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1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
1,2-dioleoyl-sn-glycero-3-phosphocholine + H2O
?
0.7% activity compared to sphingomyelin
-
-
?
1-alkyl-lyso-platelet activating factor + H2O
1-alkylglycerol + choline phosphate
-
-
-
?
1-O-octadecyl-2-lyso-platelet-activating factor + H2O
1-O-octadecyl-sn-glycerol + phosphocholine
very little activity
-
-
?
2-(N-hexadecanoylamino)-4-nitrophenylphosphorylcholine + H2O
2-(N-hexadecanoylamino)-4-nitrophenol + choline phosphate
-
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine + H2O
?
4-nitrobenz-2-oxa-1,3-diazole-sphingosylphosphorylcholine + H2O
4-nitrobenz-2-oxa-1,3-diazole-sphingosine + choline phosphate
-
-
-
?
4-nitrophenyl phosphorylcholine + H2O
4-nitrophenol + phosphorylcholine
6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-hexanoyl)sphingosyl phosphocholine + H2O
6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-N-hexanoylsphingosine + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphocholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + phosphorylcholine
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
a sphingomyelin + H2O
a ceramide + phosphocholine
ADP + H2O
AMP + phosphate
-
-
-
?
ADP-ribose + H2O
?
-
-
-
?
ATP + H2O
ADP + phosphate
-
-
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
bis(4-nitrophenyl)phosphate + H2O
?
bis-p-nitrophenyl phosphate + H2O
?
BODIPY FL C12-sphingomyelin + H2O
BODIPY FL C12-ceramide + phosphocholine
-
-
-
-
?
C6-7-nitro-2-1,3-benzoxadiazol-4-yl-sphingomyelin + H2O
?
-
-
-
?
CDP-choline + H2O
CMP + phosphocholine
-
-
-
?
CDP-choline + H2O
CMP + phosphorylcholine
-
-
-
?
CDP-ethanolamine + H2O
CMP + phosphoethanolamine
-
-
-
?
ceramide 1-phosphate + H2O
?
-
-
-
-
?
choline-methyl-sphingomyelin + H2O
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
L-alpha-phosphatidylinositol + H2O
?
5.63% activity compared to sphingomyelin
-
-
?
lissamine-rhodamine dodecanoyl sphingosyl phosphocholine + H2O
?
-
neutral sphingomyelinase
-
-
?
lyso-phosphatidylcholine + H2O
?
-
-
-
-
?
lyso-platelet-activating factor + H2O
1-alkylglycerol + choline phosphate
-
103fold higher activity than with sphingomyelin in the absence of detergent
-
?
lyso-platelet-activating factor + H2O
alkylglycerol + choline phosphate
-
55% of activity with sphingomyelin in the absence of detergent
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
N-dodecanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-dodecanoylsphingosine + choline phosphate
-
-
-
?
N-hexanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-hexanoylsphingosine + choline phosphate
-
-
-
?
N-methyl-sphingomyelin + H2O
N-methyl-N-acylsphingosine + choline phosphate
-
-
-
-
?
N-methylsphingomyelin + H2O
?
N-[[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-hexanoyl]-sphingosine-1-phosphocholine + H2O
N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphingosine + phosphorylcholine
-
-
-
?
p-nitrophenylphosphorylcholine + H2O
choline phosphate + p-nitrophenol
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
-
low activity
-
?
phosphatidylethanolamine + H2O
diacylglycerol + phosphorylethanolamine
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
sphingomyelin + H2O
ceramide + phosphocholine
sphingomyelin + H2O
ceramide + phosphorylcholine
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
sphingosylphosphorylcholine + H2O
sphingosine + choline phosphate
-
25% of activity with sphingomyelin
-
?
additional information
?
-
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
2.11% activity compared to sphingomyelin
-
-
?
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
2.11% activity compared to sphingomyelin
-
-
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
9.04% activity compared to sphingomyelin
-
-
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
9.04% activity compared to sphingomyelin
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
4.93% activity compared to sphingomyelin
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
4.93% activity compared to sphingomyelin
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine + H2O
?
-
-
-
-
?
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine + H2O
?
-
-
-
-
?
4-nitrophenyl phosphorylcholine + H2O
4-nitrophenol + phosphorylcholine
-
-
-
-
?
4-nitrophenyl phosphorylcholine + H2O
4-nitrophenol + phosphorylcholine
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine, ceramide colocalizes with acetylated tubulin in primary cilia and the mitotic spindle of human embryonic stem cells
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
i.e. an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
6-N-(7-nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
using radiolabelled C12-sphingomyelin as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
using the fluorescent substrate BODIPY-FL-C12-SM, i.e. N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, D-7711
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
6-N-(7-N´nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
using the fluorescent substrate BODIPY-FL-C12-SM, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, or D-7711
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
-
-
-
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
-
-
-
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
-
poor substrate
-
-
?
bis(4-nitrophenyl)phosphate + H2O
?
-
-
-
?
bis(4-nitrophenyl)phosphate + H2O
?
-
-
-
?
bis(4-nitrophenyl)phosphate + H2O
?
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
-
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
-
poor substrate
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
-
poor substrate
-
-
?
choline-methyl-sphingomyelin + H2O
?
high activity
-
-
?
choline-methyl-sphingomyelin + H2O
?
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
-
-
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
-
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
198fold higher activity than with sphingomyelin in the absence of detergent
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
580% of activity with sphingomyelin in the absence of detergent
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
8% of activity with sphingomyelin
-
?
N-methylsphingomyelin + H2O
?
-
-
-
-
?
N-methylsphingomyelin + H2O
?
-
-
-
-
?
N-methylsphingomyelin + H2O
?
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
8% of activity with sphingomyelin
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
-
in the presence of 0.08% sodium taurodeoxycholate
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
-
in the absence of detergents an in the presence of 0.05% Nonidet P-40
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
-
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
-
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
135146, 135147, 135148, 135149, 135150, 135153, 135156, 135159, 135160, 135161, 135168, 135169, 135187 -
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
the enzyme is active towards sphingomyelin species with a range of fatty acid chain lengths (C16-C24)
-
-
?
sphingomyelin + H2O
ceramide + phosphorylcholine
-
-
-
?
sphingomyelin + H2O
ceramide + phosphorylcholine
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
cholesterol activation of sphingomyelinase and the strong affinity of cholesterol for sphingomyelin allows the rapid, localized and self-contained production of the metabolic signal ceramide in specific microdomains
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
hydrolysis of sphingomyelin dispersed in diheptanoylphosphatidyl-choline. Premicellar complexes of sphingomyelinase mediate enzyme exchange for the stationary phase turnover
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
changes in the initial composition and topography of mixed monolayers of sphingomyelin and ceramide modulate the sphingomyelin degradation by the enzyme, overview, the enzyme in an extracellular toxin that exhibits potent hemolytic activity against sphingomyelin-rich erythrocytes in mammals
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
SMase shows very low activity against condensed sphingomyelin, but is active on loosely organized sphingomyelin in bilayers and monolayers, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid sphingomyelinase is involved in ceramide signaling, which is important in the lipid raft clustering and formation of redox signaling platform in cell membranes, overview, reactive oxygen species derived from ASM/ceramide triggered lipid raft redox signaling platforms can feedback regulate the ASM activity, FasL-induced O2- may be involved in this regulatory mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
the enzyme is important in the ceramide catabolism, overview
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
663974, 664216, 677818, 677875, 678250, 678375, 678939, 679144, 679604, 679649, 679682, 679685, 680745, 680754, 680767, 681259, 681266, 681322, 682246, 682477, 682983, 691060, 691456, 692009, 692236, 692274, 694111, 694201, 694260, 694284, 705457, 705473 -
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
very low activity in the absence of detergent
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma. Mutations of the enzyme found in colon cancer cells. IN the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the sap-like domain of human acid sphingomyelinase has activator-like functions, as well as importance as an integral part of acid spingomyelinase required for normal enzyme activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid SMase is involved in colonic cancer development and apoptosis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview, dietary SM inhibits colonic carcinogenesis by a mechanism related to SM digestion in the gut, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
degradation of sphingomyelin
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
exogenous sphingomyelinase causes impaired intestinal epithelial barrier function, Caco-2 cell monolayers are used as in vitro model for the intestinal barrier, exogenous sphingomyelinase increases transepithelial permeability and decreases transepithelial resistance at concentrations as low as 0.01 U/ml, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
secretory sphingomyelinase is upregulated in chronic heart failure, S-SMase further correlates with reduced skeletal quadriceps muscle strength as well as impaired peripheral vasodilator capacity, physiological function and parameters of S-SMase in heart tissue, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
nSMase2 uses sphingomyelin preferentially as a substrate in vitro with no activity against lyso-PAF
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
678375, 679649, 680063, 680143, 690455, 691696, 692073, 693467, 693810, 694904, 701641 -
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
A-SMase in the outer epidermis is essential for basal permeability function, A-SMase activity in the lower epidermis is involved in basal permeability barrier homeostasis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is important in ceramide metabolism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
SMase C causes hemolysis and thus is suspected to be a potential virulence factor
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
663974, 678083, 678142, 678375, 679649, 680065, 681268, 681322, 702696, 703199, 705473 -
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
D-erythrosphingosine or dihydroxysphingosine configuration of sphingomyelin results in a 3-5fold faster hydrolysis in comparison to a D-threo or L-erythro configuration
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
erythro-isomers of DL-trans-2-N-palmitoyl-1-O-phosphorylcholinesphingosine or dihydrosphingosine hydrolyzed faster than the threo-isomer
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
age-related increase in the activity of NSMase-2 is responsible for the interleukin-1beta hyperresponsiveness and a decrease in GSH levels, phenotype, regulation of neutral sphingomyelinase-2 by GSH in oxidative stress in aging-associated inflammation, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, and hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
DL-erythro-N-palmitoylsphingophosphorylcholine, N-stearylsphingophosphorylcholine, N-lignocerylsphingophosphorylcholine in monomolecular layers
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
100% activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
100% activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
127fold higher activity than with sphingomyelin in the absence of detergent
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
980% of activity with sphingomyelin in the absence of detergent
-
?
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
-
-
?
additional information
?
-
-
exogenous neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
?
additional information
?
-
-
sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion at a step in the fusion process after CD4 engagement, but sphingomyelinase treatment of cells does not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis, and furthermore, sphingomyelinase treatment does not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, Smase treatment does not influence Triton X-100 extraction of HIV-1 receptor proteins, overview
-
-
?
additional information
?
-
-
Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
-
-
?
additional information
?
-
-
the enzyme's beta-hairpin site directly binds to gangliosides, especially ganglioside GM3, i,e, NeuAca2-3Galbeta1-4Glcbeta1-1ceramide through a carbohydrate moiety. Binding response of the enzyme to liposomes containing GM3 is about 15fold higher than that to liposomes lacking GM3. Residues Trp-284 and Phe-285 in the beta-hairpin play an important role in the interaction with GM3
-
-
?
additional information
?
-
-
the enzyme's beta-hairpin site directly binds to gangliosides, especially ganglioside GM3, i,e, NeuAca2-3Galbeta1-4Glcbeta1-1ceramide through a carbohydrate moiety. Binding response of the enzyme to liposomes containing GM3 is about 15fold higher than that to liposomes lacking GM3. Residues Trp-284 and Phe-285 in the beta-hairpin play an important role in the interaction with GM3
-
-
?
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
-
-
?
additional information
?
-
-
acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
-
-
?
additional information
?
-
-
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
?
additional information
?
-
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
?
additional information
?
-
-
SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
-
-
?
additional information
?
-
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
?
additional information
?
-
-
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
?
additional information
?
-
the enzyme has no activity against choline-methyl-phosphatidylcholine
-
-
?
additional information
?
-
-
the enzyme has no activity against choline-methyl-phosphatidylcholine
-
-
?
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
-
-
?
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
-
-
?
additional information
?
-
-
acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
-
-
?
additional information
?
-
-
an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
-
-
?
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
?
additional information
?
-
-
Niemann Pick disease is an autosomal recessive disorder due to the deficit of lysosomal acid sphingomyelinase, which results in intracellular accumulation of sphingomyelin. Identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
-
-
?
additional information
?
-
-
nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
-
-
?
additional information
?
-
-
patients with atopic dermatitis show reduced activities of acid and neutral sphingomyelinase. The reduced acid sphingomyelinase activity may be partially responsible for the reduced content of stratum corneum ceramides. Reduced neutral sphingomyelinase activity may lead to changes in signal transduction, thereby regulating differentiation. The resulting reduction in involucrin could cause the reduced number of covalently bound ceramides in atopic dermatitis
-
-
?
additional information
?
-
-
spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
-
-
?
additional information
?
-
-
UV light-triggered ASMase activation is essentially required for bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac
-
-
?
additional information
?
-
-
a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
-
-
?
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
?
additional information
?
-
-
common polymorphisms of the SMPD1 gene occur in Niemann-Pick disease type A and B, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
-
-
?
additional information
?
-
-
exogenous acidic sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
?
additional information
?
-
-
exposure to the NO donors promotes an increase in the protein-protein interaction between acidic sphingomyelinase and caspase-3, with aSMase sequestering caspase-3 and preventing its cleavage and inhibiting apoptosis, overview
-
-
?
additional information
?
-
-
many signaling molecules involved in the pathogenesis of intestinal epithelial barrier, such as TNF-alpha or IFN-gamma, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases
-
-
?
additional information
?
-
-
neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors are essentially involved in endothelial nitric oxide synthase activation by tumor necrosis factor alpha, regulation of the pathway, overview
-
-
?
additional information
?
-
-
neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
-
-
?
additional information
?
-
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, different oxidants modulate different enzymes of the ceramide generating machinery to induce apoptosis in airway epithelial cells, overview
-
-
?
additional information
?
-
-
role for nSMase2 in pro-inflammatory responses induced by TNF-alpha as a regulator of adhesion proteins, both p38-alpha MAPK and nSMase2 are involved in the TNF-alpha-stimulated up-regulation of the adhesion proteins vascular cell adhesion molecule-1 and intercellular adhesion molecule-1
-
-
?
additional information
?
-
-
structural-functional properties of its carboxyl-terminus, amino acids 462-629, the carboxyl-terminus of the ASM is crucial for its protein structure, which in turns dictates the enzymatic function and secretion, overview
-
-
?
additional information
?
-
wild-type alkaline sphingomyelinase inhibits colonic tumorigenesis, while enzyme deficiency or aberrant enzyme forms are associated with human liver tumorigenesis, the enzyme activity is increased in cholestatic liver disease excluding primary sclerosing cholangitis, overview
-
-
?
additional information
?
-
-
wild-type alkaline sphingomyelinase inhibits colonic tumorigenesis, while enzyme deficiency or aberrant enzyme forms are associated with human liver tumorigenesis, the enzyme activity is increased in cholestatic liver disease excluding primary sclerosing cholangitis, overview
-
-
?
additional information
?
-
-
ASM is necessary for stress-induced cell death
-
-
?
additional information
?
-
-
the specific ligand binding activity of the serotonin1A receptor in membranes isolated from CHO-5-HT1AR cells is increased upon sphingomyelinase treatment (25 or 50 mU/ml) for 90 min in DMEM/F-12 medium under serum free condition
-
-
?
additional information
?
-
-
establishment of a sensitive quantitative assay method using the fluorescent substrate BODIPY-FL-C12-SM, i.e. N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, D-7711
-
-
?
additional information
?
-
no activity with 4-nitrophenyl-TMP
-
-
?
additional information
?
-
-
no activity with 4-nitrophenyl-TMP
-
-
?
additional information
?
-
no activity with sphingomyelin or AMP
-
-
?
additional information
?
-
-
no activity with sphingomyelin or AMP
-
-
?
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
-
-
?
additional information
?
-
the enzyme is a virulence factor
-
-
?
additional information
?
-
-
the enzyme is a virulence factor
-
-
?
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
-
-
?
additional information
?
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
?
additional information
?
-
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
?
additional information
?
-
-
modification of the SMase/SM-synthase balance, shown in the nuclei 1 h after serum deprivation, appears specific for the early events of the apoptotic process
-
-
?
additional information
?
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
?
additional information
?
-
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
?
additional information
?
-
-
spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
-
-
?
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
?
additional information
?
-
-
ASMase inhibition decreases ceramide generation during ischemia/reperfusion, and attenuates serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation, overview, the enzyme is involved in hepatic ischemia/reperfusion damage, ceramide generated from ASMase plays a key role in I/R-induced liver damage, molecular mechanisms, overview
-
-
?
additional information
?
-
-
ASMase activity is required for an efficient fusion of late phagosomes with lysosomes including the efficient transfer of lysosomal hydrolases into phagosomes containing Listeria monocytogenes
-
-
?
additional information
?
-
-
Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
-
-
?
additional information
?
-
-
Src kinase-dependent phosphorylation of p38 MAPK is involved in P2X7-induced A-SMase activation, A-SMase mediates ATP receptor P2X7R-dependent microparticle shedding and P2X7-dependent IL-1beta release
-
-
?
additional information
?
-
-
establishment of a sensitive quantitative assay method using the fluorescent substrate BODIPY-FL-C12-SM, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, or D-7711
-
-
?
additional information
?
-
no activity with AMP and diadenosine tetraphosphate
-
-
?
additional information
?
-
-
no activity with AMP and diadenosine tetraphosphate
-
-
?
additional information
?
-
the soluble enzyme form that lacks the GPI moiety responsible for anchoring SMPDL3B to the cell surface displays no head group hydrolysis with the following substrates: sphingomyelin in Triton X-100 micelles, sphingomyelin in neutral liposomes (also comprising phosphatidylcholine and cholesterol), the soluble micelle-forming lipids sphingosylphosphorylcholine, and platelet-activating factor
-
-
?
additional information
?
-
-
the soluble enzyme form that lacks the GPI moiety responsible for anchoring SMPDL3B to the cell surface displays no head group hydrolysis with the following substrates: sphingomyelin in Triton X-100 micelles, sphingomyelin in neutral liposomes (also comprising phosphatidylcholine and cholesterol), the soluble micelle-forming lipids sphingosylphosphorylcholine, and platelet-activating factor
-
-
?
additional information
?
-
-
The sphingomyelinase, but not the phospholipase C activity, is essential for induction of hot-cold hemolysis in human erythrocytes, that contain both phosphatidylcholine and sphingomyelin but also in goat erythrocytes, which lack phosphatidylcholine, however, in horse erythrocytes, with a large proportion of phosphatidylcholine and almost no sphingomyelin, hot-cold hemolysis induced by PlcHR2 is not observed, overview. Sphingomyelinase activity gives rise to the formation of ceramide-rich, rigid membrane domains that are resistant to Triton X-100 solubilization
-
-
?
additional information
?
-
-
PlcHR2 toxin from Pseudomonas aeruginosa is an enzyme with both phospholipase C and sphingomyelinase activities, PlcHR2 hydrolyzes phosphatidylcholine and sphingomyelin at similar rates, but other phospholipids are cleaved at much lower rates, if at all
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
?
additional information
?
-
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
-
-
?
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
?
additional information
?
-
-
neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
-
-
?
additional information
?
-
-
a phosphatidylcholine/sphingomyelin metabolism crosstalk which regulates the intranuclear ceramide/diacylglycerol pool exists in the chromatin structure, effect of phosphatidylcholine-specific phospholipase C activity on neutral sphingomyelinase and reverse sphingomyelin synthase, which enrich the intranuclear ceramide pool, overview
-
-
?
additional information
?
-
-
aging in rats causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2, NSMase-2 is both required and sufficient for the onset of IL-1beta hyperresponsiveness during aging, overview
-
-
?
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
?
additional information
?
-
-
neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats and is a key event in glutathione repletion, overview
-
-
?
additional information
?
-
-
the enzyme is involved in sphingomyelin digestion
-
-
?
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
?
additional information
?
-
-
-
-
-
?
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
-
-
?
additional information
?
-
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
?
additional information
?
-
-
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
?
additional information
?
-
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
substrate specificity, the enzyme is highly sphingomyelin-specific, it may not have sphingomyelinase D activity, because it does not hydrolyze the ester linkage between ceramide phosphate and choline. Of the phospholipids tested, the enzyme hydrolyzes only the ester linkage between ceramide and phosphocholine and has no activity toward phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine and phosphatidylinositol
-
-
?
additional information
?
-
substrate specificity, the enzyme is highly sphingomyelin-specific, it may not have sphingomyelinase D activity, because it does not hydrolyze the ester linkage between ceramide phosphate and choline. Of the phospholipids tested, the enzyme hydrolyzes only the ester linkage between ceramide and phosphocholine and has no activity toward phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine and phosphatidylinositol
-
-
?
additional information
?
-
-
the enzyme is inactive towards sphingosine 1-phosphate and phosphatidylcholine
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
a sphingomyelin + H2O
a ceramide + choline phosphate
a sphingomyelin + H2O
a ceramide + phosphocholine
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
-
low activity
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
sphingomyelin + H2O
ceramide + phosphocholine
sphingomyelin + H2O
ceramide + phosphorylcholine
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
additional information
?
-
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine, ceramide colocalizes with acetylated tubulin in primary cilia and the mitotic spindle of human embryonic stem cells
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
135146, 135147, 135148, 135149, 135150, 135153, 135156, 135159, 135160, 135161, 135168, 135169, 135187 -
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
?
sphingomyelin + H2O
ceramide + phosphocholine
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
cholesterol activation of sphingomyelinase and the strong affinity of cholesterol for sphingomyelin allows the rapid, localized and self-contained production of the metabolic signal ceramide in specific microdomains
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
changes in the initial composition and topography of mixed monolayers of sphingomyelin and ceramide modulate the sphingomyelin degradation by the enzyme, overview, the enzyme in an extracellular toxin that exhibits potent hemolytic activity against sphingomyelin-rich erythrocytes in mammals
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid sphingomyelinase is involved in ceramide signaling, which is important in the lipid raft clustering and formation of redox signaling platform in cell membranes, overview, reactive oxygen species derived from ASM/ceramide triggered lipid raft redox signaling platforms can feedback regulate the ASM activity, FasL-induced O2- may be involved in this regulatory mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
the enzyme is important in the ceramide catabolism, overview
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma. Mutations of the enzyme found in colon cancer cells. IN the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid SMase is involved in colonic cancer development and apoptosis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview, dietary SM inhibits colonic carcinogenesis by a mechanism related to SM digestion in the gut, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
degradation of sphingomyelin
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
exogenous sphingomyelinase causes impaired intestinal epithelial barrier function, Caco-2 cell monolayers are used as in vitro model for the intestinal barrier, exogenous sphingomyelinase increases transepithelial permeability and decreases transepithelial resistance at concentrations as low as 0.01 U/ml, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
secretory sphingomyelinase is upregulated in chronic heart failure, S-SMase further correlates with reduced skeletal quadriceps muscle strength as well as impaired peripheral vasodilator capacity, physiological function and parameters of S-SMase in heart tissue, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
A-SMase in the outer epidermis is essential for basal permeability function, A-SMase activity in the lower epidermis is involved in basal permeability barrier homeostasis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is important in ceramide metabolism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
SMase C causes hemolysis and thus is suspected to be a potential virulence factor
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
age-related increase in the activity of NSMase-2 is responsible for the interleukin-1beta hyperresponsiveness and a decrease in GSH levels, phenotype, regulation of neutral sphingomyelinase-2 by GSH in oxidative stress in aging-associated inflammation, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, and hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
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
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
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
-
-
?
additional information
?
-
-
exogenous neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
?
additional information
?
-
-
sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion at a step in the fusion process after CD4 engagement, but sphingomyelinase treatment of cells does not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis, and furthermore, sphingomyelinase treatment does not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, Smase treatment does not influence Triton X-100 extraction of HIV-1 receptor proteins, overview
-
-
?
additional information
?
-
-
Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
-
-
?
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
-
-
?
additional information
?
-
-
acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
-
-
?
additional information
?
-
-
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
?
additional information
?
-
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
?
additional information
?
-
-
SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
-
-
?
additional information
?
-
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
?
additional information
?
-
-
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
?
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
-
-
?
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
-
-
?
additional information
?
-
-
acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
-
-
?
additional information
?
-
-
an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
-
-
?
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
?
additional information
?
-
-
Niemann Pick disease is an autosomal recessive disorder due to the deficit of lysosomal acid sphingomyelinase, which results in intracellular accumulation of sphingomyelin. Identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
-
-
?
additional information
?
-
-
nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
-
-
?
additional information
?
-
-
patients with atopic dermatitis show reduced activities of acid and neutral sphingomyelinase. The reduced acid sphingomyelinase activity may be partially responsible for the reduced content of stratum corneum ceramides. Reduced neutral sphingomyelinase activity may lead to changes in signal transduction, thereby regulating differentiation. The resulting reduction in involucrin could cause the reduced number of covalently bound ceramides in atopic dermatitis
-
-
?
additional information
?
-
-
spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
-
-
?
additional information
?
-
-
UV light-triggered ASMase activation is essentially required for bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac
-
-
?
additional information
?
-
-
a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
-
-
?
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
?
additional information
?
-
-
common polymorphisms of the SMPD1 gene occur in Niemann-Pick disease type A and B, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
-
-
?
additional information
?
-
-
exogenous acidic sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
?
additional information
?
-
-
exposure to the NO donors promotes an increase in the protein-protein interaction between acidic sphingomyelinase and caspase-3, with aSMase sequestering caspase-3 and preventing its cleavage and inhibiting apoptosis, overview
-
-
?
additional information
?
-
-
many signaling molecules involved in the pathogenesis of intestinal epithelial barrier, such as TNF-alpha or IFN-gamma, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases
-
-
?
additional information
?
-
-
neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors are essentially involved in endothelial nitric oxide synthase activation by tumor necrosis factor alpha, regulation of the pathway, overview
-
-
?
additional information
?
-
-
neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
-
-
?
additional information
?
-
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, different oxidants modulate different enzymes of the ceramide generating machinery to induce apoptosis in airway epithelial cells, overview
-
-
?
additional information
?
-
-
role for nSMase2 in pro-inflammatory responses induced by TNF-alpha as a regulator of adhesion proteins, both p38-alpha MAPK and nSMase2 are involved in the TNF-alpha-stimulated up-regulation of the adhesion proteins vascular cell adhesion molecule-1 and intercellular adhesion molecule-1
-
-
?
additional information
?
-
-
ASM is necessary for stress-induced cell death
-
-
?
additional information
?
-
-
the specific ligand binding activity of the serotonin1A receptor in membranes isolated from CHO-5-HT1AR cells is increased upon sphingomyelinase treatment (25 or 50 mU/ml) for 90 min in DMEM/F-12 medium under serum free condition
-
-
?
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
-
-
?
additional information
?
-
the enzyme is a virulence factor
-
-
?
additional information
?
-
-
the enzyme is a virulence factor
-
-
?
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
-
-
?
additional information
?
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
?
additional information
?
-
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
?
additional information
?
-
-
modification of the SMase/SM-synthase balance, shown in the nuclei 1 h after serum deprivation, appears specific for the early events of the apoptotic process
-
-
?
additional information
?
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
?
additional information
?
-
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
?
additional information
?
-
-
spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
-
-
?
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
?
additional information
?
-
-
ASMase inhibition decreases ceramide generation during ischemia/reperfusion, and attenuates serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation, overview, the enzyme is involved in hepatic ischemia/reperfusion damage, ceramide generated from ASMase plays a key role in I/R-induced liver damage, molecular mechanisms, overview
-
-
?
additional information
?
-
-
ASMase activity is required for an efficient fusion of late phagosomes with lysosomes including the efficient transfer of lysosomal hydrolases into phagosomes containing Listeria monocytogenes
-
-
?
additional information
?
-
-
Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
-
-
?
additional information
?
-
-
Src kinase-dependent phosphorylation of p38 MAPK is involved in P2X7-induced A-SMase activation, A-SMase mediates ATP receptor P2X7R-dependent microparticle shedding and P2X7-dependent IL-1beta release
-
-
?
additional information
?
-
-
The sphingomyelinase, but not the phospholipase C activity, is essential for induction of hot-cold hemolysis in human erythrocytes, that contain both phosphatidylcholine and sphingomyelin but also in goat erythrocytes, which lack phosphatidylcholine, however, in horse erythrocytes, with a large proportion of phosphatidylcholine and almost no sphingomyelin, hot-cold hemolysis induced by PlcHR2 is not observed, overview. Sphingomyelinase activity gives rise to the formation of ceramide-rich, rigid membrane domains that are resistant to Triton X-100 solubilization
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
?
additional information
?
-
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
-
-
?
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
?
additional information
?
-
-
neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
-
-
?
additional information
?
-
-
a phosphatidylcholine/sphingomyelin metabolism crosstalk which regulates the intranuclear ceramide/diacylglycerol pool exists in the chromatin structure, effect of phosphatidylcholine-specific phospholipase C activity on neutral sphingomyelinase and reverse sphingomyelin synthase, which enrich the intranuclear ceramide pool, overview
-
-
?
additional information
?
-
-
aging in rats causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2, NSMase-2 is both required and sufficient for the onset of IL-1beta hyperresponsiveness during aging, overview
-
-
?
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
?
additional information
?
-
-
neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats and is a key event in glutathione repletion, overview
-
-
?
additional information
?
-
-
the enzyme is involved in sphingomyelin digestion
-
-
?
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
?
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
-
-
?
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(1-aminodecane-1,1-diyl)bis(phosphonic acid)
-
a substrate analogue inhibitor of aSMase
1,2-dioleoyl-sn-glycerol
-
approx. 40% inhibition at 3.2 mM
1,2-distearoyl-rac-glycerol
-
approx. 30% inhibition at 3.2 mM
1,3,5-tri-O-dodecylsulfonyl-D_myo-inositol
-
-
1,3,5-tri-O-ethylsulfonyl-D-myo-inositol
-
-
1,3,5-tri-O-methylsulfonyl-D-myo-inositol
-
-
1,3,5-tri-O-octylsulfonyl-D-myo-inositol
-
-
1-aminodecylidene bis-phosphonic acid
-
1-O-dodecylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-ethylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-hexylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-methylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-octylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-oleoyl-rac-glycerol
-
slight stimulation below 0.8 mM, approx. 50% inhibition at 3.2 mM
1-stearoyl-rac-glycerol
-
slight stimulation below 0.8 mM, approx. 10% inhibition at 3.2 mM
2'-AMP
-
mixture with 3'-AMP
27-Hydroxycholesterol
inhibition of acid sphingomyelinase; inhibition of neutral sphingomyelinase occurs at a posttranscriptional level
3',5'-cAMP
-
IC50: above 0.5 mM
3'-AMP
-
mixture with 2'-AMP
3-acetyl-11-keto-beta-boswellic acid
-
62% inhibition of acid SMase at 0.1 mM
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
3-[benzyl(tert-butyl)amino]-1-(4-nitrophenyl)propan-1-one
-
-
5-adenoylimino phosphate
-
IC50: above 0.5 mM
6-O-dodecylsulfonyl-D-glucose 2,4-bisphosphate
-
-
6-O-ethylsulfonyl-D-glucose 2,4-bisphosphate
-
-
6-O-hexylsulfonyl-D-glucose 2,4-bisphosphate
-
-
6-O-octylsulfonyl-D-glucose 2,4-bisphosphate
-
-
AD2765
-
a substrate analogue inhibitor of aSMase
adenine-9-beta-D-arabinofuranoside 5'-monophosphate
-
-
adeno 5'-diphosphate
-
IC50: above 0.5 mM
adeno-2',3'-cyclic phospho 5'-monophosphate
-
IC50: 0.2 mM
adeno-2',3'-cyclic phospho 5'-phosphosulfate
-
IC50: 0.5 mM
adenosine 3',5'-diphosphate
-
-
adenosine 5'-monophosphate
-
periodate-oxidized and an isomer with arabinose instead of ribose as sugar component
Adenosine 5'-O-thiomonosulfate
-
-
adenosine 5'-phosphosulfate
-
-
alpha-mangostin
-
a xanthone from the bark of Garcinia speciosa
arachidonic acid
-
slight stimulation below 0.8 mM, approx. 50% inhibition at 3.2 mM
BeF2
an unusual phosphate analogue
C11AG
-
inhibits N-SMases in T-cells and macrophages
Cetylpyridinium chloride
-
-
cetyltrimethylammonium bromide
chitosan-iron complex FeChi-CH3
-
-
-
Chloroquine
-
diphosphate salt, 50% inhibition at 5 mM
cholesterol
-
strong inhibition in the presence of 0.4 mM linoleic acid
cis, cis-cyclohexane 1,3,5-trisphosphate
-
barely inhibits aSMase even at a 0.1 mM concentration
cowanin
-
a xanthone from the bark of Garcinia speciosa
cowanol
-
a xanthone from the bark of Garcinia speciosa
curcumin
-
inhibits acid SMase, but not neutral and alkaline SMase, in Caco-2 cells with an antiproliferative effect, the effect is more potent in monolayers than in polarised cells, metabolis effects, overview
ES048
-
when tested in splenocyte extracts, ES048 specifically inhibits enzyme activity up to a concentration of 0.002 mM
gangliosides
-
particularly monogangilosides
-
L-carnitine
-
specific inhibitor
linoleic acid
-
slight stimulation below 0.8 mM, approx. 45% inhibition at 3.2 mM
linolenic acid
-
stimulation below 0.8 mM, approx. 15% inhibition at 3.2 mM
lysophosphatidic acid
-
IC50: 0.04 mM
mannose 6-phosphate
-
Niemann-Pick disease fibroblasts
myo-inositol 1,3,5-trisphosphate
-
-
myo-Inositol 3,5-bisphosphate
-
-
n-butanol
-
plasma membrane
N-tosyl-L-phenylalanyl chloromethyl ketone
-
-
N-[(2S,3R,4E)-1-(2,2'-bipyridin-6-ylmethoxy)-3-hydroxyoctadec-4-en-2-yl]hexanamide [Mg2+]
-
i.e. RY221B-a, synthesis, binding simulations and docking study, overview
N-[(2S,3R,4E)-3-(2,2'-bipyridin-6-ylmethoxy)-1-hydroxyoctadec-4-en-2-yl]hexanamide
-
i.e. RY221B-b, synthesis, binding simulations and docking study, overview
NAD+
-
IC50: above 0.5 mM
NADP+
-
IC50: above 0.5 mM
oleic acid
-
stimulation below 0.8 mM, approx. 10% inhibition at 3.2 mM
p-chloromercuribenzoate
-
plasma membrane and microsomes
p-hydroxymercuribenzoate
-
slight
palmitate
-
a non-substrate lipid belonging to the phospholipase A2 pathway
peroxynitrite
irreversible inhibition of nSMase1
phenylmethylsulfonyl fluoride
70.3% residual activity at 2 mM
phosphatidyl inositol 3,5-bisphosphate
-
potent selective acid sphingomyelinase inhibitor
phosphatidyl inositol-3,5-bisphosphate
-
-
phosphatidyl-myo-inositol 3,4,5-triphosphate
-
IC50: 0.003 mM
phosphatidyl-myo-inositol 4,5-diphosphate
-
IC50: 0.25 mM
phosphatidylcholine
-
IC50: 2 mM
phosphatidylinositol 3,5-bisphosphate
-
potent inhibitor
phosphatidylinositol 4',5'-bisphosphate
-
-
phosphatidylinositol-4,5-bisphosphate
-
-
platelet-activating factor
-
hydrolysis of sphingomyelin
platelet-inactivating factor
-
pronase E
-
reduction of stimulation of the two activator proteins
-
reactive oxygen species
reversible inhibition of nSMase1
-
SDS
67.7% residual activity at 2 mM
sphingosylphosphocholine
-
-
SR33557
-
the calcium channel inhibitor performs indirect inhibition of aSMase
stearic acid
-
slight stimulation below 0.8 mM, approx. 10% inhibition at 3.2 mM
taurocholate
-
in presence of Triton X-100
triolein
-
approx. 30% inhibition at 3.2 mM
tristearin
-
approx. 35% inhibition at 3.2 mM
Trypsin
-
inactivation in pancreas, liver, duodenum but not in intestine, acid sphingomyelinase
-
[(2S)-1,1-difluoro-3-(hexadecanoylamino)-2,4-dihydroxy-4-phenylbutyl]phosphonic acid SMA-3
-
-
[(4S)-1,1-difluoro-3-(hexadecanoylamino)-4-hydroxy-4-phenylbutyl]phosphonic acid
-
-
3-O-methylsphingomyelin
-
-
3-O-methylsphingomyelin
-
-
3-O-methylsphingomyelin
-
-
3-O-methylsphingomyelin
-
-
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
-
-
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
-
inhibits taurocholate-induced activation
5'-AMP
-
-
amitriptyline
-
-
amitriptyline
-
performs indirect inhibition of aSMase
amitriptyline
-
specific inhibitor
amlodipine
-
-
AMP
-
-
AMP
-
IC50: 0.08 mM, non-competitive inhibition
astemizole
-
-
benztropine
-
-
bepridil
-
-
Ca2+
-
when sphingomyelin as substrate with Triton X-100 is used, competitive inhibitor against Mg2+
Ca2+
-
completely inhibited at 5 mM CaCl2
Ca2+
-
6.9 mM, 50% inhibitiion
Ca2+
-
0.1 mM, 60% inhibition of Mg2+-activated N-SMase
Ca2+
inhibits the hemolytic enzyme activity
Ca2+
-
strong inhibition of hemolysis at 10 mM
camylofin
-
-
ceramide
-
feedback inhibition
ceramide
product feedback inhibition; product feedback inhibition
ceramide
-
23% inhibition
ceramide
-
strong inhibition in the presence of 0.4 mM linoleic acid
cetyltrimethylammonium bromide
-
-
cetyltrimethylammonium bromide
-
-
CHAPS
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
CHAPS
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
CHAPS
-
hydrolysis of sphingomyelin and platelet-activating factor
CHAPS
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
chlorprothixene
-
-
clomiphene
-
-
cloperastine
-
-
Cu2+
-
0.0079 mM, 50% inhibitiion
Cu2+
-
5 mM, complete inhibition
cyclobenzaprine
-
-
cyproheptadine
-
-
D609
-
nonspecific sphingomyelinase inhibitor
D609
-
48% inhibition of the enzyme in chromain after 30 min of treatment, no inhibition by D609 in the nuclear membrane
deoxycholate
inhibits almost 90% of the activity at 3 mM
desipramine
-
desipramine
-
inhibits acidic SMase
desipramine
-
inhibits the acid SMase, and lipopolysaccharide induction of interleukin-8 synthesis in vivo
desipramine
-
performs indirect inhibition of aSMase
desipramine
-
inhibits the processed lysosomal L-SMase
desipramine
-
specific inhibitor
dithiothreitol
-
-
dithiothreitol
-
10 mM, 25% inhibition
dithiothreitol
33.1% residual activity at 2 mM
doxepine
-
-
drofenine
-
-
EDTA
-
-
EDTA
-
complete inhibition at 0.25 mM
EDTA
-
10 mM, 95% inhibition
EDTA
-
20 mM, complete inhibition
EDTA
5 mM, complete inhibition, activity is comletely restored by the subsequent addition of 10 mM Mg2+ or Mn2+
EDTA
-
alk-SMase activity with platelet-inactivating factor
EDTA
significant inhibition at 5 mM
EDTA
-
5 mM, complete inhibition, subsequent addition of Mn2+, Mg2+ or Ca2+ restores activity to 300% of that before EDTA treatment
EDTA
-
alk-SMase activity with platelet-inactivating factor; inhibits hydrolysis of platelet-activating factor, no effect on hydrolysis of sphingomyelin
EDTA
complete inhibition at 2 mM
Fe3+
-
-
fendiline
-
-
fluoxetine
-
-
glutathione
-
-
glutathione
-
0.2 mM, almost complete inhibition
glutathione
-
then oxidized
glutathione
-
3 mM, 95% inhibition
GSH
-
inhibition of all T-mSMase and S-mSMase isoforms above 2.5 mM
GSH
-
a potent inhibitor of liver NSMase-2 activity
GW4869
-
inhibited by 0.001-0.1 mM
GW4869
specific inhibition
GW4869
-
inhibits the neutral SMase, and lipopolysaccharide induction of interleukin-8 synthesis in vivo
GW4869
0.015 mM, 40% inhibition, 0.045 mM, 70% inhibition
Hg2+
-
-
Hg2+
-
5 mM, complete inhibition
Hg2+
-
plasma membrane and microsomes
imipramine
-
-
imipramine
-
performs indirect inhibition of aSMase
imipramine
-
specific inhibitor
imipramine
-
ASMase inhibitor
maprotiline
-
-
Mg2+
-
lysosomal enzyme, inhibition at below pH 4.8
Mg2+
-
slight inhibitory at higher concentrations
Mn2+
-
above 0.5 mM
Mn2+
slight inhibition above 2 mM
Ni2+
-
-
Ni2+
-
5 mM, complete inhibition
norfluoxetine
-
-
nortriptyline
-
-
oxidized glutathione
reversible inhibition of nSMase1
paroxetine
-
-
phosphate
-
-
phosphate
-
IC50: 10 mM, non-competitive inhibition
phosphatidylinositol
-
-
phosphorylcholine
-
-
phosphorylcholine
-
23% inhibition
pimethixene
-
-
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
promazine
-
-
Promethazine
-
-
protriptyline
-
-
scyphostatin
-
0.02 mM, complete inhibition
scyphostatin
-
isolated from Discomycetes, specifically inhibits N-SMases
scyphostatin
-
specific inhibitor of nSMase
scyphostatin
-
isolated from Discomycetes, specifically inhibits N-SMases
scyphostatin
-
isolated from Discomycetes, specifically inhibits N-SMases
scyphostatin
-
0.005 mM, 50% inhibition, complete inhibition at 0.033 mM
scyphostatin
-
specific inhibitor of neutral sphingomyelinase, prevents mechanoactivation of neutral sphingomyelinase
scyphostatin
-
isolated from Discomycetes, specifically inhibits N-SMases
scyphostatin
-
inhibition of NSMase activity in hepatocytes from aged rats using leads to reversion to the young phenotype of IL-1beta response
sertraline
-
-
sphingomyelin
-
strong competitive inhibition of platelet-inactivating factor hydrolysis
sphingomyelin
-
hydrolysis of platelet-activating factor; strong competitive inhibition of platelet-inactivating factor hydrolysis
sphingosine
-
-
suloctidil
-
-
terfenadine
-
-
triflupromazine
-
-
Triton X-100
-
slight inhibition with 2-hexadecynoylamino-4-nitrophenylphosphorylcholine
Triton X-100
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
Triton X-100
-
strong inhibition in the presence of 0.05-0.2% Triton X-100
Triton X-100
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
Triton X-100
inhibits almost 90% of the activity at 0.1%
Triton X-100
-
dose dependent, alkaline sphingomyelinase
Triton X-100
-
hydrolysis of sphingomyelin and platelet-activating factor
Triton X-100
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
Zn2+
-
0.0042 mM, 50% inhibitiion, higher concentrations of Mg2+ slighty restore activity
Zn2+
-
the enzyme possesses at least two different binding sites for Zn2+. Zn2+ binding to the high affinity site can activate the enzyme, whereas the Zn2+ binding to the low-affinity site can activate the enzyme. Binding of the substrate to the enzyme is independent of the Zn2+ binding to the high-affinity site, but is competitively inhibited by the Zn2+ binding to the low-affinity site. Rank-order of increasing activation: Mg2+, Co2+, Mn2+, Zn2+. The four metal ions compete with each other for the same binding site on the enzyme molecule
Zn2+
Zn2+ binding to the high-affinity site activates the enzyme and, conversely, binding to the low-affinity site inhibits the enzyme
Zn2+
-
almost complete inhibition of Mg2+-activated N-SMase
Zn2+
-
nSMase activity of the recombinant protein nSM1 abolishes (12% residual activity) by 5 mM Zn2+
Zn2+
-
required for activity, best at 0.5-1 mM, inhibitory above 10 mM
Zn2+
high millimolar Zn2+ concentration leads to inhibition of enzyme activity
Zn2+
complete inhibition at 0.1 mM
Zn2+
-
required for activity, best at 0.5-1 mM, inhibitory above 10 mM
Zn2+
-
5 mM, complete inhibition
Zn2+
-
0.1-0.25 mM inhibits hydrolysis of platelet-activating factor, concentrations above 0.25 mM inhibit hydrolysis of sphingomyelin and platelet-activating factor
additional information
-
neuraminidase from Clostridium perfringens inhibits the binding of the enzyme to mouse peritoneal macrophages
-
additional information
-
not inhibited by GW4869
-
additional information
-
activity is inhibited by plant extracts of Abies nephrolepis, Acer tegmentosum and Ginkgo biloba with the inhibition constant of 0.0119 mg/ml, 0.0094 mg/ml and 0.0129 mg/ml, respectively
-
additional information
-
not inhibited by fumonisin B1
-
additional information
-
no effect on activity by monosialic ganglioside GM3 and phospholipids
-
additional information
-
EDTA or EGTA in the reaction mixture have no effect on the basal activity
-
additional information
-
-
-
additional information
-
in polarized cells, ursodeoxycholic acid has no effect in acid and neutral sphingomyelinase. In monolayer cell ursodeoxycholic acid reduces both acid and neutral sphingomyelinase activities
-
additional information
-
the tricyclic antidepressant desipramine possibly induces intracellular proteolysis of A-SMase by displacing the enzyme from its membrane-bound lipid substrate and thereby making it sensitive to proteolysis. The resulting loss of lysosomal A-SMase activity may well trigger the lysosomal lipid accumulation
-
additional information
-
protein kinase C-delta inhibits the activation of N-SMase by 1,25-dihydroxyvitamin D3
-
additional information
-
Alk-SMase is resistant to trypsin digestion
-
additional information
-
ASM detachment from lysosomal membranes, caused by weak bases inhibit the enzyme, usage of structure-property-activity relation model in inhibitor screening, overview, no inhibition of ASM by dicyclomine, diphenhydramine, diphenylpyraline, donepezil, lercanidipine, mebeverine, memantine, oxymetazoline, oxyphencyclimine, pyrilamine, triprolidine, and xylometazoline
-
additional information
-
desipramine is a cationic amphiphile that triggers ASM proteolysis
-
additional information
-
prolonged treatment with adriamycin by 24 h and beyond causes a down-regulation in nSMase3 expression, activation of p53 also down-regulates nSMase3 expression
-
additional information
-
3-acetyl-11-keto-beta-boswellic acid does not inhibit neutral or alkaline SMase activity
-
additional information
-
Alk-SMase is resistant to trypsin digestion
-
additional information
-
pentoxifylline treatment preventsTNFupregulation and ASMase activation
-
additional information
-
Salmonella enterica serovar typhimurium infection reduces ASM activity, overview
-
additional information
-
no inhibitory effect is observed in cultures treated with inhibitors of neutral SMase such as manumicyn (0.001 mM) or GW4869 (0.005 mM)
-
additional information
oxidizing agents inhibit enzyme activity in a dose-dependent manner that correlates with hyperaggregation of the enzyme protein, which can be restored by immediate addition of DTT
-
additional information
-
oxidizing agents inhibit enzyme activity in a dose-dependent manner that correlates with hyperaggregation of the enzyme protein, which can be restored by immediate addition of DTT
-
additional information
-
ceramidase inhibits hot-cold hemolysis induced by PlcHRx2, Cer is essential in the mechanism of hot-cold hemolysis
-
additional information
-
-
-
additional information
-
bile diversion reduces the alkaline SMase activity by 85% in the small intestinal content and 68% in the faeces, but not in the intestinal mucosa
-
additional information
-
Alk-SMase is resistant to trypsin digestion
-
additional information
-
ASM detachment from lysosomal membranes caused by weak bases inhibit the enzyme, usage of structure-property-activity relation model in inhibitor screening, overview, no inhibition of ASM by dicyclomine, diphenhydramine, diphenylpyraline, donepezil, lercanidipine, mebeverine, memantine, oxymetazoline, oxyphencyclimine, pyrilamine, triprolidine, and xylometazoline
-
additional information
the enzyme is not inhibited by mercaptoethanol and iodoacetamide
-
additional information
-
the enzyme is not inhibited by mercaptoethanol and iodoacetamide
-
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1-alpha,25-dihydroxyvitamin D3
-
-
1-oleoyl-rac-glycerol
-
approx. 20% stimulation at 0.4-0.8 mM, inhibition above
1-stearoyl-rac-glycerol
-
approx. 10% stimulation at 0.8 mM, inhibition above
Activator proteins
-
from human spleen, two forms of
-
albumin
-
20% activation of enzyme A and B
-
anionic phospholipids
-
APLs, the enzymatic activity of nSMase2 is dependent on anionic phospholipids, structural requirements for APL-selective binding of nSMase2, overview. nSMase2 interacts specifically and directly with several APLs, including phosphatidylserine and phosphatidic acid. Identification of two discrete APL binding domains in the N terminus of nSMase2, the nSMase2 N-terminal domain is essential for nSMase interaction with APLs
-
Bile salts
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
C2 toxin
-
activates acid but not neutral sphingomyelinase
-
cetyltrimethylammonium bromide
-
low concentrations
choline
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
dioleoyl-phosphatidylserine
0.05 mM, 4fold activation
DTT
activates in vivo by severalfold
Fas ligand
-
activates sphingomyelinases, expecially acid SMase
-
galectin-I
-
human, induces apoptosis and initiates the acid SMase-mediated release of ceramide
-
glutathione
activates in vivo by severalfold
H2O2
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, overview
linoleic acid
-
approx. 20% stimulation at 0.8 mM, inhibition above
linolenic acid
-
approx. 30% stimulation at 0.8-1.6 mM, inhibition above
Lipids
-
saturated and unsaturated fatty acids
-
lyso-phosphatidylcholine
-
-
oleic acid
-
approx. 40% stimulation at 0.8 mM, inhibition above
ONOO-
-
peroxynitrite specifically activates the acidic sphingomyelinase
phorbol 12-myristate 13-acetate/protein kinase Cdelta
-
activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation, which is mediated by phorbol 12-myristate 13-acetate, that induces also membrane translocation of ASMase, formation of a novel PKCdelta-ASMase complex after PMA stimulation, mechanism, overview
-
phosphatidylcholine
-
0.2 mM, 2fold activation
phosphatidylcholine-specific phospholipase C
-
increases the N-SMase activity up to 2fold
-
phosphatidylethanol
0.05 mM, 2fold activation
protein kinase C-zeta
-
mediates the activation of N-SMase by 1,25-dihydroxyvitamin D3, while protein kinase C-delta inhibits the activation
-
reduced glutathione
-
activation in a dose dependent manner
salts
-
trihydroxy- and dihydroxy-bile salt
-
saposin C
-
presence of sphingolipid activator proteins, e. g. saponsins, is not essential for activity. Saposin C increases activity of the P153A mutant enzyme, but does not result in complete restoration of the activity
-
sodium cholate
129% relative activity at 6% (v/v) sodium cholate
sphingomyelin
-
dietary sphingomyelin increases the alk-Smase activity in the colon by 65%, the increased activity is associated with increased protein and mRNA expression
stearic acid
-
approx. 20% stimulation at 0.4-0.8 mM, inhibition above
taurodeoxycholate
-
the enzyme activity is specifically stimulated by about 2.5 mM taurodeoxycholate
TNF-alpha
-
increases N-SMase activity rapidly and transiently both endogenously and in cells overexpressing nSMase2, and induces membrane translocation of nSMase2, regulated by p38-alpha MAPK, the increase in endogenous N-SMase activity is abrogated by p38 MAPK inhibition
-
tumor necrosis factor-alpha
-
2-mercaptoethanol
-
-
2-mercaptoethanol
activates in vivo by severalfold
arachidonic acid
-
approx. 3fold activation at 0.5 mM
arachidonic acid
-
approx. 3fold activation at 0.5 mM
arachidonic acid
-
approx. 20% stimulation at 0.4-0.8 mM, inhibition above
bile salt
-
dependent on, particularly taurocholate and taurochenodeoxycholate
bile salt
-
required for activity
bile salt
-
dependent on, particularly taurocholate and taurochenodeoxycholate
cardiolipin
0.1 mM, approx. 40fold activation
cardiolipin
enzymatic activity is induced 23fold at 0.1 mM
cardiolipin
-
anionic phospholipids required for activity, maximal activation at 1 mM, 21% of activation with phosphatidylserine
cholate
-
-
cholesterol
-
sphingomyelinase activity is higher in the cholesterol-induced liquid-ordered phase than in the gel phase
cholesterol
-
sphingomyelinase is enhanced by cholesterol and by lipids with an intrinsic negative curvature, e.g. phosphatidylethanolamine
Cutsum
-
-
-
deoxycholate
-
3fold stimulation at concentrations above 0.1%
Detergents
-
-
dithiothreitol
-
dithiothreitol
-
activation in a dose dependent manner
dithiothreitol
required for full activity
dithiothreitol
-
2fold enhanced activity at 3 mM
dithiothreitol
-
approx. 10fold activation at 3-4 mM
EGTA
stimulates activity at low concentrations
EGTA
-
Cu2+ not inhibitory when EGTA added prior
phosphatidic acid
-
-
phosphatidic acid
-
anionic phospholipids required for activity, maximal activation at 1 mM, 33% of activation with phosphatidylserine
phosphatidylethanolamine
-
0.2 mM, 2.9fold activation
phosphatidylethanolamine
-
sphingomyelinase is enhanced by cholesterol and by lipids with an intrinsic negative curvature, e.g. phosphatidylethanolamine
phosphatidylethanolamine
-
-
phosphatidylglycerol
activates nSMase2
phosphatidylglycerol
enzymatic activity is induced 8fold at 0.1 mM
phosphatidylglycerol
-
anionic phospholipids required for activity, maximal activation at 1 mM, 79% of activation with phosphatidylserine
phosphatidylinositol
-
-
phosphatidylinositol
-
anionic phospholipids required for activity, maximal activation at 1 mM, 53% of activation with phosphatidylserine
phosphatidylserine
-
-
phosphatidylserine
-
0.2 mM, 3.8fold activation
phosphatidylserine
enhances activity
phosphatidylserine
0.05 mM, 4fold activation
phosphatidylserine
-
0.2 mM, approx. 108fold activation of sphingomyelin hydrolysis in the presence of 0.1% Triton X-100
phosphatidylserine
activates nSMase2
phosphatidylserine
0.1-0.15 mM, approx. 40fold activation
phosphatidylserine
enzymatic activity is induced 15fold at 0.1 mM
phosphatidylserine
-
anionic phospholipids required for activity, maximal activation at 1 mM
phosphatidylserine
-
required for activity
sodium deoxycholate
-
-
sodium deoxycholate
-
4.4fold activation of S-mSMase epsilon at 2 mM, 4.7fold activation of S-mSMase zeta at 1 mM
staurosporine
-
activates neutral spingomyelinase in a multiphasic manner
staurosporine
-
activates neutral spingomyelinase in a multiphasic manner
taurochenodeoxycholate
-
-
taurochenodeoxycholate
-
-
taurochenodeoxycholate
-
strong activation, maximal activation at approx. 2 mM
taurochenodeoxycholate
-
stimulates hydrolysis of sphingomyelin and platelet-activating factor
taurocholate
-
-
taurocholate
-
the enzyme activity is specifically stimulated by 6 mM taurocholate
taurocholate
-
strong activation, maximal activation at approx. 10 mM
taurocholate
-
stimulates hydrolysis of sphingomyelin and platelet-activating factor
taurocholate
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
TNFalpha
-
S-SMase cytokine TNFalpha activation, completely abrogated by desipramine, overview
-
TNFalpha
-
activates the enzyme, which is prevented by pentoxifylline
-
Triton X-100
-
activation with sphingomyelin
Triton X-100
-
stimulates up to 15fold
Triton X-100
-
0.02%, approx. 3fold activation of T-mSMase gamma
Triton X-100
-
activation of enzyme A and B
Triton X-100
-
0.1%, approx. 108fold activation of sphingomyelin hydrolysis in the presence of 0.2 mM phosphatidylserine
Triton X-100
-
0.1%, approx. 61fold activation of sphingomyelin hydrolysis in the presence of 0.2 mM phosphatidylserine
Triton X-100
required for activity, maximal activation at 0.1%
Triton X-100
-
required for full activity
Triton X-100
required for full activity
Triton X-100
-
activation at very low concentrations
Triton X-100
205% relative activity at 0.1% (v/v) Triton X-100
tumor necrosis factor
-
induces N-SMase activity
-
tumor necrosis factor
-
there is a significant increase in ASMase activity after treatment of MVEC cells with tmor necrosis factor
-
tumor necrosis factor-alpha
-
activates neutral spingomyelinase in a multiphasic manner
-
tumor necrosis factor-alpha
-
activates neutral spingomyelinase in a multiphasic manner
-
additional information
-
the topography of the lipid monolayer surface, through phase connection-disconnection of substrate-enriched or substrate-depleted domains, can dynamically regulate SMase activity
-
additional information
-
no effect on activity by monosialic ganglioside GM3 and phospholipids
-
additional information
heat shock induces Mg2+-dependent neutral SMase activity in ZE cells as early as 1 h after exposure and reaches a peak of activity 2 h after heat shock
-
additional information
-
heat shock induces Mg2+-dependent neutral SMase activity in ZE cells as early as 1 h after exposure and reaches a peak of activity 2 h after heat shock
-
additional information
-
-
-
additional information
-
purified rhASM can be activated in vitro by loss of the free thiol on the C-terminal cysteine via chemical modification, dimerization, or deletion of this amino acid residue
-
additional information
tumor necrosis factor stimulates rapid activation of nSMase3 in MCF7 cells with peak activity at 1.5 min
-
additional information
-
tumor necrosis factor stimulates rapid activation of nSMase3 in MCF7 cells with peak activity at 1.5 min
-
additional information
-
1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine induces neutral sphingomyelinase activity
-
additional information
-
a transient decrease of the GSH/GSSG ratio temporarily activates nSMase-1, while diminishing total glutathione without altering signficantly the GSH/GSSG ratio does not affect nSMase-1 activity, permanent decreases of total glutathione and GSH/GSSG redox ratio produce a sustained activation of nSMase-1 activity, overview
-
additional information
-
activation of acid sphingomyelinase by gemcitabine or doxorubicin, respectively, via reactive oxygen species
-
additional information
nSMase1 activity required reducing agents
-
additional information
nSMase1 activity required reducing agents
-
additional information
nSMase2 is activated by anionic phospholipids
-
additional information
nSMase2 is activated by anionic phospholipids
-
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
-
additional information
-
secretory sphingomyelinase is upregulated in chronic heart failure
-
additional information
-
adriamycin up-regulates endogenous nSMase3 expression within 2 h that last beyond 24 h and declines to control levels by 36 h, tumor necrosis factor-alpha up-regulates endogenous nSMase3 expression within 30 min and declines to control levels by 120 min
-
additional information
-
phorbol 12-myristate 13-acetate does not increase in vitro N-SMase activity protein kinase C-delta does not regulate tumor necrosis factor-induced N-SMase activity
-
additional information
bile salts like taurocholate do not directly stimulate catalysis by the enzyme
-
additional information
-
bile salts like taurocholate do not directly stimulate catalysis by the enzyme
-
additional information
the enzyme with a a built-in N-terminal saposin domain does not require an external saposin activator protein
-
additional information
-
the enzyme with a a built-in N-terminal saposin domain does not require an external saposin activator protein
-
additional information
phospholipids like cardiolipin, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine do not stimulate enzyme activity
-
additional information
-
phospholipids like cardiolipin, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine do not stimulate enzyme activity
-
additional information
-
feeding psyllium, a water-soluble fiber, increases Alk-SMase and decreases N-CDase activity, and thus might enhance ceramide levels in the intestinal mucosa
-
additional information
phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol have minimal effects on MA-nSMase activity
-
additional information
-
phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol have minimal effects on MA-nSMase activity
-
additional information
the enzyme requires a hydrophobic environment for activity
-
additional information
-
the enzyme requires a hydrophobic environment for activity
-
additional information
-
age-related increase in the activity of NSMase-2, attenuated by calorie restriction, aging and interleukin-1beta stimulate NSMase-2 by different mechanisms, overview
-
additional information
-
aging causes increased basal NSMase-2 activity in hepatocytes, which in turn leads to IRAK-1 stabilization, JNK potentiation, and ultimately IL-1beta hyperresponsiveness
-
additional information
not affected by 6% sodium taurocholate and 6% sodium deoxycholate
-
additional information
-
not affected by 6% sodium taurocholate and 6% sodium deoxycholate
-
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evolution
the enzyme belongs to the DNase I superfamily, which contains the exo-endo-phosphatase domain, the domain lacks only in isozyme Sph4, all isozymes lack the beta-hairpin loop, the organism encodes genes Sph1, Sph2, Sph3, Sph4 and SphH, structure comparisons, overview
evolution
the enzyme from Streptomyces seems to be a typical bacterial SMase with a primary structure unusual for known bacterial SMases, primary structure comparisons and phylogenetic analysis
evolution
the enzyme is a member of the metallophosphoesterase enzyme family
evolution
-
the enzyme belongs to the DNase I superfamily, which contains the exo-endo-phosphatase domain, the domain lacks only in isozyme Sph4, all isozymes lack the beta-hairpin loop, the organism encodes genes Sph1, Sph2, Sph3, Sph4 and SphH, structure comparisons, overview
-
evolution
-
the enzyme from Streptomyces seems to be a typical bacterial SMase with a primary structure unusual for known bacterial SMases, primary structure comparisons and phylogenetic analysis
-
malfunction
-
acid SMase-deficient mice show reduced pulmonary ceramide levels and attenuated leukocyte influx into the alveolar space
malfunction
-
an inborn deficiency in aSMase activity leads to a lysosomal storage of sphingomyelin and a fatal pathology that has been designated as the type A and type B of Niemann-Pick-disease
malfunction
-
deficiency of the enzyme leads to lysosomal accumulation of sphingomyelin resulting in in Niemann-Pick types A and B diseases
malfunction
-
glucose intolerance in ASM-/- mice
malfunction
-
loss of nSMase activity leads to a Big-Eye-like phenotype, and affect s protein trafficking, as well as VSG trafficking, overview
malfunction
-
treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
malfunction
-
acid sphingomelin-specific drugs and multiple small interfering RNAs strongly inhibit the infection by ebolavirus and ebolavirus glycoprotein pseudotyped viruses but not by the pseudotypes bearing the glycoprotein of vesicular stomatitis virus, overview. ASMase siRNA-treated cells resist EBOV infection
malfunction
-
decreasing ceramide levels by inhibiting ceramide synthase or neutral sphingomyelinase 2 leads to translocation of membrane-bound aPKC to the cytosol, concurrent with its activation and the phosphorylation of its substrate Aurora kinase A. Ceramide depletion leads to translocation of aPKC from the primary cilium and the apicolateral cell membrane to the cytosol
malfunction
mediates a variety of stress-related cellular processes. The pathological effects of dysregulated acid sphingomyelinase activity are evident in several human diseases and indicate an important functional role for acid sphingomyelinase regulation. Alternative splicing of acid sphingomyelinase is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular enzyme activity
malfunction
Niemann-Pick disease types A and B are autosomal recessive lysosomal storage disorders caused by acid sphingomyelinase deficiency due to mutation in the sphingomyelin phosphodiesterase 1 gene, clinical manifestations, overview
malfunction
-
acid sphingomyelinase inhibition causes cellular sphingomyelin accumulation, which induces cancer cell death specifically in hypoxic tumor spheroids
malfunction
-
enzyme inhibition blocks T-helper cell responses. Enzyme knockdown dampens CD3/CD28 signals and broadly inhibits T-helper cell responses
malfunction
-
enzyme ablation reduces cell polarity
malfunction
-
enzyme knockdown reduces Clostridium botulinum C2 toxin-induced cell rounding
malfunction
inactivating enzyme mutations cause Niemann-Pick disease
malfunction
-
treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
-
malfunction
-
glucose intolerance in ASM-/- mice
-
metabolism
-
all-trans-retinoic acid induction of nSMase2 stimulates an increase in ceramide levels followed by G0/G1 growth arrestin MCF-7 cells. nSMase2 siRNA significantly inhibits all-trans-retinoic acid effects on ceramide levels and growth arrest. Neither all-trans-retinoic acid stimulation nor nSMase2 overexpression have significant effects on classical cell cycle regulators such as p21/WAF1 or retinoblastoma. In contrast, all-trans-retinoic acid suppresses phosphorylation of ribosomal S6 kinase and its downstream targets S6 and eIF4B, which is significantly inhibited by nSMase2 siRNA. nSMase2 overexpression is sufficient to suppress S6K phosphorylation and signaling
metabolism
-
ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. Loss of sphingosine kinase-1 diminishes ASM-mediated AKT phosphorylation, but exogenous S1P induces AKT activation in hepatocytes. In contrast, SphK1 deficiency does not affect AMPK activation. The SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation
metabolism
-
ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. Loss of sphingosine kinase-1 diminishes ASM-mediated AKT phosphorylation, but exogenous S1P induces AKT activation in hepatocytes. In contrast, SphK1 deficiency does not affect AMPK activation. The SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation
metabolism
-
interaction in the NO/NOS and SMases/ceramide signaling pathways, overview
metabolism
-
the essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei
metabolism
-
key enzyme in sphingolipid metabolism
metabolism
-
key enzyme in sphingolipid metabolism
metabolism
-
ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. Loss of sphingosine kinase-1 diminishes ASM-mediated AKT phosphorylation, but exogenous S1P induces AKT activation in hepatocytes. In contrast, SphK1 deficiency does not affect AMPK activation. The SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation
-
metabolism
-
ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. Loss of sphingosine kinase-1 diminishes ASM-mediated AKT phosphorylation, but exogenous S1P induces AKT activation in hepatocytes. In contrast, SphK1 deficiency does not affect AMPK activation. The SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation
-
physiological function
-
in HepG2 cells SMase treatment significantly enhances the esterification of cholesterol by a 50% with respect to control cells
physiological function
-
acid sphingomyelinase catalyzes the cleavage of sphingomyelin to generate ceramide. Ceramide levels may be a determining factor in osteoclast formation. As ceramide levels are also regulated by sphingosine kinase, as well as ASM. ASM differentially regulates sphingosine kinase 1 and sphingosine kinase 2 expression, the sphingosine kinases show opposing effects on osteoclast formation
physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
physiological function
-
all-trans-retinoic acid regulation of nSMase2, overview
physiological function
-
alpha-toxin, a major determinant of Clostridium perfringens toxicity, exhibits both phospholipase C and sphingomyelinase activities with distinct, but partially overlapping and interacting active sites
physiological function
-
APLs, the enzymatic activity of nSMase2 is dependent on anionic phospholipids, structural requirements for APL-selective binding of nSMase2, overview. nSMase2 interacts specifically and directly with several APLs, including phosphatidylserine and phosphatidic acid. Identification of two discrete APL binding domains in the N terminus of nSMase2, the nSMase2 N-terminal domain is essential for nSMase interaction with APLs. APL binding domains are important for nSMase2 to localize at the plasma membrane
physiological function
-
aSMase is known to induce apoptosis in a variety of cell lines and is emerging as an important mediator of inflammation in various pathological backgrounds
physiological function
-
role for A-SMase in the release of plasma membrane-derived microparticles, overview A-SMase is a cation-independent hydrolase contributing to the catabolism of sphingomyelin in lysosomes. Stress is believed to activate A-SMase to generate ceramide, which serves as a cellular mediator in initiating apoptotic response, the process is controlled by NO, detailed overview. A-SMase activity is also crucial for developmental programmed cell death of oocytes. Modeling of A-SMase function in apoptosis, overview
physiological function
-
the enzyme controls hydrolysis of surface membrane sphingomyelin molecules, thus allowing nutrients, but not host antibodies, to access proteins at the host-parasite interface
physiological function
-
the enzyme controls hydrolysis of surface membrane sphingomyelin molecules, thus allowing nutrients, but not host antibodies, to access proteins at the host-parasite interface
physiological function
-
the neutral sphingomyelinase is essential for growth and survival of the parasite. The formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface
physiological function
-
as a key enzyme in sphingolipid metabolism, acid sphingomyelinase is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. Increased activity of the lysosomal form is associated with various pathological conditions
physiological function
-
as a key enzyme in sphingolipid metabolism, acid sphingomyelinase is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. Increased activity of the lysosomal form is associated with various pathological conditions, the extracellular enzyme from cerebrospinal fluid migh also play a role in human disease
physiological function
critical role(s) of sphingomyelinase and ceramidase during pregnancy and lactation and their downstream effects on adult progeny fitness. The mother provides her offspring with nutrients required for development solely via intrauterine lactation
physiological function
critical role(s) of sphingomyelinase and ceramidase during pregnancy and lactation and their downstream effects on adult progeny fitness. The mother provides her offspring with nutrients required for development solely via intrauterine lactation. aSMase1 is regulated and expressed in a pregnancy and milk gland-specific manner
physiological function
-
neural differentiation of human embryonic stem cells to neuroprogenitors is concurrent with a threefold elevation of ceramide, in particular, saturated, long-chain C16:0 ceramide (N-palmitoyl sphingosine) and nonsaturated, very long chain C24:1 ceramide (N-nervonoyl sphingosine), involving the enzyme activity, critical role of ceramide generated by nSMase2 in stem cell ciliogenesis and differentiation
physiological function
neutral sphingomyelinase-2 is the major sphingomyelinase activated in response to proinflammatory cytokines and during oxidative stress. The enzyme may be a novel substrate for thioredoxin
physiological function
-
rhinovirus and measles virus each require the enzyme activity during early stages of infection, as well as the ebolavirus. Both sphingomyelin and ceramide are important components of lipid rafts and are potent signaling molecules. Each plays roles in mediating macropinocytosis, which has been shown to be important for ebolavirus infection. The binding of virus-like particles to cells is strongly associated with surface-localized ASMase as well as sphingomyelin-enriched sites, overview
physiological function
-
role for the enzyme in the acceleration of the production of TNF-induced interleukin-6 as a pro-inflammatory cytokine, electrophiles can potentiate inflammation response by up-regulating of ASMase expression following formation of lipid rafts. Expression of ASMase facilitates the clustering of TNFR1 in the lipid raft that in turn enhanced the sensibility of TNF-alpha for the production of interleukin-6
physiological function
-
the dimeric enzyme is an important virulence factor in model Pseudomonas aeruginosa infections and is selectively cytotoxic, at picomolar concentrations to mammalian endothelial cells
physiological function
-
the enzyme is a regulator of mast cell function, detailed overview. Degranulation of mast cells is stimulated by store-operated Ca2+-entry, while in other cell types, Ca2+-entry is modified by ceramide. Exogenously added ceramide has been shown to trigger mast cell apoptosis. Ceramide is produced from sphingomyelin by acid sphingomyelinase. Decrease in body temperature upon the induction of systemic anaphylaxis is significantly less pronounced in asm-/- mice than in asm+/+ mice
physiological function
-
the enzyme is a virulence factor for septicemia. Ganglioside GM3 is the primary cellular receptor for the enzyme, and the beta-hairpin region is the tethering region for gangliosides
physiological function
the recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
physiological function
-
Clostridium botulinum C2 toxin requires acid sphingomyelinase activity during internalization into cells
physiological function
-
neutral sphingomyelinase 2 is required for cytokine-induced skeletal muscle calpain activation. Enzyme activation is required for the development of infection-induced diaphragm calpain activation and muscle weakness
physiological function
-
the enzyme activity is important in T cell recruitment and directional migration. The enzyme is highly important in directional T cell motility in response to SDF1-alpha
physiological function
the enzyme acts as a negative regulator of innate immune signaling, affecting cellular lipid composition and membrane fluidity
physiological function
-
the enzyme mediates T-cell proliferation after anti-CD3/CD28 antibody stimulation and alters CD4+ T-cell activation signals by generating ceramide
physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
-
physiological function
-
the recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
-
physiological function
-
the enzyme is a virulence factor for septicemia. Ganglioside GM3 is the primary cellular receptor for the enzyme, and the beta-hairpin region is the tethering region for gangliosides
-
physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
-
physiological function
-
alpha-toxin, a major determinant of Clostridium perfringens toxicity, exhibits both phospholipase C and sphingomyelinase activities with distinct, but partially overlapping and interacting active sites
-
additional information
-
aSMase exists in two forms: a Zn2+-independent lysosomal aSMase, L-SMase, and a Zn2+-dependent secreted aSMase, S-SMase, that arise from alternative trafficking of a single protein precursor. Mechanism of aSMase maturation involving C-terminal proteolytic processing within, or in close proximity to, endolysosomes, overview
additional information
-
besides the aSMase, an alkaline sphingomyelinase and two neutral sphingomyelinases 1 and 2, nSMase1 and nSMase2, exist
additional information
-
comparison of in vivo activity of nSMase in Schistosoma mansoni with the activity in Schistosoma haematobium, overview
additional information
-
comparison of in vivo activity of nSMase in Schistosoma mansoni with the activity in Schistosoma haematobium, overview
additional information
-
establishing enzyme activity in lipid vesicles, method development, overview. Both lipase activities are sensitive to vesicle size, but in opposite ways: while phospholipase C is higher with larger vesicles, sphingomyelinase activity is lower
additional information
-
from the gene of A-SMase, another product may be generated, i.e., the secretory SMase, which is very similar to A-SMase, differing only in the intracellular trafficking and in the need of zinc for activation
additional information
a redox sensitive enzyme
additional information
-
a redox sensitive enzyme
additional information
homology model of aSMase enzyme with consensus motif NX3CX3N, where X is any amino acid, overview. The central cysteine (C385) of the motif is also involved in a disulfide bridge with C431. The enzyme aSMase contains a sphingolipid activator protein (saposin) domain in its N-terminal region followed by a proline-rich linker, this domain also plays a role in stabilizing the structure of the enzyme
additional information
-
homology model of aSMase enzyme with consensus motif NX3CX3N, where X is any amino acid, overview. The central cysteine (C385) of the motif is also involved in a disulfide bridge with C431. The enzyme aSMase contains a sphingolipid activator protein (saposin) domain in its N-terminal region followed by a proline-rich linker, this domain also plays a role in stabilizing the structure of the enzyme
additional information
isozyme Sph2 structure homology modeling, the isozyme Sph2 is unique and possesses the Mg2+-binding Glu53 residue in the metal-binding site and two His residues, His151 and His286, in the catalytic site
additional information
-
isozyme Sph2 structure homology modeling, the isozyme Sph2 is unique and possesses the Mg2+-binding Glu53 residue in the metal-binding site and two His residues, His151 and His286, in the catalytic site
-
additional information
-
establishing enzyme activity in lipid vesicles, method development, overview. Both lipase activities are sensitive to vesicle size, but in opposite ways: while phospholipase C is higher with larger vesicles, sphingomyelinase activity is lower
-
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D100A
-
site-directed mutagenesis, mutation in close proximity to Mg2+ at the side-edge, the mutant shows reduced binding to and hydrolysis of sphingomyelin in membranes of sheep erythrocytes or SM-liposomes, similar catalytic activity compared to the wild-type enzyme
E53D
-
5% of wild-type sphingomyelin hydrolyzing activity, E53 acts as an indespensable ligand of Mg2+ essential for catalytic activity
E53Q
-
no sphingomyelin hydrolyzing and no hemolytic activity, E53 acts as an indespensable ligand of Mg2+ essential for catalytic activity
E99A
-
site-directed mutagenesis, mutation in close proximity to Mg2+ at the side-edge, the mutant shows reduced binding to and hydrolysis of sphingomyelin in membranes of sheep erythrocytes or SM-liposomes, similar catalytic activity compared to the wild-type enzyme
F55A
-
site-directed mutagenesis, the mutation in close proximity to Mg2+ at the side-edge does not affect the enzyme
H151D
-
no nSMase activity
H151E
-
no nSMase activity
H151F
-
no nSMase activity
H151K
-
no nSMase activity
H151N
-
no nSMase activity
H151Q
-
8.3% of wild-type nSMase activity
H151R
-
no nSMase activity
H151Y
-
no nSMase activity
N57A
-
site-directed mutagenesis, mutation in close proximity to Mg2+ at the side-edge, the mutant shows reduced binding to and hydrolysis of sphingomyelin in membranes of sheep erythrocytes or SM-liposomes, mutant N57A loses the metal ion at the side-edge, similar catalytic activity compared to the wild-type enzyme
D100A
-
site-directed mutagenesis, mutation in close proximity to Mg2+ at the side-edge, the mutant shows reduced binding to and hydrolysis of sphingomyelin in membranes of sheep erythrocytes or SM-liposomes, similar catalytic activity compared to the wild-type enzyme
-
E53A
-
site-directed mutagenesis, inactive mutant
-
E99A
-
site-directed mutagenesis, mutation in close proximity to Mg2+ at the side-edge, the mutant shows reduced binding to and hydrolysis of sphingomyelin in membranes of sheep erythrocytes or SM-liposomes, similar catalytic activity compared to the wild-type enzyme
-
F285A
-
site-directed mutagenesis, binding of the mutant enzyme to mouse macrophages decreases markedly in comparison to the binding by wild-type enzyme
-
F55A
-
site-directed mutagenesis, the mutation in close proximity to Mg2+ at the side-edge does not affect the enzyme
-
N57A
-
site-directed mutagenesis, mutation in close proximity to Mg2+ at the side-edge, the mutant shows reduced binding to and hydrolysis of sphingomyelin in membranes of sheep erythrocytes or SM-liposomes, mutant N57A loses the metal ion at the side-edge, similar catalytic activity compared to the wild-type enzyme
-
W284A
-
site-directed mutagenesis, binding of the mutant enzyme to mouse macrophages decreases markedly in comparison to the binding by wild-type enzyme
-
H148G
-
mutant enzyme shows no sphingomyelinase activity
Y57A
-
mutant enzyme shows 111.3% of wild-type sphingomyelinase activity
Y57C/C169L
-
mutant enzyme shows 104.1% of wild-type sphingomyelinase activity
Y57F
-
mutant enzyme shows 105.2% of wild-type sphingomyelinase activity
Y57L
-
mutant enzyme shows 103.1% of wild-type sphingomyelinase activity
Y65A
-
mutant enzyme shows 89.4% of wild-type sphingomyelinase activity
Y65C/C169L
-
mutant enzyme shows 98.1% of wild-type sphingomyelinase activity
Y65F
-
mutant enzyme shows 95.6% of wild-type sphingomyelinase activity
Y65L
-
mutant enzyme shows 99.2% of wild-type sphingomyelinase activity
H272A
mutant shows reduced activity
C120S
-
mutant enzyme is almost completely devoid of activity in the detergent-containing micellar assay system as well as in the liposomal assay system in the presence of saposin C
C131S
-
mutant enzyme is almost completely devoid of activity in the detergent-containing micellar assay system as well as in the liposomal assay system in the presence of saposin C
C1A
-
site-directed mutagenesis, the altered residue shows altered palmitoylationin the mutant
C2A
-
site-directed mutagenesis, the altered residue shows altered palmitoylationin the mutant
C3A
-
site-directed mutagenesis, the altered residue shows altered palmitoylationin the mutant
C3A/C392A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C3A/C395A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C3A/C395A/C396A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C3A/C396A C3A/C400A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C3A/C5A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C4A
-
site-directed mutagenesis, the altered residue shows altered palmitoylationin the mutant
C5A
-
site-directed mutagenesis, the altered residue shows altered palmitoylationin the mutant
C5A/C53A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C5A/C53A/C54A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C5A/C53A/C59A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C5A/C54A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C5A/C54A/C59A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C5A/C59A
-
site-directed mutagenesis, the altered residues show altered palmitoylationin the mutant
C617Y
-
the mutation is associated with leukemia
C629S
-
5fold increase in activity, modification or deletion of the thiol group on the C-terminal cysteine leads to activation of rhASM
C78N
-
reduced alk-SMase activity
D194N
-
the mutation is associated with leukemia
D199A
-
mutation of the metal binding site of alk-SMase abolishes the enzyme activity
D358G
-
the mutation is associated with leukaemia and causes protein instability
D51N
-
the mutation is associated with leukemia
E499G
-
the mutation is associated with leukemia
E49Q
-
complete loss of hnSMase activity
F572L
naturally occuring mutation, reconstructed by site-directed mutagenesis, involved in acid sphingomyelinase deficiency and subsequently in Niemann-Pick disease, marked deficiency of enzyme activity consistent with the disease phenotype in cells homoallelic for the mutation
G195E
-
the mutation is associated with leukemia
G247D
naturally occuring mutation, reconstructed by site-directed mutagenesis, involved in acid sphingomyelinase deficiency and subsequently in Niemann-Pick disease, marked deficiency of enzyme activity consistent with the disease phenotype in cells homoallelic for the mutation
G248S
-
the mutation is associated with leukemia
G508R
-
naturally occuring polymorphisms in the SMPD1 gene, the G1522A and a hexanucleotide repeat sequence within the signal peptide region, are investigated in 118 unrelated individuals of French Canadian descent with low plasma levels of HDL-cholesterol, allele frequency, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
G577A
-
naturally occuring mutation, the mutant has severely defective enzymatic function
H272N
-
complete loss of hnSMase activity
H353A
-
inactive mutant enzyme
K104A
-
mutation does not result in any altered activity
K105A
-
intracellular activity is not reduced but zinc-responsive secreted activity is reduced
K118A
-
intracellular activity is not reduced but zinc-responsive secreted activity is reduced
K118E
-
mutant enzyme is almost completely devoid of activity in the detergent-containing micellar assay system as well as in the liposomal assay system in the presence of saposin C
K124A
-
intracellular activity is not reduced but zinc-responsive secreted activity is reduced
K183A
-
intracellular activity is not reduced but zinc-responsive secreted activity is reduced
K187A
-
intracellular activity is reduced but zinc-responsive secreted activity is unchanged
K249A
-
intracellular activity and zinc-responsive secreted activity are both reduced
K305A
-
intracellular activity and zinc-responsive secreted activity are both reduced
K346A
-
intracellular activity is reduced but zinc-responsive secreted activity is unchanged
K419A
-
intracellular activity and zinc-responsive secreted activity are both reduced
K433A
-
intracellular activity and zinc-responsive secreted activity are both reduced
K576A
-
intracellular activity and zinc-responsive secreted activity are both reduced
K93A
-
mutant enzyme has reduced intracellular activity, but enhanced zinc-responsive secreted activity
M74K
-
reduced alk-SMase activity
N180H
-
complete loss of hnSMase activity
O153A
-
mutant enzyme still exhibits enzyme activity of approximately 52% of normal in a detergent-containing micellar assay, but only 13% of normal activity in a detergent-free liposomal assay system. Addition of saposin C to the liposomal ass mixture increases activity of the mutant enzyme to 46% of normal. Saposin C does not result in complete restoration of the variant activity
R246C
-
the mutation is associated with leukemia
R336C
-
the mutation is associated with leukemia
R496L
-
naturally occuring mutation, the mutant has severely defective enzymatic function
S248R
naturally occuring mutation, reconstructed by site-directed mutagenesis, involved in acid sphingomyelinase deficiency and subsequently in Niemann-Pick disease, marked deficiency of enzyme activity consistent with the disease phenotype in cells homoallelic for the mutation
S508A
-
site-directed mutagenesis of ASMase, the mutation blocks the ceramide formation after phorbol 12-myristate 13-acetate treatment, the mutant acts dominantly negative
S76F
-
alk-SMase activity is abolished
V131L
-
the mutation is associated with leukemia
V507I
-
the mutation is associated with leukemia
W391G
naturally occuring mutation, reconstructed by site-directed mutagenesis, involved in acid sphingomyelinase deficiency and subsequently in Niemann-Pick disease, marked deficiency of enzyme activity consistent with the disease phenotype in cells homoallelic for the mutation
Y109L
the mutation mutant decreases the hydrolysis rate of sphingomyelin and 4-nitrophenylphosphorylcholine 5-10fold compared to the wild type enzyme
Y166L
the mutation mutant decreases the hydrolysis rate of sphingomyelin and 4-nitrophenylphosphorylcholine 5-10fold compared to the wild type enzyme
Y43H
-
the mutation is associated with leukemia
Y537H
-
naturally occuring mutation, the mutant has severely defective enzymatic function
Y95F
-
the mutation is associated with leukemia
C617S
site-directed mutagenesis, gain-of-function mutation associated with a decreased propensity for oligomerization
F388R
the mutant shows reduced activity with sphingomyelin and bis(4-nitrophenyl)phosphate as substrate as compared to the wild type enzyme
H280A
inactive with sphingomyelin and bis(4-nitrophenyl)phosphate as substrate
H317A
inactive with sphingomyelin as substrate, but active with bis(4-nitrophenyl)phosphate as substrate as compared to the wild type enzyme
K140M
the mutant shows reduced activity compared to the wild type enzyme
K140M/N141A
almost inactive
L391R
the mutant shows about 20% activity with sphingomyelin and about 50% activity with bis(4-nitrophenyl)phosphate as substrate, as compared to the wild type enzyme
N141A
the mutant shows reduced activity compared to the wild type enzyme
N200A
the mutant shows increased activity compared to the wild type enzyme
P321E
the mutant shows reduced activity with sphingomyelin and almost no activity with bis(4-nitrophenyl)phosphate as substrate, compared to the wild type enzyme
V128E
the mutant shows about 20% activity with sphingomyelin and about 70% activity with bis(4-nitrophenyl)phosphate as substrate as compared to the wild type enzyme
V143R
the mutant shows about 5% activity with sphingomyelin and about 65% activity with bis(4-nitrophenyl)phosphate as substrate as compared to the wild type enzyme
W283N
the mutant shows reduced activity with sphingomyelin and bis(4-nitrophenyl)phosphate as substrate as compared to the wild type enzyme
Y198F
the mutant shows reduced activity compared to the wild type enzyme
D199A
-
mutation abolishes hydrolysis of platelet-activating factor
D246A
-
mutation abolishes hydrolysis of platelet-activating factor
E53A
-
no sphingomyelin hydrolyzing and no hemolytic activity, E53 acts as an indespensable ligand of Mg2+ essential for catalytic activity
E53A
-
site-directed mutagenesis, inactive mutant
F285A
catalytic activity of the mutant enzyme is below the detection limit, affinity of mutant enzyme to sphingomyelin liposomes are much weaker than the wild-type enzyme
F285A
-
site-directed mutagenesis, binding of the mutant enzyme to mouse macrophages decreases markedly in comparison to the binding by wild-type enzyme
H151A
-
0.6% of wild-type nSMase activity
H151A
-
mutation inactivates the sphingomyelinase activity and also abolishes the insecticidal activity
W284A
catalytic activity of the mutant enzyme is below the detection limit, affinity of mutant enzyme to sphingomyelin liposomes are much weaker than the wild-type enzyme
W284A
-
site-directed mutagenesis, binding of the mutant enzyme to mouse macrophages decreases markedly in comparison to the binding by wild-type enzyme
additional information
-
microinjection of the Bacillus cereus neutral sphingomyelinase in Xenopus laevis oocytes results in increased ceramide levels and triggered germinal vesicle breakdown and oxidant-dependent apoptosis, overview
additional information
mutation of the two histidines, His134 and His252, abolished enzyme activity
additional information
-
mutation of the two histidines, His134 and His252, abolished enzyme activity
-
additional information
-
acid sphingomyelinase, ASM, downregulation by specific siRNA leads to reduced FasL-induced lipid raft clustering and Fas aggregation on endothelial cell membrane
additional information
enzyme knockdown by siRNA
additional information
enzyme knockdown by siRNA
additional information
enzyme knockdown by siRNA
additional information
enzyme knockdown by siRNA
additional information
-
aSMase silencing by siRNA in human airway epithelial cells leads to increased caspase-3 cleavage
additional information
-
DELTAR608 is a naturally occuring deletion mutation, construction of five serial carboxyl-terminal deletion mutants N620, N590, N570, N510, and N490, none of which, except the smallest deletion mutant N620 that preserves all post-translational modifications, are found capable of secretion to the medium, only the N620 deletion mutant conserves functional integrity with 100% wild type activity, all other mutants completely loose the ability to catalyze sphingomyelin hydrolysis, mutant DELTAR608 transfected CHO cells and fibroblasts from a compound heterozygous Niemann-Pick disease type B patient, DELTAR608 and R441X, have defective translocation to the plasma membrane, deletion mutants DELTAR608 and N590 are trapped in the endoplasmic reticulum quality control checkpoint in contrast to the wild-type lysosomal localization, steady-state levels of ubiquitination are minimal for the wild-type ASM, a significant amount of Lys63-linked polyubiquitinated DELTAR608 and N590 can be purified by S5a-affinity chromatography, indicating an important misfolding in the carboxyl-terminal mutants
additional information
-
downregulation of N-SMase2 by siRNA leads to inhibition of TNFalpha-induced activation of endothelial nitric oxide synthase in the sphingomyelin and ceramide metabolism, overview
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
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
additional information
-
microinjection of the human acidic sphingomyelinase in Xenopus laevis oocytes results in increased ceramide levels and triggered germinal vesicle breakdown and oxidant-dependent apoptosis, overview
additional information
naturally occuring mutant enzyme forms in the liver are full-length enzymes which contain an additional 73 amino acid sequence at the N-terminus that reduces the enzyme activity, overview
additional information
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naturally occuring mutant enzyme forms in the liver are full-length enzymes which contain an additional 73 amino acid sequence at the N-terminus that reduces the enzyme activity, overview
additional information
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silencing of ASMase by siRNA
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siRNA knockdown of both nSMase2 and aSMase, silencing nSMase2 prevents H2O2-induced apoptosis, but has no effect on ONOO--induced apoptosis, while silencing of aSMase markedly impairs ONOO--induced apoptosis, but does not affect H2O2-induced apoptosis
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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
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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
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knockdown of the nezyme by siRNA, The TNF receptor 1 is migrated into the lipid raft in diethyl malate-treated cells or ASMase-overexpressing cells
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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
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targeted knock-out mutations of LIPI-2 genes, including gene smcL, cause virulence defects, overview
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targeted knock-out mutations of LIPI-2 genes, including gene smcL, cause virulence defects, overview
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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
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additional information
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ASMase knockdown by siRNA decreases ceramide generation during ischemia/reperfusion, and attenuates serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 and JNK activation, ASMase down-regulation by siRNA protects the liver against ischemia/reperfusion-induced damage, overview
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construction of nSMase2 and of nSMase1 knockout mice, the latter do not show lipid storage abnormalities nor deficient sphingomyelin metabolism, phenotype, overview
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extracts from ASM-deficient macrophages sustain limited enzymatic synthesis of NBD-ceramide from NBD-sphingomyelin, phenotypes of ASM-/- and ASM+/+ macrophages, intracellular survival of Salmonella enterica serovar typhimurium is enhanced in macrophages lacking ASM, overview
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generation of ASM knockdown cells by specific shRNA
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C-Terminal deletion mutants lose sphingomyelinase activity for hydrolysis of intact erythrocytes
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construction of nSMase2 knockout mice
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overexpression of NSMase-2 in hepatocytes from young rats leads both to a reduction in IRAK-1 degradation and potentiation of JNK phosphorylation, mimicking that seen in hepatocytes from old animals, overview, inhibition of NSMase activity in hepatocytes from aged rats using siRNA leads to reversion to the young phenotype of IL-1beta response, overview
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