Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | nSMase1 activity required reducing agents | Homo sapiens | |
additional information | nSMase2 is activated by anionic phospholipids | Homo sapiens | |
phosphatidylglycerol | activates nSMase2 | Homo sapiens | |
phosphatidylserine | activates nSMase2 | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
nSMase1, DNA and amino acid sequence determination and analysis | Homo sapiens |
nSMase2, DNA and amino acid sequence determination and analysis, overexpression of nSMase2 in DELTAISC1 yeast cells and in MCF-7 cells | Homo sapiens |
overexpression of nSMase1, the recombinant enzyme shows altered subcellular localization in the endoplasmic reticulum compared to the wild-type nSMase1 localized in the nucleus | Rattus norvegicus |
Crystallization (Comment) | Organism |
---|---|
nSMase, crystal structure and structure-function analysis | Listeria ivanovii |
nSMase, crystal structure of nSMase complexed with Ca2+, Co2+, or Mg2+, and structure-function analysis | Bacillus cereus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of SMase knockout mutants, the mutant strain is less virulent for mice than the wild-type strain using an infection model of the mouse mammary gland | Listeria ivanovii |
additional information | MCF-7 cells overexpressing nSMase2 exhibit clearly lower sphingomyelin and higher ceramide levels, especially of very long chain ceramides, which correlates with a decrease in the level of C24:0- and C24:1-SM species, than corresponding vector-transfected cells, RNAi inhibitors of nSMase2 inhibit the cytotoxic effects of amyloid-beta peptides | Homo sapiens |
additional information | mutation of the two histidines, His134 and His252, abolished enzyme activity | Bacillus cereus |
additional information | site-directed mutagenesis indicates that two histidine residues, His136 and His272, are essential for catalysis, overexpression of catalytically inactive nSMase1 has no effect on CD95-induced ceramide production | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
BeF2 | an unusual phosphate analogue | Bacillus cereus | |
Ca2+ | - |
Bacillus cereus | |
EDTA | - |
Bacillus cereus | |
GW4869 | specific inhibition | Homo sapiens | |
oxidized glutathione | reversible inhibition of nSMase1 | Homo sapiens | |
peroxynitrite | irreversible inhibition of nSMase1 | Homo sapiens | |
reactive oxygen species | reversible inhibition of nSMase1 | Homo sapiens | |
Sr2+ | - |
Bacillus cereus | |
Zn2+ | Zn2+ binding to the high-affinity site activates the enzyme and, conversely, binding to the low-affinity site inhibits the enzyme | Bacillus cereus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
endoplasmic reticulum | recombinant overexpressed nSMase1 | Rattus norvegicus | 5783 | - |
extracellular | nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells | Staphylococcus aureus | - |
- |
extracellular | nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells | Listeria ivanovii | - |
- |
extracellular | nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells | Bacillus cereus | - |
- |
membrane | - |
Rattus norvegicus | 16020 | - |
membrane | nSMase1 contains two putative transmembrane domains at the C-terminus | Homo sapiens | 16020 | - |
additional information | C-terminal region of nSMase2 harbors several motifs that may play a role in its localization | Homo sapiens | - |
- |
nucleus | endogenous nSMase1 | Rattus norvegicus | 5634 | - |
plasma membrane | nSMase1 contains two putative transmembrane domains at the C-terminus | Homo sapiens | 5886 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Rattus norvegicus | |
Mg2+ | required by N-SMase for activity | Staphylococcus aureus | |
Mg2+ | required by N-SMase for activity | Helicobacter pylori | |
Mg2+ | required by N-SMase for activity | Homo sapiens | |
Mg2+ | required by N-SMase for activity | Listeria ivanovii | |
Mg2+ | required by N-SMase for activity, residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity | Bacillus cereus | |
Mg2+ | required by nSMase1 for activity | Homo sapiens | |
additional information | metal binding structure, overview | Listeria ivanovii | |
additional information | metal binding structure, overview | Bacillus cereus | |
Zn2+ | Zn2+ binding to the high-affinity site activates the enzyme and, conversely, binding to the low-affinity site inhibits the enzyme | Bacillus cereus |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
32000 | - |
x * 32000, SDS-PAGE | Helicobacter pylori |
47600 | - |
x * 47600, nSMase1, SDS-PAGE | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Staphylococcus aureus | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
additional information | Helicobacter pylori | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
additional information | Listeria ivanovii | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
additional information | Bacillus cereus | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
additional information | Listeria ivanovii nSMase | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
additional information | Helicobacter pylori nSMase | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
additional information | Bacillus cereus nSMase | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | ? | - |
? | |
sphingomyelin + H2O | Staphylococcus aureus | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Rattus norvegicus | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Helicobacter pylori | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Homo sapiens | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Listeria ivanovii | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Bacillus cereus | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Homo sapiens | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview, signaling roles of nSMase2 implicated in apoptosis, inflammation, cell growth, and differentiation, and Alzheimer disease, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Listeria ivanovii nSMase | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Helicobacter pylori nSMase | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | Bacillus cereus nSMase | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | N-acylsphingosine + choline phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Bacillus cereus | P09599 | nSMase | - |
Bacillus cereus nSMase | P09599 | nSMase | - |
Helicobacter pylori | - |
nSMase | - |
Helicobacter pylori nSMase | - |
nSMase | - |
Homo sapiens | O60906 | nSMase1 or smpd2; nSMase1 or smpd2 | - |
Homo sapiens | Q9NY59 | nSMase2; nSMase2 | - |
Listeria ivanovii | Q9RLV9 | nSMase | - |
Listeria ivanovii nSMase | Q9RLV9 | nSMase | - |
Rattus norvegicus | - |
- |
- |
Staphylococcus aureus | - |
- |
- |
Purification (Comment) | Organism |
---|---|
native enzyme | Helicobacter pylori |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases | Rattus norvegicus | |
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases | Homo sapiens | |
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview | Bacillus cereus | |
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, histidine residues, His136 and His272, are essential for catalysis | Homo sapiens | |
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview | Staphylococcus aureus | |
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview | Helicobacter pylori | |
a sphingomyelin + H2O = a ceramide + phosphocholine | catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, structure-function analysis, overview | Listeria ivanovii |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | nSMase1, specific for | Homo sapiens | - |
fibroblast | - |
Homo sapiens | - |
hepatoma cell | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Staphylococcus aureus | ? | - |
? | |
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Helicobacter pylori | ? | - |
? | |
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Listeria ivanovii | ? | - |
? | |
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Bacillus cereus | ? | - |
? | |
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Listeria ivanovii nSMase | ? | - |
? | |
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Helicobacter pylori nSMase | ? | - |
? | |
additional information | cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview | Bacillus cereus nSMase | ? | - |
? | |
sphingomyelin + H2O | - |
Staphylococcus aureus | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | - |
Rattus norvegicus | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | - |
Helicobacter pylori | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | - |
Homo sapiens | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | - |
Listeria ivanovii | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Staphylococcus aureus | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Rattus norvegicus | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Helicobacter pylori | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Homo sapiens | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Listeria ivanovii | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Bacillus cereus | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview, signaling roles of nSMase2 implicated in apoptosis, inflammation, cell growth, and differentiation, and Alzheimer disease, overview | Homo sapiens | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | nSMase2 uses sphingomyelin preferentially as a substrate in vitro with no activity against lyso-PAF | Homo sapiens | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity | Bacillus cereus | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | - |
Listeria ivanovii nSMase | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Listeria ivanovii nSMase | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | - |
Helicobacter pylori nSMase | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Helicobacter pylori nSMase | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview | Bacillus cereus nSMase | N-acylsphingosine + choline phosphate | - |
? | |
sphingomyelin + H2O | residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity | Bacillus cereus nSMase | N-acylsphingosine + choline phosphate | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 32000, SDS-PAGE | Helicobacter pylori |
? | x * 47600, nSMase1, SDS-PAGE | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
N-SMase | - |
Staphylococcus aureus |
N-SMase | - |
Rattus norvegicus |
N-SMase | - |
Helicobacter pylori |
N-SMase | - |
Homo sapiens |
N-SMase | - |
Listeria ivanovii |
N-SMase | - |
Bacillus cereus |
neutral sphingomyelinase | - |
Staphylococcus aureus |
neutral sphingomyelinase | - |
Rattus norvegicus |
neutral sphingomyelinase | - |
Helicobacter pylori |
neutral sphingomyelinase | - |
Homo sapiens |
neutral sphingomyelinase | - |
Listeria ivanovii |
neutral sphingomyelinase | - |
Bacillus cereus |
nSMase1 | - |
Rattus norvegicus |
nSMase1 | - |
Homo sapiens |
nSMase2 | - |
Homo sapiens |
smdp3 | - |
Homo sapiens |
smpd2 | - |
Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
N-SMase | Staphylococcus aureus |
7.4 | - |
N-SMase | Rattus norvegicus |
7.4 | - |
N-SMase | Helicobacter pylori |
7.4 | - |
N-SMase | Homo sapiens |
7.4 | - |
N-SMase | Listeria ivanovii |
7.4 | - |
N-SMase | Bacillus cereus |