1002/humu.21367. PMC   3052420 . PMID   20886637.
• Formichi P, Radi E, Battisti C, et al. (2007). "Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients". J. Cell. Physiol. 212 (3): 737–743. doi:10.1002/jcp.21070. PMID   17458901. S2CID   39182882.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• Franke A, McGovern DP, Barrett JC, et al. (2010). "Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci". Nat. Genet. 42 (12): 1118–1125. doi:10.1038/ng.717. PMC   3299551 . PMID   21102463.
• Wenger DA, Rafi MA, Luzi P, et al. (2000). "Krabbe disease: genetic aspects and progress toward therapy". Mol. Genet. Metab. 70 (1): 1–9. doi:10.1006/mgme.2000.2990. PMID   10833326.
• Lissens W, Arena A, Seneca S, et al. (2007). "A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region". Hum. Mutat. 28 (7): 742. doi: 10.1002/humu.9500 . PMID   17579360. S2CID   1705020.
• Beier UH, Görögh T (2005). "Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells". Int. J. Cancer. 115 (1): 6–10. doi:10.1002/ijc.20851. PMID   15657896. S2CID   1013550.
• Xu C, Sakai N, Taniike M, et al. (2006). "Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation". J. Hum. Genet. 51 (6): 548–554. doi: 10.1007/s10038-006-0396-3 . PMID   16607461.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• De Gasperi R, Gama Sosa MA, Sartorato E, et al. (1999). "Molecular basis of late-life globoid cell leukodystrophy". Hum. Mutat. 14 (3): 256–262. doi: 10.1002/(SICI)1098-1004(1999)14:3<256::AID-HUMU9>3.0.CO;2-6 . PMID   10477434. S2CID   27655.
• Furuya H, Kukita Y, Nagano S, et al. (1997). "Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients". Hum. Genet. 100 (3–4): 450–456. doi:10.1007/s004390050532. PMID   9272171. S2CID   22928816.
• Fu L, Inui K, Nishigaki T, et al. (1999). "Molecular heterogeneity of Krabbe disease". J. Inherit. Metab. Dis. 22 (2): 155–162. doi:10.1023/A:1005449919660. PMID   10234611. S2CID   24368901.
• Sakai N, Fukushima H, Inui K, et al. (1998). "Human galactocerebrosidase gene: promoter analysis of the 5'-flanking region and structural organization". Biochim. Biophys. Acta. 1395 (1): 62–67. doi:10.1016/S0167-4781(97)00140-1. PMID   9434153.
• Harzer K, Knoblich R, Rolfs A, et al. (2002). "Residual galactosylsphingosine (psychosine) beta-galactosidase activities and associated GALC mutations in late and very late onset Krabbe disease". Clin. Chim. Acta. 317 (1–2): 77–84. doi:10.1016/S0009-8981(01)00791-4. PMID   11814461.
• Flachsbart F, Franke A, Kleindorp R, et al. (2010). "Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study". Mutat. Res. 694 (1–2): 13–19. Bibcode:2010MRFMM.694...13F. doi:10.1016/j.mrfmmm.2010.08.006. PMID   20800603.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Hendrickson SL, Lautenberger JA, Chinn LW, et al. (2010). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS ONE. 5 (9) e12862. Bibcode:2010PLoSO...512862H. doi: 10.1371/journal.pone.0012862 . PMC   2943476 . PMID   20877624.

External links

• GeneReviews/NCBI/NIH/UW entry on Krabbe disease
• OMIM entries on Krabbe disease
• Galactosylceramidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• PDBe-KB provides an overview of all the structure information available in the PDB for Mlouse Galactocerebrosidase

1. GRCh38: Ensembl release 89: ENSG00000054983 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021003 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.