ASAH1
Identifiers
AliasesASAH1, AC, ACDase, ASAH, PHP, PHP32, SMAPME, N-acylsphingosine amidohydrolase (acid ceramidase) 1, N-acylsphingosine amidohydrolase 1
External IDsOMIM: 613468 MGI: 1277124 HomoloGene: 10504 GeneCards: ASAH1
Orthologs
SpeciesHumanMouse
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 MbChr 8: 41.79 – 41.83 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The ASAH1 gene encodes in humans the acid ceramidase enzyme.[5][6][7]

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.[8] Two transcript variants encoding distinct isoforms have been identified for this gene.[7] In melanocytic cells ASAH1 gene expression may be regulated by MITF.[9]

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.[10] 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.[11] It has also been suggested to be a novel drug target against pediatric brain tumors as well.[12]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000104763 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031591 - 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.
  5. Koch J, Gärtner S, Li CM, Quintern LE, Bernardo K, Levran O, Schnabel D, Desnick RJ, Schuchman EH, Sandhoff K (December 1996). "Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification Of the first molecular lesion causing Farber disease". The Journal of Biological Chemistry. 271 (51): 33110–5. doi:10.1074/jbc.271.51.33110. PMID 8955159.
  6. Li CM, Park JH, He X, Levy B, Chen F, Arai K, Adler DA, Disteche CM, Koch J, Sandhoff K, Schuchman EH (December 1999). "The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression". Genomics. 62 (2): 223–31. doi:10.1006/geno.1999.5940. PMID 10610716.
  7. 1 2 "Entrez Gene: ASAH1 N-acylsphingosine amidohydrolase (acid ceramidase) 1".
  8. Zhou J, Tawk M, Tiziano FD, Veillet J, Bayes M, Nolent F, Garcia V, Servidei S, Bertini E, Castro-Giner F, Renda Y, Carpentier S, Andrieu-Abadie N, Gut I, Levade T, Topaloglu H, Melki J (July 2012). "Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1". American Journal of Human Genetics. 91 (1): 5–14. doi:10.1016/j.ajhg.2012.05.001. PMC 3397266. PMID 22703880.
  9. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
  10. Doan NB, Nguyen HS, Al-Gizawiy MM, Mueller WM, Sabbadini RA, Rand SD, Connelly JM, Chitambar CR, Schmainda KM, Mirza SP (October 2017). "Acid ceramidase confers radioresistance to glioblastoma cells". Oncology Reports. 38 (4): 1932–40. doi:10.3892/or.2017.5855. PMC 5652937. PMID 28765947.
  11. Doan NB, Alhajala H, Al-Gizawiy MM, Mueller WM, Rand SD, Connelly JM, Cochran EJ, Chitambar CR, Clark P, Kuo J, Schmainda KM, Mirza SP (December 2017). "Acid ceramidase and its inhibitors: a de novo drug target and a new class of drugs for killing glioblastoma cancer stem cells with high efficiency". Oncotarget. 8 (68): 112662–74. doi:10.18632/oncotarget.22637. PMC 5762539. PMID 29348854.
  12. Doan NB, Nguyen HS, Montoure A, Al-Gizawiy MM, Mueller WM, Kurpad S, Rand SD, Connelly JM, Chitambar CR, Schmainda KM, Mirza SP (April 2017). "Acid ceramidase is a novel drug target for pediatric brain tumors". Oncotarget. 8 (15): 24753–61. doi:10.18632/oncotarget.15800. PMC 5421885. PMID 28445970.

Further reading


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