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Literature summary extracted from
- Neutral sphingomyelinases and nSMase2: bridging the gaps (2006), Biochim. Biophys. Acta, 1758, 1893-1901.
Activating Compound
| EC Number | Activating Compound | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.1.4.12 | additional information | nSMase2 is induced by TNFalpha, cytokines, cellular stresses such as UV-light, heat shock, apoptosis, and chemotherapeutic drugs, and by pathological stimuli such as amyloid-beta peptides and lipopolysaccharides | Homo sapiens | |
| 3.1.4.12 | protein kinase C-zeta | mediates the activation of N-SMase by 1,25-dihydroxyvitamin D3, while protein kinase C-delta inhibits the activation | Homo sapiens |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 3.1.4.12 | isozyme nSMase1 | Homo sapiens |
| 3.1.4.12 | isozymes nSMase1 and nSMase2, overexpression of nSMase2 increases the shpingomyelin metabolism while overexpression of nSMase1 has no effect | Mus musculus |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.1.4.12 | additional information | construction of nSMase2 and of nSMase1 knockout mice, the latter do not show lipid storage abnormalities nor deficient sphingomyelin metabolism, phenotype, overview | Mus musculus |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.1.4.12 | 3-O-methylsphingomyelin | - |
Bos taurus |  |
| 3.1.4.12 | 3-O-methylsphingomyelin | - |
Homo sapiens | |
| 3.1.4.12 | 3-O-methylsphingomyelin | - |
Mus musculus | |
| 3.1.4.12 | 3-O-methylsphingomyelin | - |
Rattus norvegicus | |
| 3.1.4.12 | C11AG | inhibits N-SMases in T-cells and macrophages | Homo sapiens | |
| 3.1.4.12 | GW4869 | noncompetitive | Homo sapiens | |
| 3.1.4.12 | manumycin A | - |
Homo sapiens | |
| 3.1.4.12 | additional information | protein kinase C-delta inhibits the activation of N-SMase by 1,25-dihydroxyvitamin D3 | Homo sapiens | |
| 3.1.4.12 | scyphostatin | isolated from Discomycetes, specifically inhibits N-SMases | Bos taurus | |
| 3.1.4.12 | scyphostatin | isolated from Discomycetes, specifically inhibits N-SMases | Homo sapiens | |
| 3.1.4.12 | scyphostatin | isolated from Discomycetes, specifically inhibits N-SMases | Mus musculus | |
| 3.1.4.12 | scyphostatin | isolated from Discomycetes, specifically inhibits N-SMases | Rattus norvegicus | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 3.1.4.12 | membrane | nSMase2 is predominantly membrane-bound | Homo sapiens | 16020 | - |
| 3.1.4.12 | plasma membrane | - |
Mus musculus | 5886 | - |
| 3.1.4.12 | plasma membrane | - |
Homo sapiens | 5886 | - |
| 3.1.4.12 | plasma membrane | - |
Rattus norvegicus | 5886 | - |
| 3.1.4.12 | plasma membrane | - |
Bos taurus | 5886 | - |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.1.4.12 | Mg2+ | nSMase2 is a Mg2+-dependent neutral sphingomyelinase | Mus musculus | |
| 3.1.4.12 | Mg2+ | nSMase2 is a Mg2+-dependent neutral sphingomyelinase | Homo sapiens | |
| 3.1.4.12 | Mg2+ | nSMase2 is a Mg2+-dependent neutral sphingomyelinase | Rattus norvegicus | |
| 3.1.4.12 | Mg2+ | nSMase2 is a Mg2+-dependent neutral sphingomyelinase | Bos taurus | |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.1.4.12 | sphingomyelin + H2O | Mus musculus | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | Homo sapiens | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | Rattus norvegicus | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | Bos taurus | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | N-acylsphingosine + choline phosphate | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.1.4.12 | Bos taurus | - |
multiple N-SMase isozymes, one of which is nSMase2 | - |
| 3.1.4.12 | Homo sapiens | - |
isozymes nSMase2 and nSMase1 | - |
| 3.1.4.12 | Mus musculus | - |
isozymes nSMase1 and nSMase2 | - |
| 3.1.4.12 | Rattus norvegicus | - |
- |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 3.1.4.12 | nSMase2 and nSMase3, from brain | Bos taurus |
| 3.1.4.12 | nSMase2, from brain | Rattus norvegicus |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 3.1.4.12 | brain | - |
Rattus norvegicus | - |
| 3.1.4.12 | brain | grey matter, high nSMase2 activity | Homo sapiens | - |
| 3.1.4.12 | brain | isozymes nSMase2 and nSMase3 | Bos taurus | - |
| 3.1.4.12 | heart | isozyme nSMase3 | Bos taurus | - |
| 3.1.4.12 | HL-60 cell | - |
Homo sapiens | - |
| 3.1.4.12 | liver | - |
Homo sapiens | - |
| 3.1.4.12 | LNCaP cell | - |
Homo sapiens | - |
| 3.1.4.12 | MCF-7 cell | - |
Homo sapiens | - |
| 3.1.4.12 | mesangial cell | - |
Rattus norvegicus | - |
| 3.1.4.12 | PC-12 cell | - |
Rattus norvegicus | - |
| 3.1.4.12 | skeletal muscle | isozyme nSMase3 | Bos taurus | - |
| 3.1.4.12 | spleen | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.1.4.12 | sphingomyelin + H2O | - |
Mus musculus | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | - |
Homo sapiens | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | - |
Rattus norvegicus | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | - |
Bos taurus | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | Mus musculus | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | Homo sapiens | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | Rattus norvegicus | N-acylsphingosine + choline phosphate | - |
? | |
| 3.1.4.12 | sphingomyelin + H2O | nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview | Bos taurus | N-acylsphingosine + choline phosphate | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.1.4.12 | N-SMase | - |
Mus musculus |
| 3.1.4.12 | N-SMase | - |
Homo sapiens |
| 3.1.4.12 | N-SMase | - |
Rattus norvegicus |
| 3.1.4.12 | N-SMase | - |
Bos taurus |
| 3.1.4.12 | neutral sphingomyelinase | - |
Mus musculus |
| 3.1.4.12 | neutral sphingomyelinase | - |
Homo sapiens |
| 3.1.4.12 | neutral sphingomyelinase | - |
Rattus norvegicus |
| 3.1.4.12 | neutral sphingomyelinase | - |
Bos taurus |
| 3.1.4.12 | nSMase2 | - |
Mus musculus |
| 3.1.4.12 | nSMase2 | - |
Homo sapiens |
| 3.1.4.12 | nSMase2 | - |
Rattus norvegicus |
| 3.1.4.12 | nSMase2 | - |
Bos taurus |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 3.1.4.12 | 7.4 | - |
nSMase2 | Homo sapiens |
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