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Literature summary for 3.1.4.12 extracted from

  • Clarke, C.J.; Snook, C.F.; Tani, M.; Matmati, N.; Marchesini, N.; Hannun, Y.A.
    The extended family of neutral sphingomyelinases (2006), Biochemistry, 45, 11247-11256.
    View publication on PubMed

Activating Compound

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(Commentary)

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 (Commentary)

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

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

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

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

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 [Da] Molecular Weight Maximum [Da] Comment Organism
32000
-
x * 32000, SDS-PAGE Helicobacter pylori
47600
-
x * 47600, nSMase1, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

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

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 (Commentary)

Purification (Comment) Organism
native enzyme Helicobacter pylori

Reaction

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

Source Tissue Comment Organism Textmining
brain nSMase1, specific for Homo sapiens
-
fibroblast
-
Homo sapiens
-
hepatoma cell
-
Rattus norvegicus
-

Substrates and Products (Substrate)

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

Subunits Comment Organism
? x * 32000, SDS-PAGE Helicobacter pylori
? x * 47600, nSMase1, SDS-PAGE Homo sapiens

Synonyms

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

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