Aliases for ASAH1 Gene
External Ids for ASAH1 Gene
Previous HGNC Symbols for ASAH1 Gene
Previous GeneCards Identifiers for ASAH1 Gene
This gene encodes a member of the acid ceramidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. Processing of this preproprotein generates alpha and beta subunits that heterodimerize to form the mature lysosomal enzyme, which catalyzes the degradation of ceramide into sphingosine and free fatty acid. This enzyme is overexpressed in multiple human cancers and may play a role in cancer progression. Mutations in this gene are associated with the lysosomal storage disorder, Farber lipogranulomatosis, and a neuromuscular disorder, spinal muscular atrophy with progressive myoclonic epilepsy. [provided by RefSeq, Oct 2015]
GeneCards Summary for ASAH1 Gene
ASAH1 (N-Acylsphingosine Amidohydrolase 1) is a Protein Coding gene. Diseases associated with ASAH1 include Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy and Farber Lipogranulomatosis. Among its related pathways are Sphingolipid metabolism and Lysosome. Gene Ontology (GO) annotations related to this gene include N-acylsphingosine amidohydrolase activity. An important paralog of this gene is NAAA.
UniProtKB/Swiss-Prot Summary for ASAH1 Gene
Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:10610716, PubMed:7744740, PubMed:15655246, PubMed:11451951). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:10610716). Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (PubMed:7744740, PubMed:15655246). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:12764132, PubMed:12815059). For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used (PubMed:12764132). Has also an N-acylethanolamine hydrolase activity (PubMed:15655246). By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes (PubMed:17713573). Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis (By similarity). By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis (PubMed:22261821).
[Isoform 2]: May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity.
Ceramidases (EC 220.127.116.11) are a group of enzymes which catalyze the hydrolysis of ceramides to produce sphingosine, which subsequently undergoes phosphorylation to generate sphingosine-1-phosphate (S1P).