ASAH1
entrez
427
canonical
uniprot
Q13510
canonical
ensembl
ENSG00000104763
resolver
ensp
ENSP00000326970
resolver
ensp
ENSP00000371152
resolver
ensp
ENSP00000490071
resolver
ensp
ENSP00000490272
resolver
ensp
ENSP00000490725
resolver
enst
ENST00000636691
resolver
enst
ENST00000637922
resolver
genesymbol
ASAH1
resolver
genesymbol_syn
ASAH
resolver
hgnc
HGNC:735
resolver
uniprot
A0A1B0GUE3
resolver
uniprot
A8K0B6
resolver
uniprot
E9PDS0
resolver
uniprot
Q53H01
resolver
uniprot
Q6W898
resolver
uniprot
Q96AS2
resolver
uniprot_entry
A0A1B0GUE3_HUMAN
resolver
uniprot_entry
A8K0B6_HUMAN
resolver
uniprot_entry
ASAH1_HUMAN
resolver
uniprot_entry
Q53H01_HUMAN
resolver
uniprot_sec
E9PDS0
resolver
uniprot_sec
Q6W898
resolver
uniprot_sec
Q96AS2
resolver
activity_regulation
ACTIVITY REGULATION: Activated by Ca(2+), Mg(2+) and Na(+) cations (PubMed:12764132). Inhibited by Zn(2+) (PubMed:12764132). Phosphatidylserine and phosphatidic acid stimulate while cardiolipin, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and sphingomyelin inhibit the reverse ceramide synthase activity (PubMed:12764132). Phosphatidic acid, phosphatidylinositol and C16-ceramide inhibit the ceramidase/hydrolase activity (PubMed:12764132). {ECO:0000269|PubMed:12764132}.
uniprot
proteins
amino_acid_sequence
MPGRSCVALVLLAAAVSCAVAQHAPPWTEDCRKSTYPPSGPTYRGAVPWYTINLDLPPYKRWHELMLDKAPVLKVIVNSLKNMINTFVPSGKIMQVVDEKLPGLLGNFPGPFEEEMKGIAAVTDIPLGEIISFNIFYELFTICTSIVAEDKKGHLIHGRNMDFGVFLGWNINNDTWVITEQLKPLTVNLDFQRNNKTVFKASSFAGYVGMLTGFKPGLFSLTLNERFSINGGYLGILEWILGKKDVMWIGFLTRTVLENSTSYEEAKNLLTKTKILAPAYFILGGNQSGEGCVITRDRKESLDVYELDAKQGRWYVVQTNYDRWKHPFFLDDRRTPAKMCLNRTSQENISFETMYDVLSTKPVLNKLTVYTTLIDVTKGQFETYLRDCPDPCIGW
uniprot
proteins
disease_involvement
DISEASE: Farber lipogranulomatosis (FRBRL) [MIM:228000]: An autosomal recessive lysosomal storage disorder characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, and marked accumulation of ceramide in lysosomes. Disease severity is variable. The most severe disease subtype is a rare neonatal form with death occurring before 1 year of age. {ECO:0000269|PubMed:10610716, ECO:0000269|PubMed:10993717, ECO:0000269|PubMed:11241842, ECO:0000269|PubMed:12638942, ECO:0000269|PubMed:16951918, ECO:0000269|PubMed:20609603, ECO:0000269|PubMed:21893389, ECO:0000269|PubMed:21982811, ECO:0000269|PubMed:26945816, ECO:0000269|PubMed:27411168, ECO:0000269|PubMed:8955159}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) [MIM:159950]: An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency. {ECO:0000269|PubMed:22703880, ECO:0000269|PubMed:24164096, ECO:0000269|PubMed:27026573, ECO:0000269|PubMed:33798445}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.5.1.-
uniprot
proteins
ec_number
3.5.1.109
uniprot
proteins
ec_number
3.5.1.23
uniprot
proteins
function
FUNCTION: Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:10610716, PubMed:11451951, PubMed:15655246, PubMed:26898341, PubMed:36752535, PubMed:7744740, PubMed:7852294). 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:15655246, PubMed:7744740). 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). Also has 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). {ECO:0000250|UniProtKB:Q9WV54, ECO:0000269|PubMed:10610716, ECO:0000269|PubMed:11451951, ECO:0000269|PubMed:12764132, ECO:0000269|PubMed:12815059, ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17713573, ECO:0000269|PubMed:22261821, ECO:0000269|PubMed:26898341, ECO:0000269|PubMed:36752535, ECO:0000269|PubMed:7744740, ECO:0000269|PubMed:7852294, ECO:0000303|PubMed:10610716}.; FUNCTION: [Isoform 2]: May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity. {ECO:0000305|PubMed:22927646}.
uniprot
proteins
mass_dalton
44660
uniprot
proteins
mutagenesis
MUTAGEN 80; /note="L->Q: No effect on autocatalytic processing, but loss of ceramidase activity, when associated with 165-Q--Q-167."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 141; /note="T->A: Decreased rate of autocatalytic processing."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 143; /note="C->A: Loss of autocatalytic processing. Loss of ceramidase activity."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 159; /note="R->Q: Strongly decreased autocatalytic processing. Moderately decreased ceramidase activity."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 162; /note="D->N: Strongly decreased autocatalytic processing. Strongly decreased ceramidase activity."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 165..167; /note="VFL->QFQ: No effect on autocatalytic processing, but loss of ceramidase activity, when associated with Q-80."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 169..171; /note="WNI->QNQ: Moderately decreased autocatalytic processing, but loss of ceramidase activity, when associated with Q-176."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 173; /note="N->Q: Loss of ceramide catabolic process."; /evidence="ECO:0000269|PubMed:11451951"; MUTAGEN 176; /note="W->Q: Moderately decreased autocatalytic processing, but loss of ceramidase activity, when associated with 169-Q--Q-171."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 195; /note="N->Q: No effect on ceramide catabolic process."; /evidence="ECO:0000269|PubMed:11451951"; MUTAGEN 259; /note="N->Q: Loss of ceramide catabolic process."; /evidence="ECO:0000269|PubMed:11451951"; MUTAGEN 286; /note="N->Q: No effect on ceramide catabolic process."; /evidence="ECO:0000269|PubMed:11451951"; MUTAGEN 320; /note="N->A: Strongly decreased autocatalytic processing. Mildly decreased ceramidase activity."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 328..330; /note="FFL->QQQ: No effect on autocatalytic processing, but strongly decreased ceramidase activity."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 333; /note="R->Q: Mildly decreased autocatalytic processing. Loss of ceramidase activity."; /evidence="ECO:0000269|PubMed:29692406"; MUTAGEN 342; /note="N->Q: Loss of ceramide catabolic process."; /evidence="ECO:0000269|PubMed:11451951"; MUTAGEN 348; /note="N->Q: No effect on ceramide catabolic process."; /evidence="ECO:0000269|PubMed:11451951
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; sphingolipid metabolism. {ECO:0000269|PubMed:10610716, ECO:0000269|PubMed:7744740}.
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:11451951, ECO:0000269|PubMed:29692406, ECO:0000269|PubMed:30525581, ECO:0000269|PubMed:8955159}.; PTM: Proteolytically cleaved into two chains alpha and beta that remain associated via a disulfide bond (PubMed:11451951, PubMed:29692406, PubMed:30525581, PubMed:7744740). Cleavage gives rise to a conformation change that activates the enzyme. The same catalytic Cys residue mediates the autoproteolytic cleavage and subsequent hydrolysis of lipid substrates (PubMed:29692406, PubMed:30525581). The beta chain may undergo an additional C-terminal processing (PubMed:12815059). {ECO:0000269|PubMed:11451951, ECO:0000269|PubMed:12815059, ECO:0000269|PubMed:29692406, ECO:0000269|PubMed:30525581, ECO:0000269|PubMed:7744740}.
uniprot
proteins
protein_family
Acid ceramidase family
uniprot
proteins
pubmed
10610716
uniprot
proteins
pubmed
10993717
uniprot
proteins
pubmed
11241842
uniprot
proteins
pubmed
11451951
uniprot
proteins
pubmed
12638942
uniprot
proteins
pubmed
12754519
uniprot
proteins
pubmed
12764132
uniprot
proteins
pubmed
12815059
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15655246
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16951918
uniprot
proteins
pubmed
17713573
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
20609603
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21893389
uniprot
proteins
pubmed
21982811
uniprot
proteins
pubmed
22261821
uniprot
proteins
pubmed
22703880
uniprot
proteins
pubmed
22927646
uniprot
proteins
pubmed
24164096
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26898341
uniprot
proteins
pubmed
26945816
uniprot
proteins
pubmed
27026573
uniprot
proteins
pubmed
27411168
uniprot
proteins
pubmed
29692406
uniprot
proteins
pubmed
30525581
uniprot
proteins
pubmed
33798445
uniprot
proteins
pubmed
36752535
uniprot
proteins
pubmed
7744740
uniprot
proteins
pubmed
7852294
uniprot
proteins
pubmed
8955159
uniprot
proteins
sequence_length
395
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:12764132}. Secreted {ECO:0000269|PubMed:7744740}. Note=Secretion is extremely low and localization to lysosomes is mannose-6-phosphate receptor-dependent. {ECO:0000269|PubMed:11451951}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000305|PubMed:22927646}. Cytoplasm {ECO:0000305|PubMed:22927646}. Note=A localization to the nucleus and the cytoplasm has also been reported for ASAH1, most probably for isoforms devoid of a signal peptide. {ECO:0000305|PubMed:22927646}.
uniprot
proteins