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Literature summary for 3.5.1.23 extracted from
- Neutral ceramidase advances in mechanisms, cell regulation, and roles in cancer (2019), Adv. Biol. Regul., 71, 141-146 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression in insect cells of active truncated enzyme, consisting of the extracellular region (residues 99-780) and lacking the short intracellular region (residues 1-12), the transmembrane domain (residues 12-34), and the flexible O-glycosylated mucin box (residues 34-99) | Homo sapiens |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| crystallization of recombinant truncated enzyme, X-ray diffraction structure determination and analysis at 2.6 A resolution | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | ATRA downregulates nCDase expression at the message level results in less protein and activity in SH-SY5Y neuroblastoma cells | Homo sapiens |
| additional information | generation of nCDase deficient mice | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| endosome | - |
Rattus norvegicus | 5768 | - |
| endosome | - |
Homo sapiens | 5768 | - |
| endosome | - |
Mus musculus | 5768 | - |
| Golgi apparatus | - |
Rattus norvegicus | 5794 | - |
| Golgi apparatus | - |
Homo sapiens | 5794 | - |
| Golgi apparatus | - |
Mus musculus | 5794 | - |
| microsome | - |
Rattus norvegicus | - |
- |
| microsome | - |
Homo sapiens | - |
- |
| microsome | - |
Mus musculus | - |
- |
| microsome | - |
Nilaparvata lugens | - |
- |
| mitochondrion | - |
Rattus norvegicus | 5739 | - |
| mitochondrion | - |
Homo sapiens | 5739 | - |
| mitochondrion | - |
Mus musculus | 5739 | - |
| plasma membrane | - |
Rattus norvegicus | 5886 | - |
| plasma membrane | - |
Homo sapiens | 5886 | - |
| plasma membrane | - |
Mus musculus | 5886 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | binding structure analysis | Homo sapiens |  |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Amorphophallus muelleri | A0A2D1WBF2 | - |
- |
| Homo sapiens | Q9NR71 | - |
- |
| Mus musculus | Q9JHE3 | - |
- |
| Nilaparvata lugens | - |
- |
- |
| Rattus norvegicus | Q91XT9 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| native enzyme from brain | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Rattus norvegicus | - |
| brain | - |
Homo sapiens | - |
| brain | - |
Mus musculus | - |
| colon | - |
Rattus norvegicus | - |
| colon | - |
Mus musculus | - |
| colon | high expression | Homo sapiens | - |
| colorectal cancer cell | - |
Homo sapiens | - |
| H4-II-E-C3 cell | - |
Rattus norvegicus | - |
| heart | - |
Rattus norvegicus | - |
| heart | - |
Homo sapiens | - |
| heart | - |
Mus musculus | - |
| hepatocyte | - |
Rattus norvegicus | - |
| INS-1 cell | - |
Rattus norvegicus | - |
| keratinocyte | - |
Homo sapiens | - |
| kidney | - |
Rattus norvegicus | - |
| kidney | - |
Mus musculus | - |
| kidney | high expression | Homo sapiens | - |
| liver | - |
Rattus norvegicus | - |
| liver | - |
Mus musculus | - |
| liver | high expression | Homo sapiens | - |
| lung | - |
Rattus norvegicus | - |
| lung | - |
Homo sapiens | - |
| lung | - |
Mus musculus | - |
| MEF cell | mouse embryonic fibroblast | Rattus norvegicus | - |
| MEF cell | mouse embryonic fibroblast | Mus musculus | - |
| neuroblastoma cell | - |
Rattus norvegicus | - |
| neuroblastoma cell | - |
Homo sapiens | - |
| neuroblastoma cell | - |
Mus musculus | - |
| pancreatic beta cell | - |
Rattus norvegicus | - |
| pancreatic islet | - |
Rattus norvegicus | - |
| SH-SY5Y cell | - |
Rattus norvegicus | - |
| SH-SY5Y cell | - |
Homo sapiens | - |
| SH-SY5Y cell | - |
Mus musculus | - |
| small intestine | - |
Rattus norvegicus | - |
| small intestine | - |
Mus musculus | - |
| small intestine | high expression | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| C12:0-ceramide + H2O | preferred substrate | Nilaparvata lugens | laurate + sphingosine | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | the overall structure showed a catalytic domain (residues 99-626), a short linker (627-641), and an immunoglobulin (IG)-like domain (642-780). In comparison with the distantly homologous bacterial CDase (bCDase), in the human nCDase, a 30-residue subdomain insert replaces a 6-residue span of bCDase. This insertion seems to stabilize two alpha helixes of the active site. This subdomain conformation is aided by two internal disulfide bridges, formed by four cysteines that are conserved in eukaryotes | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ASAH2B | - |
Homo sapiens |
| ASAH2B | - |
Mus musculus |
| N-acylsphingosine amidohydrolase 2 | - |
Homo sapiens |
| N-acylsphingosine amidohydrolase 2 | - |
Mus musculus |
| nCDase | - |
Rattus norvegicus |
| nCDase | - |
Homo sapiens |
| nCDase | - |
Mus musculus |
| nCDase | - |
Nilaparvata lugens |
| nCDase | - |
Amorphophallus muelleri |
| neutral ceramidase | - |
Rattus norvegicus |
| neutral ceramidase | - |
Homo sapiens |
| neutral ceramidase | - |
Mus musculus |
| neutral ceramidase | - |
Nilaparvata lugens |
| neutral ceramidase | - |
Amorphophallus muelleri |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 6 | - |
- |
Nilaparvata lugens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | distant homologues from nCDase are found in taxa all over evolution reinforcing a crucial role for ceramide | Rattus norvegicus |
| evolution | distant homologues from nCDase are found in taxa all over evolution reinforcing a crucial role for ceramide | Homo sapiens |
| evolution | distant homologues from nCDase are found in taxa all over evolution reinforcing a crucial role for ceramide | Mus musculus |
| evolution | distant homologues from nCDase are found in taxa all over evolution reinforcing a crucial role for ceramide | Nilaparvata lugens |
| evolution | distant homologues from nCDase are found in taxa all over evolution reinforcing a crucial role for ceramide | Amorphophallus muelleri |
| malfunction | nCDase deficient mice are viable with no obvious deficiency under normal breeding conditions. Further investigation reveals that nCDase deficient mice are not able to degrade dietary sphingolipids. Gemcitabine treated cells show an increase of the levels of specific ceramides, attributed to a reduction of nCDase expression. The increased ceramide is also implicated in suppression of cell growth. nCDase deficient mice treated with DSS show a paradoxical elevation of sphingosine and an increase of sphingosine 1-phosphate. Knockout mice are partly protected from brain injury. MEFs from nCDase deficient mice present an increase of autophagic flux and more specifically mitophagy when subjected to the 2DG/AA model of necroptosis. They showed as well that inhibition of autophagy reverses this phenotype. Inhibition of nCDase may enhance cell survival by increasing the clearance of damaged mitochondria via mitophagy | Mus musculus |
| malfunction | nCDase downregulation induces a decrease of cell growth and neuronal differentiation. Gemcitabine treated cells show an increase of the levels of specific ceramides, attributed to a reduction of nCDase expression. The increased ceramide is also implicated in suppression of cell growth. UVB irradiation decreases nCDase activity in keratinocytes, and ceramidase inhibition or siRNA-mediated suppression sensitizes keratinocytes to low-dose-UVB-induced apoptosis. ATRA downregulated nCDase expression at the message level results in less protein and activity in SH-SY5Y neuroblastoma cells. Inhibition of nCDase in colorectal cancer (CRC) cells induces a decrease of phosphorylation of GSK3beta, which activates the kinase. In turn, activated GSK3beta phosphorylated beta-catenin, resulting in a significant decrease in its levels. Inhibition of nCDase results in dephosphorylation and inactivation of Akt, which is responsible for the loss of phosphorylation of GSK3beta and the loss of beta-catenin. Cells overexpressing nCDase are protected from cell death induced by the short chain C6-ceramide | Homo sapiens |
| malfunction | NS-1 cell nCDase-containing exosomes block apoptosis induced by palmitate | Rattus norvegicus |
| malfunction | the knockdown of this enzyme enhances survival of the female planthopper at high (32°C) or low (22°C) temperature | Nilaparvata lugens |
| additional information | possible mechanism for the catabolism of ceramide by the enzyme. The active site of human neutral ceramidase is a narrow, 20 A deep, hydrophobic pocket with a Zn2+ ion at the base. Hydrophobic residues line the pocket from outside to inside with one side of the active site cavity formed by the ny2-alpha8 helices. His196, Arg257, Tyr579, and Tyr591 were identified as playing critical roles in catalysis and stabilizing the transition state of ceramide hydrolysis, proposed model of ceramide hydrolysis by nCDase in membranes, overview. The membrane-tethered human nCDase involves extracting ceramide from membranes (left) or bile-acid micelles (right) into the deep hydrophobic pocket. The flexible tether allows human nCDase to hydrolyze ceramide in two different physiological forms | Homo sapiens |
| physiological function | nCDase regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. CDase may protect against inflammation using a dextran sodium sulfate (DSS) mouse model. Role of nCDase in traumatic brain injury | Mus musculus |
| physiological function | nCDase regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. Exosomes expressing nCDase can protect INS-1 cells or rat primary Langerhans islets against apoptosis induced by high dose cytokines | Rattus norvegicus |
| physiological function | nCDase regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. Role of nCDase in traumatic brain injury. The enzyme is involved in intracellular signaling | Homo sapiens |
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Release 2023.1 (January 2023)
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