galactosylceramidase

ガラクトシルセラミダーゼ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/25 11:50:04」(JST)

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Galactosylceramidase
Identifiers
EC number	3.2.1.46
CAS number	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 / EGO
Search PMC articles PubMed articles NCBI proteins

Galactosylceramidase (or galactocerebrosidase) is an enzyme that in humans is encoded by the GALC gene. Galactosylceramidase is an enzyme which removes galactose from ceramide derivatives (galactocerebrosides).

Galactosylceramidase is a lysosomal protein which hydrolyzes the galactose ester bonds of galactocerebroside, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy.

References

Galactosylceramidase
Identifiers
Symbol	GALC
External IDs	OMIM: 606890 MGI: 95636 HomoloGene: 124 GeneCards: GALC Gene
EC number	3.2.1.46
Gene ontology Molecular function • galactosylceramidase activity Cellular component • lysosome • lysosomal lumen • extracellular exosome Biological process • carbohydrate metabolic process • sphingolipid metabolic process • galactosylceramide catabolic process • glycosphingolipid metabolic process • small molecule metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2581	14420
Ensembl	ENSG00000054983	ENSMUSG00000021003
UniProt	P54803	P54818
RefSeq (mRNA)	NM_000153	NM_008079
RefSeq (protein)	NP_000144	NP_032105
Location (UCSC)	Chr 14: 87.84 – 87.99 Mb	Chr 12: 98.2 – 98.26 Mb
PubMed search	[1]	[2]

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): 5489–97. 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): 268–79. doi:10.1002/(SICI)1098-1004(1997)10:4<268::AID-HUMU2>3.0.CO;2-D. PMID 9338580. 
• 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): 1233–42. 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): E1894–914. 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): 737–43. doi:10.1002/jcp.21070. PMID 17458901. 
• 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): 1118–25. 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. 
• 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. 
• 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): 548–54. 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): 2121–7. 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): 256–62. doi:10.1002/(SICI)1098-1004(1999)14:3<256::AID-HUMU9>3.0.CO;2-6. PMID 10477434. 
• 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): 450–6. doi:10.1007/s004390050532. PMID 9272171. 
• Fu L, Inui K, Nishigaki T, et al. (1999). "Molecular heterogeneity of Krabbe disease.". J. Inherit. Metab. Dis. 22 (2): 155–62. doi:10.1023/A:1005449919660. PMID 10234611. 
• 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): 62–7. 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): 13–9. 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): 16899–903. 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. 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 US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. クラッベ病 krabbe disease
• 2. 全身疾患と関連した遺伝性ニューロパチー hereditary neuropathies associated with generalized disorders
• 3. アスパルトアシラーゼ欠乏症（カナバン病） aspartoacylase deficiency canavan disease
• 4. 成人における早期発症の認知症 early onset dementia in adults

English Journal

• Morphological and molecular characterisation of Twitcher mouse spermatogenesis: an update.

• Puggioni E, Governini L, Gori M, Belmonte G, Piomboni P, Costantino-Ceccarini E, Luddi A.
• Reproduction, fertility, and development.Reprod Fertil Dev.2015 Feb 10. doi: 10.1071/RD14279. [Epub ahead of print]
• Spermatogenesis is a complex developmental program in which interactions between different cell types are finely regulated. Mouse models in which any of the sperm maturation steps are perturbed provide major insights into the molecular control of spermatogenesis. The Twitcher mouse is a model of Kra
• PMID 25664578

• GC-EI-MS analysis of fatty acid composition in brain and serum of twitcher mouse.

• Zanfini A1, Dreassi E, Berardi A, Piomboni P, Costantino-Ceccarini E, Luddi A.
• Lipids.Lipids.2014 Nov;49(11):1115-25. doi: 10.1007/s11745-014-3945-0. Epub 2014 Sep 11.
• Globoid cell leukodystrophy or Krabbe disease is an inherited autosomal recessive disorder caused by mutations in the galactosylceramidase gene. The objective of the study was to present information about the fatty acid (FA) composition of the brain and serum of twitcher mice, a mouse model of Krabb
• PMID 25208498

• Ependymoma stem cells are highly sensitive to temozolomide in vitro and in orthotopic models.

• Meco D1, Servidei T1, Lamorte G1, Binda E1, Arena V1, Riccardi R1.
• Neuro-oncology.Neuro Oncol.2014 Aug;16(8):1067-77. doi: 10.1093/neuonc/nou008. Epub 2014 Feb 12.
• BACKGROUND: Ependymoma management remains challenging because of the inherent chemoresistance of this tumor. To determine whether ependymoma stem cells (SCs) might contribute to therapy resistance, we investigated the sensitivity of ependymoma SCs to temozolomide and etoposide.METHODS: The efficacie
• PMID 24526307

Japanese Journal

• Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides

• Zhang Xiaowei,Nakajima Takero,Kamijo Yuji,Li Gang,Hu Rui,Kannagi Reiji,Kyogashima Mamoru,Aoyama Toshifumi,Hara Atsushi
• BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 390(4), 1382-1388, 2009-12-25
• … The treatment also decreased hepatic expression of cerebroside sulfotransferase (CST), a key enzyme in sulfatide metabolism, while it scarcely influenced the expression of the other sulfatide-metabolizing enzymes, including arylsulfatase A, ceramide galactosyltransferase, and galactosylceramidase. …
• NAID 120002647829

• Evolving perspective of the pathogenesis of globoid cell leukodystrophy (Krabbe disease).

• Suzuki Kunihiko
• Proceedings of the Japan Academy, Series B 79B(1), 1-8, 2003
• … However, a more recent experimental mouse model due to genetic defect in saposin A, an in vivo galactosylceramidase activator protein, introduced new elements in our understanding of the disease process. …
• NAID 130000093556

• Ｔｗｉｔｃｈｅｒに学ぶ

• 岡田 伸太郎
• 脳と発達 33(2), 107-113, 2001
• … われわれはヒトKrabbe病のモデルマウスであるtwitcherを用い, 酵素学的, 遺伝子治療的, 病理学的な研究をつづけてきたので紹介する.<BR>欠損酵素はgalactosylceramidaseであり, われわれの手でクローニングされ, 変異領域もつきとめられた.この知見をもとに, twitcherに対して新生児期から遺伝子治療を試み, 生化学的な改善は得られたが, 臨床的には変化なく, 生存期間も延長しなかった.おそらくベクターの感染能が不十分で …
• NAID 130004183453

Related Links

• Galactosylceramidase - Wikipedia, the free encyclopedia

Galactosylceramidase (or galactocerebrosidase) is an enzyme that in humans is encoded by the GALC gene. Galactosylceramidase is an enzyme which removes galactose from ceramide derivatives (galactocerebrosides).

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