ASAH1

ASAH1
Identifiers
Aliases	ASAH1, AC, ACDase, ASAH, PHP, PHP32, SMAPME, N-acylsphingosine amidohydrolase (acid ceramidase) 1, N-acylsphingosine amidohydrolase 1
External IDs	OMIM: 613468; MGI: 1277124; HomoloGene: 10504; GeneCards: ASAH1; OMA:ASAH1 - orthologs
Gene location (Human) Chr. Chromosome 8 (human) Band 8p22 Start 18,055,992 bp End 18,084,998 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8|8 A4 Start 41,793,234 bp End 41,827,810 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle visceral pleura pancreatic ductal cell retinal pigment epithelium myocardium parietal pleura nasal epithelium monocyte renal medulla left ventricle Top expressed in saccule stroma of bone marrow endothelial cell of lymphatic vessel otic placode iris calvaria ciliary body parotid gland Epithelium of choroid plexus epithelium of stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function N-acylsphingosine amidohydrolase activity catalytic activity hydrolase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ceramidase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides Cellular component lysosome lysosomal lumen extracellular exosome extracellular region extracellular space tertiary granule lumen ficolin-1-rich granule lumen early endosome endoplasmic reticulum nucleus cytoplasm Biological process glycosphingolipid metabolic process ceramide metabolic process lipid metabolism neutrophil degranulation sphingosine biosynthetic process ceramide biosynthetic process ceramide catabolic process keratinocyte differentiation regulation of steroid biosynthetic process regulation of programmed necrotic cell death cellular response to tumor necrosis factor sphingolipid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 427 11886 Ensembl ENSG00000104763 ENSMUSG00000031591 UniProt Q13510 Q9WV54 RefSeq (mRNA) NM_001127505 NM_004315 NM_177924 NM_001363743 NM_019734 RefSeq (protein) NP_001120977 NP_004306 NP_808592 NP_001350672 NP_062708 Location (UCSC) Chr 8: 18.06 – 18.08 Mb Chr 8: 41.79 – 41.83 Mb PubMed search
Wikidata
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The ASAH1 gene encodes in humans the acid ceramidase enzyme.

Function

This gene encodes a heterodimeric protein consisting of a nonglycosylated alpha subunit and a glycosylated beta subunit that is cleaved to the mature enzyme posttranslationally. The encoded protein catalyzes the synthesis and degradation of ceramide into sphingosine and fatty acid. Mutations in this gene have been associated with a lysosomal storage disorder known as Farber disease and, recently, with a rare neurodegenerative condition known as spinal muscular atrophy with progressive myoclonic epilepsy. Two transcript variants encoding distinct isoforms have been identified for this gene. In melanocytic cells ASAH1 gene expression may be regulated by MITF.

As a glioblastoma drug target

ASAH1 expression is upregulated following radiation, suggesting it plays a role in conferring radioresistance to glioblastoma and in the development of recurrent glioblastoma. Inhibiting the activity of ASAH1 with carmofur, a drug that has been approved for clinical treatment of colorectal cancers in several countries, leads to substantial cell deaths and as a result has been proposed as a drug target in the treatment of glioblastoma. It has also been suggested to be a novel drug target against pediatric brain tumors as well.

External links

• Human ASAH1 genome location and ASAH1 gene details page in the UCSC Genome Browser.

Further reading

• Perry DK, Hannun YA (December 1998). "The role of ceramide in cell signaling". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1436 (1–2): 233–43. doi:10.1016/S0005-2760(98)00145-3. PMID 9838138.
• Bernardo K, Hurwitz R, Zenk T, Desnick RJ, Ferlinz K, Schuchman EH, Sandhoff K (May 1995). "Purification, characterization, and biosynthesis of human acid ceramidase". The Journal of Biological Chemistry. 270 (19): 11098–102. doi:10.1074/jbc.270.19.11098. PMID 7744740.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Seelan RS, Qian C, Yokomizo A, Bostwick DG, Smith DI, Liu W (October 2000). "Human acid ceramidase is overexpressed but not mutated in prostate cancer". Genes, Chromosomes & Cancer. 29 (2): 137–46. doi:10.1002/1098-2264(2000)9999:9999<::AID-GCC1018>3.0.CO;2-E. PMID 10959093. S2CID 21766341.
• Strelow A, Bernardo K, Adam-Klages S, Linke T, Sandhoff K, Krönke M, Adam D (September 2000). "Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death". The Journal of Experimental Medicine. 192 (5): 601–12. doi:10.1084/jem.192.5.601. PMC 2193270. PMID 10974027.
• Bär J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K (March 2001). "Molecular analysis of acid ceramidase deficiency in patients with Farber disease". Human Mutation. 17 (3): 199–209. doi:10.1002/humu.5. PMID 11241842. S2CID 39656479.
• Ferlinz K, Kopal G, Bernardo K, Linke T, Bar J, Breiden B, Neumann U, Lang F, Schuchman EH, Sandhoff K (September 2001). "Human acid ceramidase: processing, glycosylation, and lysosomal targeting". The Journal of Biological Chemistry. 276 (38): 35352–60. doi:10.1074/jbc.M103066200. PMID 11451951.
• Muramatsu T, Sakai N, Yanagihara I, Yamada M, Nishigaki T, Kokubu C, Tsukamoto H, Ito M, Inui K (November 2002). "Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease". Journal of Inherited Metabolic Disease. 25 (7): 585–92. doi:10.1023/A:1022047408477. PMID 12638942. S2CID 26208268.
• Zhang H, Li XJ, Martin DB, Aebersold R (June 2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". Nature Biotechnology. 21 (6): 660–6. doi:10.1038/nbt827. PMID 12754519. S2CID 581283.
• Okino N, He X, Gatt S, Sandhoff K, Ito M, Schuchman EH (August 2003). "The reverse activity of human acid ceramidase". The Journal of Biological Chemistry. 278 (32): 29948–53. doi:10.1074/jbc.M303310200. PMID 12764132.
• He X, Okino N, Dhami R, Dagan A, Gatt S, Schulze H, Sandhoff K, Schuchman EH (August 2003). "Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase". The Journal of Biological Chemistry. 278 (35): 32978–86. doi:10.1074/jbc.M301936200. PMID 12815059.
• Hara S, Nakashima S, Kiyono T, Sawada M, Yoshimura S, Iwama T, Banno Y, Shinoda J, Sakai N (August 2004). "p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis". Cell Death and Differentiation. 11 (8): 853–61. doi:10.1038/sj.cdd.4401428. PMID 15088070.
• Lewandrowski U, Moebius J, Walter U, Sickmann A (February 2006). "Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach". Molecular & Cellular Proteomics. 5 (2): 226–33. doi:10.1074/mcp.M500324-MCP200. PMID 16263699.