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Literature summary extracted from
- Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases (2011), Br. J. Pharmacol., 163, 694-712.
Activating Compound
| EC Number | Activating Compound | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.5.1.23 | ceramide-1-phosphate | activates neutral ceramidase | Homo sapiens |  |
| 3.5.1.23 | additional information | acid ceramidase requires anionic lysosomal lipids and saposin as cofactors for efficient hydrolysis of ceramide in vivo | Homo sapiens | |
| 3.5.1.23 | N-(4-hydroxyphenyl)retinamide | increases isoform ACER2 activity and mRNA, but not isoforms ACER1 or ACER3 | Homo sapiens | |
| 3.5.1.23 | sphingosine-1-phosphate | activates neutral ceramidase | Homo sapiens | |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 3.5.1.23 | acid ceramidase is expressed in Sf21 insect cells | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.5.1.23 | (1R,2R)-2-(N-tetradecanoylamino)-1-(4-nitrophenyl)-1,3-propanediol | potent inhibitor of acid ceramidase | Homo sapiens | |
| 3.5.1.23 | (1S, 2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol | inhibitor of alkaline ceramidase; inhibitor of alkaline ceramidase; inhibitor of neutral ceramidase | Homo sapiens | |
| 3.5.1.23 | CHAPS | inhibits in vitro neutral ceramidase activity | Homo sapiens | |
| 3.5.1.23 | Cu2+ | inhibitor of neutral ceramidase | Homo sapiens | |
| 3.5.1.23 | desipramine | inhibitor of acid ceramidase | Homo sapiens | |
| 3.5.1.23 | Fe2+ | inhibitor of neutral ceramidase | Homo sapiens | |
| 3.5.1.23 | glycodeoxycholate | inhibits in vitro neutral ceramidase activity | Homo sapiens | |
| 3.5.1.23 | LCL385 | inhibitor of acid ceramidase | Homo sapiens | |
| 3.5.1.23 | additional information | all stereoisomers of D-erythro-ceramide and sphingosine (L-threo, D-threo, and L-erythro isomers), N-methyl-D-erythro-sphingosine and D-erythro-urea-C16-ceramide show significant inhibitory effects on neural ceramidase; N-methyl ceramide, 1-O-methyl ceramide, cis-D-erythro ceramide or N,N-dimethyl-D-erythrosphingosine have no effect on neutral ceramidase | Homo sapiens | |
| 3.5.1.23 | N-oleoylethanolamine | low potency, inhibitor of acid ceramidase | Homo sapiens | |
| 3.5.1.23 | phosphatidylcholine | inhibitor of alkaline ceramidase; inhibitor of alkaline ceramidase; inhibitor of neutral ceramidase | Homo sapiens | |
| 3.5.1.23 | taurocholate | inhibits in vitro neutral ceramidase activity | Homo sapiens | |
| 3.5.1.23 | taurodeoxycholate | inhibits in vitro neutral ceramidase activity | Homo sapiens | |
| 3.5.1.23 | Zn2+ | inhibitor of neutral ceramidase | Homo sapiens | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 3.5.1.23 | endoplasmic reticulum | alkaline ceramidase | Homo sapiens | 5783 | - |
| 3.5.1.23 | extracellular | acid ceramidase | Homo sapiens | - |
- |
| 3.5.1.23 | extracellular | neutral ceramidase | Homo sapiens | - |
- |
| 3.5.1.23 | Golgi apparatus | alkaline ceramidase | Homo sapiens | 5794 | - |
| 3.5.1.23 | lysosome | acid ceramidase | Homo sapiens | 5764 | - |
| 3.5.1.23 | plasma membrane | neutral ceramidase | Homo sapiens | 5886 | - |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.5.1.23 | Ca2+ | ACER isoform activities are enhanced by Ca2+ | Homo sapiens | |
| 3.5.1.23 | additional information | neutral ceramidase is not affected by Ca2+, Mg2+ or Mn2+. No cations are required to activate neutral ceramidase | Homo sapiens |
Molecular Weight [Da]
| EC Number | Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|---|
| 3.5.1.23 | 31000 | - |
x * 31000, alkaline ceramidase, SDS-PAGE | Homo sapiens |
| 3.5.1.23 | 53000 | - |
x * 53000, acid ceramidase, SDS-PAGE | Homo sapiens |
| 3.5.1.23 | 116000 | - |
x * 116000, neutral ceramidase, SDS-PAGE | Homo sapiens |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.5.1.23 | additional information | Homo sapiens | only the natural D-erythro-ceramide isomer is used as substrate of the four stereoisomers of ceramide. Dihydroceramide or phytoceramide forms, shortening the length of the alkyl backbone, methylation of the primary or secondary hydroxyl groups results in reduction or loss of the neutral ceramidase activity | ? | - |
? | |
| 3.5.1.23 | additional information | Homo sapiens | short acyl-chain ceramides (i.e. C16 acyl chain) are poor substrates for acid ceramidase | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.5.1.23 | Homo sapiens | - |
- |
- |
| 3.5.1.23 | Homo sapiens | Q13510 | acid ceramidase ASAH1 | - |
| 3.5.1.23 | Homo sapiens | Q8TDN7 | alkaline ceramidase ASAH3 | - |
| 3.5.1.23 | Homo sapiens | Q9NR71 | neutral ceramidase ASAH2 | - |
Posttranslational Modification
| EC Number | Posttranslational Modification | Comment | Organism |
|---|---|---|---|
| 3.5.1.23 | glycoprotein | acid ceramidase has six potential N-glycosylation sites | Homo sapiens |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 3.5.1.23 | - |
Homo sapiens |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 3.5.1.23 | cerebellum | alkaline ceramidase | Homo sapiens | - |
| 3.5.1.23 | fibroblast | alkaline ceramidase | Homo sapiens | - |
| 3.5.1.23 | heart | high expression of neutral ceramidase | Homo sapiens | - |
| 3.5.1.23 | intestine | neutral ceramidase | Homo sapiens | - |
| 3.5.1.23 | keratinocyte | - |
Homo sapiens | - |
| 3.5.1.23 | kidney | high expression of neutral ceramidase | Homo sapiens | - |
| 3.5.1.23 | leukocyte | alkaline ceramidase | Homo sapiens | - |
| 3.5.1.23 | liver | high expression of neutral ceramidase | Homo sapiens | - |
| 3.5.1.23 | placenta | alkaline ceramidase | Homo sapiens | - |
| 3.5.1.23 | skin | alkaline ceramidase | Homo sapiens | - |
| 3.5.1.23 | urine | acid ceramidase | Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.5.1.23 | additional information | only the natural D-erythro-ceramide isomer is used as substrate of the four stereoisomers of ceramide. Dihydroceramide or phytoceramide forms, shortening the length of the alkyl backbone, methylation of the primary or secondary hydroxyl groups results in reduction or loss of the neutral ceramidase activity | Homo sapiens | ? | - |
? | |
| 3.5.1.23 | additional information | short acyl-chain ceramides (i.e. C16 acyl chain) are poor substrates for acid ceramidase | Homo sapiens | ? | - |
? | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 3.5.1.23 | ? | x * 116000, neutral ceramidase, SDS-PAGE | Homo sapiens |
| 3.5.1.23 | ? | x * 31000, alkaline ceramidase, SDS-PAGE | Homo sapiens |
| 3.5.1.23 | ? | x * 53000, acid ceramidase, SDS-PAGE | Homo sapiens |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.5.1.23 | aCDase | - |
Homo sapiens |
| 3.5.1.23 | ACER1 | gene name of alkaline ceramidase isoform | Homo sapiens |
| 3.5.1.23 | ACER2 | gene name of alkaline ceramidase isoform | Homo sapiens |
| 3.5.1.23 | ACER3 | gene name of alkaline ceramidase isoform | Homo sapiens |
| 3.5.1.23 | acid ceramidase | - |
Homo sapiens |
| 3.5.1.23 | alkaline ceramidase | - |
Homo sapiens |
| 3.5.1.23 | alkCDase | - |
Homo sapiens |
| 3.5.1.23 | ASAH1 | gene name of acid ceramidase | Homo sapiens |
| 3.5.1.23 | ASAH2 | gene name of neutral ceramidase | Homo sapiens |
| 3.5.1.23 | ASAH3 | gene name of alkaline ceramidase | Homo sapiens |
| 3.5.1.23 | nCDase | - |
Homo sapiens |
| 3.5.1.23 | neutral ceramidase | - |
Homo sapiens |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 3.5.1.23 | 4.5 | - |
acid ceramidase | Homo sapiens |
| 3.5.1.23 | 7 | 9 | neutral ceramidase | Homo sapiens |
| 3.5.1.23 | 8.5 | 9.5 | alkaline ceramidase | Homo sapiens |
Expression
| EC Number | Organism | Comment | Expression |
|---|---|---|---|
| 3.5.1.23 | Homo sapiens | interleukin-1beta increases the activity, mRNA levels and protein synthesis of acid ceramidase | up |
| 3.5.1.23 | Homo sapiens | interleukin-1beta increases the activity, mRNA levels and protein synthesis of neutral ceramidase | up |
| 3.5.1.23 | Homo sapiens | isoform ACER2 is upregulated in tumors | up |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 3.5.1.23 | malfunction | abnormal overexpression of acid ceramidase is related to tumor progression and protection from cell death, while deficiency of acid ceramidase results in Farber disease | Homo sapiens |
| 3.5.1.23 | physiological function | acid ceramidase activity enhances acid sphingomyelinase secretion | Homo sapiens |
| 3.5.1.23 | physiological function | intestinal secreted neutral ceramidase is involved in digestion of dietary sphingolipids | Homo sapiens |
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