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Information on EC 3.1.4.12 - sphingomyelin phosphodiesterase and Organism(s) Rattus norvegicus and UniProt Accession Q9ET64
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3.1.4.12 sphingomyelin phosphodiesteraseIUBMB Comments
Has very little activity on phosphatidylcholine.
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Word Map
- 3.1.4.12
- aureus
- lysosomal
- sphingolipids
- niemann-pick
- cholesterol
-
staphylococcal
- necrosis
- clostridium
- phospholipid
- endothelial
- sphingosine
- perfringens
- phosphatidylcholine
- erythrocyte
-
permeabilized
- ceramidase
-
raft
-
hemolytic
- tnf-alpha
- c2-ceramide
-
bilayer
-
pore-forming
- sphingosine-1-phosphate
- venom
-
cell-permeable
- phosphatidylserine
- desipramine
- scorpion
- glucosylceramide
-
microdomains
- enterotoxin
-
ceramide-induced
- phospholipases
- fumonisin
- phosphorylcholine
-
hepatosplenomegaly
- amitriptyline
- imipramine
- gangrene
-
cytolysin
-
dermonecrosis
- glucocerebrosidase
- pc-plc
- gaucher
-
phosphatidylcholine-specific
-
leukocidins
- lecithinase
- coagulase
- pharmacology
-
nonhemolytic
- drug development
- diagnostics
- medicine
-
transbilayer
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
sphingomyelinase, alpha-toxin, acid sphingomyelinase, smase, neutral sphingomyelinase, asmase, nsmase2, nsmase, smpd1, n-smase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acid sphingomyelinase
alkaline sphingomyelinase
aSMase
Beta-hemolysin
-
-
-
-
Beta-toxin
-
-
-
-
Lyso-PAF-PLC
-
-
-
-
N-SMase
neutral sphingomyelinase
nSMase
phosphodiesterase, sphingomyelin
-
-
-
-
SMase
SMPLC
-
-
-
-
sphingomyelin phosphodiesterase
-
-
-
-
sphingomyelinase
-
-
-
-
sphingomyelinase C
-
-
-
-
additional information
-
alk-SMase is a member of the NPP, i.e. nucleotide diphosphatase/phosphodiesterase, family
acid sphingomyelinase
-
-
-
-
alkaline sphingomyelinase
-
-
-
-
aSMase
-
-
-
-
N-SMase
-
-
-
-
neutral sphingomyelinase
-
-
-
-
neutral sphingomyelinase
-
-
nSMase
-
-
-
-
SMase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
sphingomyelin cholinephosphohydrolase
Has very little activity on phosphatidylcholine.
CAS REGISTRY NUMBER
COMMENTARY
9031-54-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
1-alkyl-lyso-platelet activating factor + H2O
1-alkylglycerol + choline phosphate
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
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-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
8% of activity with sphingomyelin
-
?
sphingomyelin + H2O
?
-
-
-
-
?
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
-
-
?
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
-
-
?
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
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
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
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
-
-
?
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mn2+
Zn2+
Zn2+
-
activates the alk-SMase activity with platelet-inactivating factor, mutation of the metal binding site of alk-SMase abolishes the enzyme activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
arachidonic acid
-
slight stimulation below 0.8 mM, approx. 50% inhibition at 3.2 mM
cis, cis-cyclohexane 1,3,5-trisphosphate
-
barely inhibits aSMase even at a 0.1 mM concentration
D609
-
48% inhibition of the enzyme in chromain after 30 min of treatment, no inhibition by D609 in the nuclear membrane
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
phosphatidyl inositol 3,5-bisphosphate
-
potent selective acid sphingomyelinase inhibitor
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
stearic acid
-
slight stimulation below 0.8 mM, approx. 10% 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
-
-
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
EDTA
-
inhibits hydrolysis of platelet-activating factor, no effect on hydrolysis of sphingomyelin
scyphostatin
-
specific inhibitor of neutral sphingomyelinase, prevents mechanoactivation of neutral sphingomyelinase
scyphostatin
-
inhibition of NSMase activity in hepatocytes from aged rats using leads to reversion to the young phenotype of IL-1beta response
sphingomyelin
-
strong competitive inhibition of platelet-inactivating factor hydrolysis
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+
-
0.1-0.25 mM inhibits hydrolysis of platelet-activating factor, concentrations above 0.25 mM inhibit hydrolysis of sphingomyelin and platelet-activating factor
additional information
-
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
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
Bile salts
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
choline
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
phosphatidylcholine-specific phospholipase C
-
increases the N-SMase activity up to 2fold
-
tumor necrosis factor-alpha
-
activates neutral spingomyelinase in a multiphasic manner
-
bile salt
-
dependent on, particularly taurocholate and taurochenodeoxycholate
taurochenodeoxycholate
-
strong activation, maximal activation at approx. 2 mM
taurochenodeoxycholate
-
stimulates hydrolysis of sphingomyelin and platelet-activating factor
taurocholate
-
stimulates hydrolysis of sphingomyelin and platelet-activating factor
taurocholate
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
1,3,5-tri-O-dodecylsulfonyl-D_myo-inositol
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.1
1,3,5-tri-O-ethylsulfonyl-D-myo-inositol
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.1
1,3,5-tri-O-methylsulfonyl-D-myo-inositol
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.1
1,3,5-tri-O-octylsulfonyl-D-myo-inositol
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.0009
1-O-dodecylsulfonyl-D-myo-inositol 3,5-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.1
1-O-ethylsulfonyl-D-myo-inositol 3,5-bisphosphate
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.043
1-O-hexylsulfonyl-D-myo-inositol 3,5-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.1
1-O-methylsulfonyl-D-myo-inositol 3,5-bisphosphate
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.004
1-O-octylsulfonyl-D-myo-inositol 3,5-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.00044
6-O-dodecylsulfonyl-D-glucose 2,4-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.0396
6-O-ethylsulfonyl-D-glucose 2,4-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.00416
6-O-hexylsulfonyl-D-glucose 2,4-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.00234
6-O-octylsulfonyl-D-glucose 2,4-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.1
cis, cis-cyclohexane 1,3,5-trisphosphate
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.1
myo-Inositol 3,5-bisphosphate
Rattus norvegicus
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37°C
0.00093
phosphatidyl inositol 3,5-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 8.4
-
approx. 25% of maximal actiity at pH 6.0, approx. 75% of maximal activity at pH 8.0
6 - 10
-
almost no activity at pH 6.0, approx. 60% of maximal activity at pH 7.5, approx. 90% of maximal activity at Ph 10.0
6 - 9
-
pH 6.0: about 55% of maximal activity, pH 9.0: about 35% of maximal activity, hydrolysis of platelet-activating factor
6.5 - 9.5
-
approx. 25% of maximal activity at pH 6.5, approx. 55% of maximal activity at pH 9.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in hippocampus the enzyme activity is significantly higher than in striatum and cortex. Significant increase in cortical membrane-associated N-Sase activity with age
-
in hippocampus the enzyme activity is significantly higher than in striatum and cortex. Age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
-
in hippocampus the enzyme activity is significantly higher than in striatum and corte. Age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
additional information
-
intraluminal, intestinal microvillar membrane, and mucosa, in the intestinal tract, the activity of alkaline SMase is much higher than the activity of neutral and acid SMase, overview
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
-
exclusively expressed in intestine, lack of bSMase may be related to colon carcinogenesis
additional information
-
maximum activity in the distal jejunum, little activity in bile, liver, pancreas after trypsin treatment
additional information
-
Alk-SMase developmental enzyme activity, overview, Alk-SMase activity decreases with age
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
neutral sphingomyelinase is concentrated at the endothelial cell surface in caveolae
-
neutral sphingomyelinase is concentrated at the endothelial cell surface in caveolae
-
inner lysosomal membrane, detachment caused by weak bases inhibits the enzyme
-
age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
-
age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities. Significant increase in cortical membrane-associated N-Sase activity with age
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
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
-
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NSMA_RAT
422
2
47645
Swiss-Prot
Mitochondrion (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
-
plasma membrane and microsomes, 10 min, 15% activity, lysosomes, 10 min, 78% activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Triton X-100, DEAE-Sephacel, heparin-Sepharose, hydroxyapatite, Mono Q, Phenyl-Sepharose, Superose 12
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of nSMase1, the recombinant enzyme shows altered subcellular localization in the endoplasmic reticulum compared to the wild-type nSMase1 localized in the nucleus
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
acid SMase protein is decreased by 25% in the intestine and by 34% in the liver at 0.1 mM ezetimibe
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
inhibiting or stopping N-SMase activity is an important strategy to prevent neuron death from ischemia
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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Rattus norvegicus
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Rattus norvegicus
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Rattus norvegicus
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Rattus norvegicus
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Rattus norvegicus
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Rattus norvegicus
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Rattus norvegicus
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Biochemical and immunological characterization of the DNA binding protein (RBP-Jk) to mouse Jk recombination signal sequence
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112
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1992
Rattus norvegicus
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Characterization of the neutral pH-optimum sphingomyelinase from rat brain: inhibition by copper II and ganglioside GM3
Biochim. Biophys. Acta
1165
314-320
1993
Rattus norvegicus
Duan, R.D.; Nyberg, L.; Nilsson, A.
Alkaline sphingomyelinase activity in rat gastrointestinal tract: distribution and characteristics
Biochim. Biophys. Acta
1259
49-55
1995
Rattus norvegicus
Liu, B.; Hassler, D.F.; Smith, G.K.; Weaver, K.; Hannun, Y.A.
Purification and characterization of a membrane bound neutral pH optimum magnesium-dependent and phosphatidylserine-stimulated sphingomyelinase from rat brain
J. Biol. Chem.
273
34472-34479
1998
Rattus norvegicus
Mizutani, Y.; Tamiya-Koizumi, K.; Irie, F.; Hirabayashi, Y.; Miwa, M.; Yoshida, S.
Cloning and expression of rat neutral sphingomyelinase: enzymological characterization and identification of essential histidine residues
Biochim. Biophys. Acta
1485
236-246
2000
Rattus norvegicus
Goni, F.M.; Alonso, A.
Sphingomyelinases: enzymology and membrane activity
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531
38-46
2002
Bos taurus, Rattus norvegicus
Mizutani, Y.; Tamiya-Koizumi, K.; Nakamura, N.; Kobayashi, M.; Hirabayashi, Y.; Yoshida, S.
Nuclear localization of neutral sphingomyelinase 1: biochemical and immunocytochemical analyses
J. Cell Sci.
114
3727-3736
2001
Rattus norvegicus (Q9ET64)
Cheng, Y.; Nilsson, A.; Tomquist, E.; Duan, R.D.
Purification, characterization, and expression of rat intestinal alkaline sphingomyelinase
J. Lipid Res.
43
316-324
2002
Rattus norvegicus
Won, J.S.; Im, Y.B.; Khan, M.; Singh, A.K.; Singh, I.
The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide-mediated expression of inducible nitric oxide synthase
J. Neurochem.
88
583-593
2004
Rattus norvegicus
Liu, J.J.; Nilsson, A.; Duan, R.D.
In vitro effects of fat, FA, and cholesterol on sphingomyelin hydrolysis induced by rat intestinal alkaline sphingomyelinase
Lipids
37
469-474
2002
Rattus norvegicus
Liu, B.; Hannun, Y.A.
Purification of rat brain membrane neutral sphingomyelinase
Methods Enzymol.
311
156-164
2000
Rattus norvegicus
Czarny, M.; Schnitzer, J.E.
Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium
Am. J. Physiol.
287
H1344-1352
2004
Rattus norvegicus
Wu, J.; Nilsson, A.; Jonsson, B.A.; Stenstad, H.; Agace, W.; Cheng, Y.; Duan, R.D.
Intestinal alkaline sphingomyelinase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity
Biochem. J.
394
299-308
2006
Homo sapiens, Rattus norvegicus
Karakashian, A.A.; Giltiay, N.V.; Smith, G.M.; Nikolova-Karakashian, M.N.
Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-beta-induced JNK activation
FASEB J.
18
968-970
2004
Rattus norvegicus
Testai, F.D.; Landek, M.A.; Dawson, G.
Regulation of sphingomyelinases in cells of the oligodendrocyte lineage
J. Neurosci. Res.
75
66-74
2004
Homo sapiens, Rattus norvegicus
Soeda, S.; Tsuji, Y.; Ochiai, T.; Mishima, K.; Iwasaki, K.; Fujiwara, M.; Yokomatsu, T.; Murano, T.; Shibuya, S.; Shimeno, H.
Inhibition of sphingomyelinase activity helps to prevent neuron death caused by ischemic stress
Neurochem. Int.
45
619-626
2004
Rattus norvegicus
Crivello, N.A.; Rosenberg, I.H.; Dallal, G.E.; Bielinski, D.; Joseph, J.A.
Age-related changes in neutral sphingomyelin-specific phospholipase C activity in striatum, hippocampus, and frontal cortex: implication for sensitivity to stress and inflammation
Neurochem. Int.
47
573-579
2005
Rattus norvegicus, Rattus norvegicus Fischer 344
Albi, E.; Lazzarini, R.; Viola Magni, M.
Phosphatidylcholine/sphingomyelin metabolism crosstalk inside the nucleus
Biochem. J.
410
381-389
2008
Rattus norvegicus
Clarke, C.J.; Snook, C.F.; Tani, M.; Matmati, N.; Marchesini, N.; Hannun, Y.A.
The extended family of neutral sphingomyelinases
Biochemistry
45
11247-11256
2006
Helicobacter pylori, Staphylococcus aureus, Rattus norvegicus, Homo sapiens (O60906), Homo sapiens (Q9NY59), Bacillus cereus (P09599), Listeria ivanovii (Q9RLV9), Listeria ivanovii nSMase (Q9RLV9), Helicobacter pylori nSMase, Bacillus cereus nSMase (P09599)
Clarke, C.J.; Hannun, Y.A.
Neutral sphingomyelinases and nSMase2: bridging the gaps
Biochim. Biophys. Acta
1758
1893-1901
2006
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Duan, R.D.; Verkade, H.J.; Cheng, Y.; Havinga, R.; Nilsson, A.
Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase
Biochim. Biophys. Acta
1771
196-201
2007
Rattus norvegicus
Duan, R.
Sphingomyelinase and ceramidase in the intestinal tract
Eur. J. Lipid Sci. Technol.
109
987-993
2007
Homo sapiens, Mus musculus, Rattus norvegicus
-
Rutkute, K.; Karakashian, A.A.; Giltiay, N.V.; Dobierzewska, A.; Nikolova-Karakashian, M.N.
Aging in rat causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2
Hepatology
46
1166-1176
2007
Rattus norvegicus
Rutkute, K.; Asmis, R.H.; Nikolova-Karakashian, M.N.
Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation
J. Lipid Res.
48
2443-2452
2007
Rattus norvegicus
Kornhuber, J.; Tripal, P.; Reichel, M.; Terfloth, L.; Bleich, S.; Wiltfang, J.; Gulbins, E.
Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model
J. Med. Chem.
51
219-237
2008
Homo sapiens, Rattus norvegicus
Adamy, C.; Mulder, P.; Khouzami, L.; Andrieu-abadie, N.; Defer, N.; Candiani, G.; Pavoine, C.; Caramelle, P.; Souktani, R.; Le Corvoisier, P.; Perier, M.; Kirsch, M.; Damy, T.; Berdeaux, A.; Levade, T.; Thuillez, C.; Hittinger, L.; Pecker, F.
Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats
J. Mol. Cell. Cardiol.
43
344-353
2007
Homo sapiens, Rattus norvegicus
Roth, A.G.; Redmer, S.; Arenz, C.
Development of carbohydrate-derived inhibitors of acid sphingomyelinase
Bioorg. Med. Chem.
18
939-944
2010
Rattus norvegicus
Roth, A.G.; Redmer, S.; Arenz, C.
Potent inhibition of acid sphingomyelinase by phosphoinositide analogues
ChemBioChem
10
2367-2374
2009
Rattus norvegicus
Cheng, Y.; Liu, F.; Wu, J.; Zhang, Y.; Nilsson, A.; Duan, R.D.
Ezetimibe inhibits expression of acid sphingomyelinase in liver and intestine
Lipids
44
897-906
2009
Homo sapiens, Rattus norvegicus
Osawa, Y.; Seki, E.; Kodama, Y.; Suetsugu, A.; Miura, K.; Adachi, M.; Ito, H.; Shiratori, Y.; Banno, Y.; Olefsky, J.M.; Nagaki, M.; Moriwaki, H.; Brenner, D.A.; Seishima, M.
Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression
FASEB J.
25
1133-1144
2011
Mus musculus, Mus musculus C57/BL6J, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
EXTERNAL LINKS (specific for EC-Number 3.1.4.12)
Transporter Classification Database (TCDB): 1.B.79.1.1, 1.C.67.1.2
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