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Information on EC 3.1.4.12 - sphingomyelin phosphodiesterase
for references in articles please use BRENDA:EC3.1.4.12
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EC Tree 3 Hydrolases
3.1 Acting on ester bonds
3.1.4 Phosphoric-diester hydrolases
3.1.4.12 sphingomyelin phosphodiesterase
IUBMB Comments
Has very little activity on phosphatidylcholine.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 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
showSynonyms
sphingomyelinase, alpha-toxin, acid sphingomyelinase, smase, neutral sphingomyelinase, asmase, nsmase2, nsmase, n-smase, smpd1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A-SMase
acid SMase
acid sphingomyelinase
acidic SMase
acidic sphingomyelinase
alk-SMase
alkaline SMase
alkaline sphingomyelinase
alpha-toxin
ASM
aSMase
Bc-SMase
Beta-hemolysin
-
-
-
-
Beta-toxin
-
-
-
-
bSMase
ceramide-phosphocholine phosphodiesterase
intestinal alkaline sphingomyelinase
Lyso-PAF-PLC
-
-
-
-
magnesium-dependent neutral sphingomyelinase
Mg++-dependent sphingomyelinase
N-Sase
N-SMase
neutral SMase
neutral sphingomyelin-specific phospholipase C
neutral sphingomyelinase
neutral sphingomyelinase 1
neutral sphingomyelinase 2
neutral sphingomyelinase-2
neutral sphingomyelinase-3
neutral sphingomyelinase-C
nSMase
NSMase-2
nSMase1
nSMase2
nSMase3
phosphodiesterase, sphingomyelin
-
-
-
-
PLC
PlcH
PlcHR2
S-SMase
SMase
SMase-C
SMC
SmcL
SMPD1
Smpd3
SMPLC
-
-
-
-
Sph2
sphingomyelin phosphodiesterase
-
-
-
-
sphingomyelin phosphodiesterase 1
sphingomyelinase
sphingomyelinase C
additional information
acid sphingomyelinase
-
-
-
-
acid sphingomyelinase
-
-
acid sphingomyelinase
-
-
alk-SMase
-
key enzyme in the intestinal tract for digestion of dietary sphingomyelin
alkaline sphingomyelinase
-
-
-
-
alkaline sphingomyelinase
-
key enzyme responsible for sphingomyelin digestion in the gut
aSMase
-
-
-
-
aSMase
-
-
N-SMase
-
-
-
-
neutral sphingomyelinase
-
-
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase 1
Q4LEU0
neutral SMase 1 acts as a mediator of stress-induced apoptosis
nSMase
-
-
-
-
PlcHR2
-
a phospholipase C/sphingomyelinase, the sphingomyelinase, but not the phospholipase C activity, is essential for hot-cold hemolysis
SMase
-
-
-
-
sphingomyelinase
-
-
-
-
sphingomyelinase
-
-
sphingomyelinase C
-
-
-
-
additional information
-
alk-SMase is a member of the NPP, i.e. nucleotide diphosphatase/phosphodiesterase, family
additional information
-
cf. EC 3.1.4.3, the enzyme is the prototype of another phosphatase superfamily
additional information
-
alk-SMase is a member of the NPP, i.e. nucleotide diphosphatase/phosphodiesterase, family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a sphingomyelin + H2O = a ceramide + phosphocholine
-
-
-
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, histidine residues, His136 and His272, are essential for catalysis
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, structure-function analysis, overview
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview
-
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, structure-function analysis, overview
-
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
additional information
-
SMase belongs to the family of interfacial enzymes that carry out processive catalytic turnover at the interface, SMase binds rapidly and avidly to sphingomyelin vesicles and it is fully active as a monomer at the interface
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PATHWAY SOURCE
PATHWAYS
MetaCyc
sphingolipid biosynthesis (mammals), sphingomyelin metabolism
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SYSTEMATIC NAME
IUBMB Comments
sphingomyelin cholinephosphohydrolase
Has very little activity on phosphatidylcholine.
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CAS REGISTRY NUMBER
COMMENTARY
9031-54-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1,2-dioleoyl-sn-glycero-3-phosphocholine + H2O
?
Substrates: 0.7% activity compared to sphingomyelin
Products: -
Products: -
?
1-alkyl-lyso-platelet activating factor + H2O
1-alkylglycerol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
1-O-octadecyl-2-lyso-platelet-activating factor + H2O
1-O-octadecyl-sn-glycerol + phosphocholine
Q4LEU0
Substrates: very little activity
Products: -
Products: -
?
2-(N-hexadecanoylamino)-4-nitrophenylphosphorylcholine + H2O
2-(N-hexadecanoylamino)-4-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
4-nitrobenz-2-oxa-1,3-diazole-sphingosylphosphorylcholine + H2O
4-nitrobenz-2-oxa-1,3-diazole-sphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
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
-
Substrates: -
Products: -
Products: -
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphocholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
Substrates: -
Products: -
Products: -
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + phosphorylcholine
-
Substrates: -
Products: -
Products: -
?
BODIPY FL C12-sphingomyelin + H2O
BODIPY FL C12-ceramide + phosphocholine
-
Substrates: -
Products: -
Products: -
?
BODIPYFL-C12-sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: -
Products: -
?
C6-7-nitro-2-1,3-benzoxadiazol-4-yl-sphingomyelin + H2O
?
Q4LEU0
Substrates: -
Products: -
Products: -
?
CDP-ethanolamine + H2O
CMP + phosphoethanolamine
Substrates: -
Products: -
Products: -
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
lissamine-rhodamine dodecanoyl sphingosyl phosphocholine + H2O
?
-
Substrates: neutral sphingomyelinase
Products: -
Products: -
?
lyso-platelet-activating factor + H2O
1-alkylglycerol + choline phosphate
-
Substrates: 103fold higher activity than with sphingomyelin in the absence of detergent
Products: -
Products: -
?
lyso-platelet-activating factor + H2O
alkylglycerol + choline phosphate
-
Substrates: 55% of activity with sphingomyelin in the absence of detergent
Products: -
Products: -
?
N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)-sphingosyl phosphocholine + H2O
?
-
Substrates: -
Products: -
Products: -
?
N-dodecanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-dodecanoylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
N-hexanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-hexanoylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
N-methyl-sphingomyelin + H2O
N-methyl-N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
p-nitrophenylphosphorylcholine + H2O
choline phosphate + p-nitrophenol
-
Substrates: -
Products: -
Products: -
?
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
-
Substrates: low activity
Products: -
Products: -
?
phosphatidylethanolamine + H2O
diacylglycerol + phosphorylethanolamine
-
Substrates: in the presence of 0.08% sodium taurodeoxycholate
Products: -
Products: -
?
sphingosylphosphorylcholine + H2O
sphingosine + choline phosphate
-
Substrates: 25% of activity with sphingomyelin
Products: -
Products: -
?
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
Substrates: 2.11% activity compared to sphingomyelin
Products: -
Products: -
?
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
Streptomyces griseocarneus NBRC13471
Substrates: 2.11% activity compared to sphingomyelin
Products: -
Products: -
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
Substrates: 9.04% activity compared to sphingomyelin
Products: -
Products: -
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
Streptomyces griseocarneus NBRC13471
Substrates: 9.04% activity compared to sphingomyelin
Products: -
Products: -
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
Substrates: 4.93% activity compared to sphingomyelin
Products: -
Products: -
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
Streptomyces griseocarneus NBRC13471
Substrates: 4.93% activity compared to sphingomyelin
Products: -
Products: -
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine + H2O
?
-
Substrates: -
Products: -
Products: -
?
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine + H2O
?
-
Substrates: -
Products: -
Products: -
?
4-nitrophenyl phosphorylcholine + H2O
4-nitrophenol + phosphorylcholine
-
Substrates: -
Products: -
Products: -
?
4-nitrophenyl phosphorylcholine + H2O
4-nitrophenol + phosphorylcholine
Substrates: -
Products: -
Products: -
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
Substrates: -
Products: -
Products: -
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine, ceramide colocalizes with acetylated tubulin in primary cilia and the mitotic spindle of human embryonic stem cells
Products: 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
-
Substrates: 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
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: using radiolabelled C12-sphingomyelin as substrate
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: 6-N-(7-nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: i.e. an N-acylsphingosine
Products: i.e. an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: 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
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: 6-N-(7-N´nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
-
Substrates: -
Products: -
Products: -
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
-
Substrates: poor substrate
Products: -
Products: -
?
bis-p-nitrophenyl phosphate + H2O
?
-
Substrates: poor substrate
Products: -
Products: -
?
choline-methyl-sphingomyelin + H2O
?
Q4LEU0
Substrates: high activity
Products: -
Products: -
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
L-alpha-phosphatidylinositol + H2O
?
Substrates: 5.63% activity compared to sphingomyelin
Products: -
Products: -
?
L-alpha-phosphatidylinositol + H2O
?
Streptomyces griseocarneus NBRC13471
Substrates: 5.63% activity compared to sphingomyelin
Products: -
Products: -
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
Substrates: 198fold higher activity than with sphingomyelin in the absence of detergent
Products: -
Products: -
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
Substrates: 580% of activity with sphingomyelin in the absence of detergent
Products: -
Products: -
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
Substrates: 8% of activity with sphingomyelin
Products: -
Products: -
?
phosphatidylcholine + H2O
?
Substrates: the phosphatidylcholinesterase activity of the enzyme is five-fold higher than the sphingomyelinase C activity
Products: -
Products: -
?
phosphatidylcholine + H2O
?
Substrates: the phosphatidylcholinesterase activity of the enzyme is five-fold higher than the sphingomyelinase C activity
Products: -
Products: -
?
phosphatidylcholine + H2O
?
Substrates: both PC and SM bind to a similar location of the phosphate-interacting and activesites residues
Products: -
Products: -
?
phosphatidylcholine + H2O
?
Substrates: both PC and SM bind to a similar location of the phosphate-interacting and activesites residues
Products: -
Products: -
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
Substrates: in the presence of 0.08% sodium taurodeoxycholate
Products: -
Products: -
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
Substrates: -
Products: -
Products: -
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
Substrates: 8% of activity with sphingomyelin
Products: -
Products: -
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
-
Substrates: in the presence of 0.08% sodium taurodeoxycholate
Products: -
Products: -
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
-
Substrates: in the absence of detergents an in the presence of 0.05% Nonidet P-40
Products: -
Products: -
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
Substrates: the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
Products: -
Products: -
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
Substrates: the enzyme cleaves the phosphocholine head group from platelet-activating factor
Products: -
Products: -
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
Substrates: the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
Products: -
Products: -
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
Substrates: the enzyme cleaves the phosphocholine head group from platelet-activating factor
Products: -
Products: -
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
Substrates: 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
Products: -
Products: -
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
Substrates: -
Products: -
Products: -
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
Substrates: 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
Products: -
Products: -
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
?
Substrates: the phosphatidylcholinesterase activity of the enzyme is five-fold higher than the sphingomyelinase C activity
Products: -
Products: -
?
sphingomyelin + H2O
?
Substrates: the phosphatidylcholinesterase activity of the enzyme is five-fold higher than the sphingomyelinase C activity
Products: -
Products: -
?
sphingomyelin + H2O
?
-
135146, 135147, 135148, 135149, 135150, 135153, 135156, 135159, 135160, 135161, 135168, 135169, 135187
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
?
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
-
Substrates: the enzyme is active towards sphingomyelin species with a range of fatty acid chain lengths (C16-C24)
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphorylcholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphorylcholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: hydrolysis of sphingomyelin dispersed in diheptanoylphosphatidyl-choline. Premicellar complexes of sphingomyelinase mediate enzyme exchange for the stationary phase turnover
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: SMase shows very low activity against condensed sphingomyelin, but is active on loosely organized sphingomyelin in bilayers and monolayers, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: the enzyme is important in the ceramide catabolism, overview
Products: -
Products: -
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Q4LEU0
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: very low activity in the absence of detergent
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: acid SMase is involved in colonic cancer development and apoptosis
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: degradation of sphingomyelin
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: nSMase2 uses sphingomyelin preferentially as a substrate in vitro with no activity against lyso-PAF
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
678250, 679604, 680754, 679144, 692236, 692274, 694111, 694201, 694260, 694284, 691060, 691456, 692009, 705457, 705473
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the enzyme is important in ceramide metabolism, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: SMase C causes hemolysis and thus is suspected to be a potential virulence factor
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: D-erythrosphingosine or dihydroxysphingosine configuration of sphingomyelin results in a 3-5fold faster hydrolysis in comparison to a D-threo or L-erythro configuration
Products: -
Products: -
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: erythro-isomers of DL-trans-2-N-palmitoyl-1-O-phosphorylcholinesphingosine or dihydrosphingosine hydrolyzed faster than the threo-isomer
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: DL-erythro-N-palmitoylsphingophosphorylcholine, N-stearylsphingophosphorylcholine, N-lignocerylsphingophosphorylcholine in monomolecular layers
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: 100% activity
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Streptomyces griseocarneus NBRC13471
Substrates: 100% activity
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
Substrates: 127fold higher activity than with sphingomyelin in the absence of detergent
Products: -
Products: -
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
Substrates: 980% of activity with sphingomyelin in the absence of detergent
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
Products: -
Products: -
?
additional information
?
-
Substrates: exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
Products: -
Products: -
?
additional information
?
-
Q4LEU0
Substrates: neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
Products: -
Products: -
?
additional information
?
-
Q4LEU0
Substrates: the enzyme has no activity against choline-methyl-phosphatidylcholine
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme has no activity against choline-methyl-phosphatidylcholine
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
Products: -
Products: -
?
additional information
?
-
-
Substrates: acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
Products: -
Products: -
?
additional information
?
-
-
Substrates: an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: ASM is necessary for stress-induced cell death
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with 4-nitrophenyl-TMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with 4-nitrophenyl-TMP
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with sphingomyelin or AMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with sphingomyelin or AMP
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme is a virulence factor
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is a virulence factor
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
Products: -
Products: -
?
additional information
?
-
Substrates: a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
Products: -
Products: -
?
additional information
?
-
-
Substrates: a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with AMP and diadenosine tetraphosphate
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with AMP and diadenosine tetraphosphate
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
Products: -
Products: -
?
additional information
?
-
-
Substrates: expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in sphingomyelin digestion
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is inactive towards sphingosine 1-phosphate and phosphatidylcholine
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
-
Substrates: low activity
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphorylcholine
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + choline phosphate
-
Substrates: -
Products: -
Products: -
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine, ceramide colocalizes with acetylated tubulin in primary cilia and the mitotic spindle of human embryonic stem cells
Products: 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
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Substrates: -
Products: a ceramide is an N-acylsphingosine
Products: a ceramide is an N-acylsphingosine
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
Substrates: the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
Products: -
Products: -
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
Substrates: the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
Products: -
Products: -
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
Substrates: 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
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Products: -
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
?
-
135146, 135147, 135148, 135149, 135150, 135153, 135156, 135159, 135160, 135161, 135168, 135169, 135187
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
?
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
ceramide + phosphocholine
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: the enzyme is important in the ceramide catabolism, overview
Products: -
Products: -
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
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Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: acid SMase is involved in colonic cancer development and apoptosis
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: degradation of sphingomyelin
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: the enzyme is important in ceramide metabolism, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: SMase C causes hemolysis and thus is suspected to be a potential virulence factor
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: 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
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: -
Products: -
Products: -
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Substrates: neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
Products: -
Products: -
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additional information
?
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Substrates: exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
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Products: -
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additional information
?
-
-
Substrates: SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
Products: -
Products: -
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additional information
?
-
Q4LEU0
Substrates: neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
Products: -
Products: -
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additional information
?
-
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Substrates: neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
Products: -
Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
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Products: -
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additional information
?
-
-
Substrates: acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
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Products: -
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additional information
?
-
-
Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
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Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
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additional information
?
-
-
Substrates: nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
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Products: -
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additional information
?
-
-
Substrates: an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
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Products: -
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additional information
?
-
-
Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
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Products: -
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additional information
?
-
-
Substrates: Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
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Products: -
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additional information
?
-
-
Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
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additional information
?
-
-
Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
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additional information
?
-
-
Substrates: a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
Products: -
Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: ASM is necessary for stress-induced cell death
Products: -
Products: -
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additional information
?
-
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Substrates: 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
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Products: -
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additional information
?
-
Substrates: the enzyme is a virulence factor
Products: -
Products: -
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additional information
?
-
-
Substrates: the enzyme is a virulence factor
Products: -
Products: -
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additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
Products: -
Products: -
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additional information
?
-
Substrates: a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
Products: -
Products: -
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additional information
?
-
-
Substrates: a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
Products: -
Products: -
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additional information
?
-
Substrates: 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
Products: -
Products: -
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additional information
?
-
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Substrates: 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
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Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
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additional information
?
-
-
Substrates: Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
Products: -
Products: -
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additional information
?
-
-
Substrates: 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
Products: -
Products: -
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additional information
?
-
-
Substrates: Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
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additional information
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Substrates: 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
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additional information
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Substrates: 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
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additional information
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Substrates: 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
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additional information
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Substrates: neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
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additional information
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Substrates: 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
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additional information
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Substrates: caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
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additional information
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Substrates: expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
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additional information
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Substrates: the enzyme is involved in sphingomyelin digestion
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additional information
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Substrates: 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
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additional information
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Substrates: Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
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additional information
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Substrates: 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
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additional information
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Substrates: 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
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additional information
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Substrates: 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
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additional information
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Substrates: 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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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
Cu2+
Fe2+
KCl
Mg2+
Mn2+
Sr2+
Zn2+
additional information
Ca2+
Km: 0.0191 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Ca2+
-
activated by micromolar concentrations of Ca2+ (0.0001 or 0.00001 mM) under Mg2+-free conditions, ceramide generation is dependent upon the calcium ionophore A23187, nSMase is not activated by Ca2+ cations in the presence of 1 mM Mg2+
Co2+
-
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
Co2+
Km: 0.142 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+. There are three distinct metal ion-binding sites in a long horizontal cleft across the bc-SMase molecule
Mg2+
-
two-step activation, high-affinity binding site with 50% saturation at 0.0041 mM, low-affinity-binding site with 50% saturation at 20 mM, approx. 5fold activation at 20 mM
Mg2+
-
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
Mg2+
-
the enzyme is a Mg2+-dependent neutral sphingomyelinase with two metal ion-binding sites in a long horizontal cleft across the molecule, with one Mg2+ in the central region of the cleft and one divalent metal ion at the side-edge of the cleft. The Mg2+ at the side-edge of the enzyme plays an important role in the binding to membranes
Mg2+
required by N-SMase for activity, residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
Mg2+
Km: 0.0161 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Mg2+
-
approx. 2fold activation of T-mSMase isoforms delta and gamma at 1 mM and 5 mM, respectively, both S-mSMase isoforms epsilon and zeta require 5 mM Mg2+ for maximal activity
Mg2+
required, high concentrations of up to 50 mM of Mn2+ stimulate enzyme activity
Mg2+
dependent on, isozyme Sph2 is unique and possesses the Mg2+-binding Glu53 residue in the metal-binding site
Mn2+
-
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
Mn2+
Km: 0.0149 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Mn2+
-
nSMase activity of the recombinant protein nSM1 increases 4.5fold in the presence of 0.5 mM Mn2+
Mn2+
required, low concentrations of Mn2+ stimulate enzyme activity
Mn2+
can replace Mg2+, maximal activation at 1-2 mM, slight inhibition above
Sr2+
Km: 0.018 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
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+
-
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+
zinc metalloenzyme, contains three essential Zn2+ in its N-terminal domain
Zn2+
-
Zn2+-dependent sphingomyelinase acid activity is much higher than Zn2+ independent isoform activity in both fetal and mother's blood
Zn2+
-
activates the alk-SMase activity with platelet-inactivating factor, mutation of the metal binding site abolishes the enzyme activity
Zn2+
-
aSMase is processed from a 75-kDa, Zn2+-activated proenzyme to a mature 65 kDa, Zn2+-independent L-SMase
Zn2+
-
activates the alk-SMase activity with platelet-inactivating factor, mutation of the metal binding site of alk-SMase abolishes the enzyme activity
additional information
-
Cu2+, Zn2+, and Ni2+ are unable to stimulate activity, nSMase is not activated by Ca2+ cations in the presence of 1 mM Mg2+
additional information
-
Mg2+, Mn2+, Ca2+ and Zn2+, or Ca2+ have no significant effect on the activity
additional information
Ca2+, Co2+, Fe2+, or Zn2+ do not support MA-nSMase activity
additional information
-
Ca2+, Co2+, Fe2+, or Zn2+ do not support MA-nSMase activity
additional information
the order of potency to enhance the activity is Zn2+>Mn2+>Cu2+>Fe2+
additional information
-
the order of potency to enhance the activity is Zn2+>Mn2+>Cu2+>Fe2+
additional information
not stimulated by Ca2+, CO2+, and Fe3+
additional information
central metal-binding site residues N77, E119, D265, N267, D374, and H375 are completely conserved in the enzyme
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1-aminodecane-1,1-diyl)bis(phosphonic acid)
-
a substrate analogue inhibitor of aSMase
(1S,2R,3R,4S,5S,6R)-3,5-bis([bis[(2-nitrophenyl)methoxy]phosphoryl]amino)-2,4,6-trihydroxycyclohexyl hexadecane-1-sulfonate
-
-
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
2,6-bis(cyclopentyloxy)-4-[5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
-
2,6-di-tert-butoxy-4-[5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
-
2,6-dimethoxy-4-[1-methyl-5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
-
27-Hydroxycholesterol
inhibition of acid sphingomyelinase; inhibition of neutral sphingomyelinase occurs at a posttranscriptional level
adenosine 5'-monophosphate
-
periodate-oxidized and an isomer with arabinose instead of ribose as sugar component
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
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
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
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
phenylmethylsulfonyl fluoride
70.3% residual activity at 2 mM
phosphatidyl inositol 3,5-bisphosphate
-
potent selective acid sphingomyelinase inhibitor
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
-
-
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
-
inhibits taurocholate-induced activation
ambroxol
-
i.e. trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol. Inhalation of ambroxol reduces acid sphingomyelinase activity in nasal epithelial cells and prevents pp-VSV-SARS-CoV-2 spike induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo
Ca2+
-
when sphingomyelin as substrate with Triton X-100 is used, competitive inhibitor against Mg2+
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
-
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
D609
-
48% inhibition of the enzyme in chromain after 30 min of treatment, no inhibition by D609 in the nuclear membrane
desipramine
-
inhibits the acid SMase, and lipopolysaccharide induction of interleukin-8 synthesis in vivo
EDTA
5 mM, complete inhibition, activity is comletely restored by the subsequent addition of 10 mM Mg2+ or Mn2+
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
GW4869
-
inhibits the neutral SMase, and lipopolysaccharide induction of interleukin-8 synthesis in vivo
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
scyphostatin
-
0.005 mM, 50% inhibition, complete inhibition at 0.033 mM
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
sphingomyelin
-
hydrolysis of platelet-activating factor; strong competitive inhibition of platelet-inactivating factor hydrolysis
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
-
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
-
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+
-
nSMase activity of the recombinant protein nSM1 abolishes (12% residual activity) by 5 mM Zn2+
Zn2+
high millimolar Zn2+ concentration leads to inhibition of enzyme activity
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
-
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
-
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
-
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
-
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
an allosteric cavity in nSMase2 has been identified that can be exploited for the development of new inhibitors with anti-flaviviral activity
-
additional information
-
vacuole maturation, replication, and infectious progeny generation by Anaplasma phagocytophilum, which exclusively hijacks low-density lipoprotein cholesterol, are halted and Coxiella burnetii, for which lysosomal cholesterol accumulation is bactericidal, is killed by functional inhibitors of acid sphingomyelinase
-
additional information
-
functional inhibitors of acid sphingomyelinase have the potential to inhibit the lysosomal acid sphingomyelinase, and therefore disrupt the entry of viruses into cells
-
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
-
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
-
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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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
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
choline
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
galectin-I
-
human, induces apoptosis and initiates the acid SMase-mediated release of ceramide
-
H2O2
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, overview
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-specific phospholipase C
-
increases the N-SMase activity up to 2fold
-
protein kinase C-zeta
-
mediates the activation of N-SMase by 1,25-dihydroxyvitamin D3, while protein kinase C-delta inhibits the activation
-
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
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
-
bile salt
-
dependent on, particularly taurocholate and taurochenodeoxycholate
cardiolipin
-
anionic phospholipids required for activity, maximal activation at 1 mM, 21% of activation with phosphatidylserine
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
phosphatidic acid
-
anionic phospholipids required for activity, maximal activation at 1 mM, 33% of activation with phosphatidylserine
phosphatidylethanolamine
-
sphingomyelinase is enhanced by cholesterol and by lipids with an intrinsic negative curvature, e.g. phosphatidylethanolamine
phosphatidylglycerol
-
anionic phospholipids required for activity, maximal activation at 1 mM, 79% of activation with phosphatidylserine
phosphatidylinositol
-
anionic phospholipids required for activity, maximal activation at 1 mM, 53% of activation with phosphatidylserine
phosphatidylserine
-
0.2 mM, approx. 108fold activation of sphingomyelin hydrolysis in the presence of 0.1% Triton X-100
phosphatidylserine
-
nSMase2 has low basal activity, it is fully activated by phosphatidylserine. The juxtamembrane linker in neutral sphingomyelinase-2 functions as an intramolecular allosteric switch that activates the enzyme
phosphatidylserine
-
anionic phospholipids required for activity, maximal activation at 1 mM
sodium deoxycholate
-
4.4fold activation of S-mSMase epsilon at 2 mM, 4.7fold activation of S-mSMase zeta at 1 mM
taurochenodeoxycholate
-
strong activation, maximal activation at approx. 2 mM
taurochenodeoxycholate
-
stimulates hydrolysis of sphingomyelin and platelet-activating factor
taurocholate
-
the enzyme activity is specifically stimulated by 6 mM taurocholate
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
-
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
205% relative activity at 0.1% (v/v) Triton X-100
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
Q4LEU0
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
-
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
-
activation of acid sphingomyelinase by gemcitabine or doxorubicin, respectively, via reactive oxygen species
-
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
-
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
-
secretory sphingomyelinase is upregulated in chronic heart failure
-
additional information
-
1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine induces neutral sphingomyelinase activity
-
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
-
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
-
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
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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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.06
BODIPYFL-C12-sphingomyelin
-
pH and temperature not specified in the publication
-
0.034
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine
-
in presence of Mg2+
12.6
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine
-
at pH 7.0 and 40°C
39.6
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine
-
at pH 7.0 and 40°C
0.027
sphingomyelin
37°C, pH 7.4, recombinant nSMase2 in yeast microsomes
additional information
additional information
-
different SMase kinetic steps are differentially regulated by non-substrate lipids, overview
-
additional information
sphingomyelin
-
comparison of values from enzymes of normal and mutated tissues
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0033
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine
-
at pH 7.0 and 40°C
0.0103
4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine
-
at pH 7.0 and 40°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0052
N-[(2S,3R,4E)-1-(2,2'-bipyridin-6-ylmethoxy)-3-hydroxyoctadec-4-en-2-yl]hexanamide [Mg2+]
-
pH and temperature not specified in the publication
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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
0.00012
2,6-bis(cyclopentyloxy)-4-[5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
Homo sapiens
pH and temperature not specified in the publication
0.00052
2,6-di-tert-butoxy-4-[5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
Homo sapiens
pH and temperature not specified in the publication
0.04
2,6-dimethoxy-4-[1-methyl-5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
Homo sapiens
pH and temperature not specified in the publication
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
0.0012
N-[(2S,3R,4E)-1-(2,2'-bipyridin-6-ylmethoxy)-3-hydroxyoctadec-4-en-2-yl]hexanamide [Mg2+]
Bacillus cereus
-
pH and temperature not specified in the publication
0.00093
phosphatidyl inositol 3,5-bisphosphate
Rattus norvegicus
-
in 100 mM NaOAc, pH 5.2, at 37°C
0.00135
2,6-dimethoxy-4-[5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol
Homo sapiens
wild-type enzyme, pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000000025
Q4LEU0
recombinant enzyme, using (1-O-octadecyl-9,10-)lyso-platelet-activating factor as substrate, in 100 mM Tris-HCl, pH 7.5, 5 mM dithiothreitol, 5 mM MgCl2, at 37°C
0.0000264
Q4LEU0
wild type enzyme, using C6-7-nitro-2-1,3-benzoxadiazol-4-yl-sphingomyelin as substrate, in 100 mM Tris-HCl, pH 7.5, 5 mM dithiothreitol, 5 mM MgCl2, at 37°C
0.0000427
Q4LEU0
wild type enzyme after heat shock for 1 h at 37°C, using C6-7-nitro-2-1,3-benzoxadiazol-4-yl-sphingomyelin as substrate, in 100 mM Tris-HCl, pH 7.5, 5 mM dithiothreitol, 5 mM MgCl2, at 37°C
0.0000542
Q4LEU0
wild type enzyme after heat shock for 1 h at 38°C, using C6-7-nitro-2-1,3-benzoxadiazol-4-yl-sphingomyelin as substrate, in 100 mM Tris-HCl, pH 7.5, 5 mM dithiothreitol, 5 mM MgCl2, at 37°C
0.13
0.246
culture supernatant, in 50 mM glycine-NaOH buffer (pH 9.6), at 37°C
92.8
-
5fold higher specific activity of rhASM purified from CHO cell-harvests stored at -20°C
98.4
400fold purified enzyme, in 50 mM glycine-NaOH buffer (pH 9.0), at 55°C
additional information
0.13
-
with 4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine as substrate, at pH 7.0 and 40°C
0.13
-
with 4-(4-nitrophenoxy)-2-hydroxy-butyl-1-phosphorylcholine as substrate, at pH 7.0 and 40°C
additional information
-
quantitative expression analysis in articular chondrocytes
additional information
quantitative expression analysis in articular chondrocytes
additional information
-
activity of Alk-SMase and correlation to neutral ceramidase in meconium of different gestational ages, overview
additional information
-
measurement of transepithelial permeability and transepithelial resistance in Caco-2 cells, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 5
4.5
5 - 5.5
5 - 6
5.5
6.5
7 - 8
7.2
7.4
7.5
additional information
7.5
Q4LEU0
recombinant neutral SMase 1 hydrolyzes choline-methyl-sphingomyelin optimally at pH 7.5 in the presence of an Mg2+ ion
additional information
the enzyme is activated by the low gut pH
additional information
the enzyme is activated by the low gut pH
additional information
the enzyme is activated by the low gut pH
additional information
the enzyme is activated by the low gut pH
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.5 - 6.5
4.5 - 10
-
T-mSMase alpha, approx. 50% of maximal activity at pH 4.5, T-mSMase isoforms beta, gamma and delta, approx. 25% of maximal activity at pH 4.5, T-mSMase isoforms alpha, beta, gamma and delta, almost no activity at pH 10.0
4.5 - 9
approx. 5% of maximal activity at pH 4.5, approx. 15% of maximal activity at pH 9.0
5 - 10
5 - 8
5.5 - 8.4
-
approx. 25% of maximal actiity at pH 6.0, approx. 75% of maximal activity at pH 8.0
5.5 - 9
-
less than 5% of maximal activity at pH 5.5 and pH 9.0, respectively
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 - 10.5
6 - 8.5
-
approx. 10% of maximal activity at pH 6.0 and pH 8.5, respectively
6 - 9
6.5 - 9.5
-
approx. 25% of maximal activity at pH 6.5, approx. 55% of maximal activity at pH 9.5
7 - 10
-
the activity of Alk-SMase expressed from the yeast has a similar pH dependency, being low at acid pH, increasing after 7 and optimal at 9.0
7.5
the enzyme shows 50% activity at pH 7.5 and 80% activity at pH 9.0
additional information
6 - 9
-
approx. 30% of maximal activity at pH 6.5, approx. 70% of maximal activity at pH 9.0
6 - 9
-
pH 6.0: about 55% of maximal activity, pH 9.0: about 35% of maximal activity, hydrolysis of platelet-activating factor
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
-
assay at
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
27 - 40
the enzyme shows more than 60% activity between 27 and 40°C, and about 40% activity at 45°C
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
serovar Lai, gene sph2 or LA_1029 encoding isozyme Sph2
UniProt
brenda
serovar Lai, gene sph2 or LA_1029 encoding isozyme Sph2
UniProt
brenda
-
-
-
brenda
-
-
-
brenda
-
135146, 135147, 135148, 135149, 135150, 135152, 135153, 135154, 135156, 135159, 135160, 135161, 135164, 135168, 135169, 135176, 135178, 135179, 135180, 135184, 135185, 135187
-
-
brenda
-
-
-
brenda
-
666964, 677601, 677818, 677875, 678939, 679144, 679649, 679682, 679685, 680745, 680767, 681259, 681266, 681322, 681494, 682246, 682477, 682983, 691060, 691456, 692009, 692236, 692274, 694111, 694201, 694260, 694284, 705457, 705473, 714689, 715614, 715641, 716445, 729101, 730294, 730356, 750264, 750265
-
-
brenda
acid sphingomyelinase, splicing forms ASM-1 to ASM-4; gene SMPD1
UniProt
brenda
haSMase deficiency due to mutations in haSMase gene leads to Niemann-Pick disease, an autosomal recessive sphingolipidosis
-
-
brenda
one form of Niemann-Pick disease is caused by a deficiency of acid sphingomyelinase
-
-
brenda
-
135155, 135163, 135165, 135170, 135171, 135172, 135173, 135174, 135175, 135177, 135183, 650323, 651315
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma
brenda
-
isolated from bone marrow or peritoneal lavage of gene-targeted mice lacking Asm and their wild-type littermates
brenda
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
brenda
-
acid-SMase activity is comparable in lung and intestine
brenda
additional information
-
umbilical cord blood. Zn2+-dependent sphingomyelinase acid activity is much higher than Zn2+ independent isoform activity in both fetal and mother's blood
brenda
-
a secreted, zinc-activated form of ASM is found in the plasma which plays an important role in the development of atherosclerosis
brenda
-
in hippocampus the enzyme activity is significantly higher than in striatum and cortex. Significant increase in cortical membrane-associated N-Sase activity with age
brenda
-
in hippocampus the enzyme activity is significantly higher than in striatum and cortex. Significant increase in cortical membrane-associated N-Sase activity with age
-
brenda
-
cerebrospinal fluid contains a detectable level of secretory enzyme, which is unrelated to serum enzyme activity, no influence of sex or age on enzyme activity in cerebrospinal fluid
brenda
-
cerebrospinal fluid contains a detectable level of secretory enzyme, which is unrelated to serum enzyme activity, no influence of sex or age on enzyme activity in cerebrospinal fluid
brenda
-
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
brenda
-
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
-
brenda
-
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
brenda
-
unchanged A-SMase activity in the outer epidermis of chronologically aged skin, in the lower epidermis the activity is reduced
brenda
-
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
brenda
expression analysis of alkaline sphingomyelinase forms, overview
brenda
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
brenda
-
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
brenda
-
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
-
brenda
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma
brenda
-
exclusively expressed in intestine, lack of bSMase may be related to colon carcinogenesis
brenda
-
acid-SMase activity is comparable in lung and intestine, alk-ASMase activity is lower in lung than in intestine
brenda
-
endogenous nSMase2 mRNA is upregulated 5fold when MCF-7 cells become growth-arrested at confluence, and total neutral SMase is increased 119% with respect to subconfluent cells
brenda
-
-
brenda
-
from cord blood of infants of 30-40 weeks, of adults from normal healthy volunteers of either sex, from patients with Padgetis disease
brenda
-
total neutral sphingomyelinase activity does not differ between muscle types. nSMase2 content is detectable in all muscles and higher in extensor digitorum longus, soleus, and plantaris compared to diaphragm whereas nSMase3 is undetectable in all muscles
brenda
additional information
-
expression of the enzyme in different human tissues
brenda
additional information
-
Alk-SMase developmental enzyme activity, overview, Alk-SMase activity decreases with age
brenda
additional information
ubiquitous tissue distribution of enzyme, distribution of splicing forms, overview
brenda
additional information
ubiquitous tissue distribution of enzyme, distribution of splicing forms, overview
brenda
additional information
ubiquitous tissue distribution of enzyme, distribution of splicing forms, overview
brenda
additional information
ubiquitous tissue distribution of enzyme, distribution of splicing forms, overview
brenda
additional information
-
ubiquitous tissue distribution of enzyme, distribution of splicing forms, overview
brenda
additional information
-
Alk-SMase developmental enzyme activity, overview, Alk-SMase activity decreases with age
brenda
additional information
-
no detectable activity of acid-SMase in colonic mucosa
brenda
additional information
-
maximum activity in the distal jejunum, little activity in bile, liver, pancreas after trypsin treatment
brenda
additional information
-
Alk-SMase developmental enzyme activity, overview, Alk-SMase activity decreases with age
brenda
additional information
-
age-related increase in the activity of NSMase-2
brenda
additional information
-
immunolocalization study of Mg2+-dependent neutral sphingomyelinase, overview
brenda
additional information
-
immunolocalization study of Mg2+-dependent neutral sphingomyelinase, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
neutral sphingomyelinase is concentrated at the endothelial cell surface in caveolae
brenda
-
the ratio of secreted to intracellular activity is about 8fold greater in I-cells (skin fibroblasts from I-cell disease patients, in which one of the enzymes responsible for mannose phosphorylation, GlcNAc-phosphotransferase, is deficient) than in normal cells
brenda
additional information
-
neutral sphingomyelinase is concentrated at the endothelial cell surface in caveolae
brenda
-
age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
brenda
-
age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
-
brenda
Q4LEU0
in the case of HEK293 transfectants, the zebrafish SMase 1 is also colocalized in both the Golgi apparatus and the endoplasmic reticulum
brenda
NSM-1 mainly resides in the nucleus and endoplasmic reticulum
brenda
-
extracellular soluble toxin that induces hemolysis by acting on sphingomyelin-rich erythrocytes of mammals such as ruminants
-
brenda
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
brenda
-
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
-
brenda
-
secretory sphingomyelinase S-SMase is secreted by endothelial cells upon stimulation with lipopolysaccharides and pro-inflammatory cytokines such as TNF-alpha
-
brenda
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
brenda
-
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
-
brenda
-
secreted enzyme, infection of macrophages with Salmonella enterica serovar typhimurium stimulates extracellular ASM secretion
-
brenda
-
in Pseudomonas aeruginosa, the enzyme is co-expressed with the 17 kDa chaperone PlcR2 and is secreted as the fully folded heterodimer PlcHR2, about 95 kDa, by the twin arginine translocase via the cytoplasmic membrane and through the outer membrane, by the Xcp TypeII secretory system
-
brenda
-
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
brenda
Q4LEU0
SMase 1 is also localized in the Golgi apparatus
brenda
-
translocation of ASMase from endolysosomes to the plasma membrane after sustained phorbol 12-myristate 13-acetate treatment
brenda
-
inner lysosomal membrane, detachment caused by weak bases inhibits the enzyme
brenda
-
inner lysosomal membrane, detachment caused by weak bases inhibits the enzyme
brenda
-
can rapidly move from lysosomes to cell surface upon stimulation by cytokines and other factors
brenda
-
lysosomal acid sphingomyelinase is transported to the endosomal compartment and anchored to the inner lysosomal membrane
brenda
nSMase1 contains two putative transmembrane domains at the C-terminus
brenda
-
catalytic region of nSMase2 localizes to the cytosolic side of the plasma membrane, proposed membrane topology model, overview
brenda
-
phosphorylation of a specific serine residue on ASM (S508) by protein kinase C-delta is required for its translocation to the cell surface
brenda
-
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
brenda
-
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
-
brenda
Q4LEU0
in zebrafish embryonic cells, the endogenous SMase enzyme is localized in the microsomal fraction
-
brenda
NSM-1 mainly resides in the nucleus and endoplasmic reticulum
brenda
-
nSMase2 is nearly exclusively located at the plasma membrane in confluent, contact-inhibited cells
brenda
nSMase1 contains two putative transmembrane domains at the C-terminus
brenda
-
translocation of ASMase from endolysosomes to the plasma membrane after sustained phorbol 12-myristate 13-acetate treatment
brenda
-
nSMase2 translocates acutely to the plasma membrane of A549 epithelial cells in response to tumor necrosis factor alpha, regulated by p38-alpha MAPK
brenda
-
phorbol 12-myristate 13-acetate induces nSMase2 translocation to the plasma membrane in a time- and dose-dependent manner, rottlerin inhibits nSMase2 translocation in response to tumor necrosis factor and phorbol 12-myristate 13-acetate
brenda
-
membrane damage or the interaction with some bacterial and viral pathogens can trigger the enzyme's recruitment to the plasma membrane
brenda
-
secretory acid sphingomyelinase is transported to the outer leaflet of the plasma membrane
brenda
-
localizes to the outer leaflet of the plasma membrane
brenda
-
activated acid sphingomyelinase moves to plasma membrane outer leaflet
brenda
-
associated via anionic phospholipids binding sites at the enzyme's N-terminus
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview. aSMase1 is regulated and expressed in a pregnancy and milk gland-specific manner
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview. aSMase1 is regulated and expressed in a pregnancy and milk gland-specific manner
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview. aSMase1 is regulated and expressed in a pregnancy and milk gland-specific manner
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview. aSMase1 is regulated and expressed in a pregnancy and milk gland-specific manner
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview
-
brenda
additional information
immunolocalization and quantitative realtime PCR expression analysis, overview
-
brenda
additional information
-
nSMase2 is distributed thoughout the cells in subconfluent, proliferating cultures
-
brenda
additional information
C-terminal region of nSMase2 harbors several motifs that may play a role in its localization
-
brenda
additional information
C-terminal region of nSMase2 harbors several motifs that may play a role in its localization
-
brenda
additional information
-
the processed mature enzyme one portion of this enzyme is transported to the lysosomes and a second portion is secreted to extracytosolic side of the plasma membrane
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brenda
Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
metabolism
physiological function
additional information
drug target
-
aSMase/ceramide pathway may be a potential target for the treatment of vascular dysfunction in diabetes mellitus
drug target
-
functional inhibition of acid sphingomyelinase is a potential host-directed therapy for diseases caused by pathogens that manipulate low-density lipoprotein cholesterol
drug target
-
functional inhibitors of acid sphingomyelinase have the potential to inhibit the lysosomal acid sphingomyelinase, and therefore disrupt the entry of viruses into cells
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 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 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
-
loss of nSMase activity leads to a Big-Eye-like phenotype, and affect s protein trafficking, as well as VSG trafficking, overview
malfunction
-
deficiency of the enzyme leads to lysosomal accumulation of sphingomyelin resulting in in Niemann-Pick types A and B diseases
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
-
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
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
-
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
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
-
enzyme inhibition blocks T-helper cell responses. Enzyme knockdown dampens CD3/CD28 signals and broadly inhibits T-helper cell responses
malfunction
-
acid sphingomyelinase inhibition causes cellular sphingomyelin accumulation, which induces cancer cell death specifically in hypoxic tumor spheroids
malfunction
-
enzyme knockdown reduces Clostridium botulinum C2 toxin-induced cell rounding
malfunction
-
wild-type mice rapidly control Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection, while Asm-/- mice fail to control the infection and kill the bacteria
malfunction
-
the absence of the enzyme (NSM2) promotes a hyperactive metabolic state in unstimulated CD4+ T cells yet fails to support sustained T cell responses upon antigenic stimulation
malfunction
Niemann Pick disease is caused by acid sphingomyelinase deficiency (an SMPD1 gene mutation), which leads to organ dysfunction due to the accumulation of sphingomyelin in various organs
malfunction
-
Anaplasma phagocytophilum fails to productively infect acid sphingomyelinase knockout mice (ASM-/-)
malfunction
-
treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
-
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
-
the essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei
metabolism
-
interaction in the NO/NOS and SMases/ceramide signaling pathways, overview
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
-
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
-
all-trans-retinoic acid regulation of nSMase2, 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
-
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
-
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
-
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
-
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
-
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
-
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
the recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
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
-
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
-
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
-
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
-
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 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
-
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
-
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
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
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
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
the enzyme acts as a negative regulator of innate immune signaling, affecting cellular lipid composition and membrane fluidity
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
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the enzyme mediates T-cell proliferation after anti-CD3/CD28 antibody stimulation and alters CD4+ T-cell activation signals by generating ceramide
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
-
Clostridium botulinum C2 toxin requires acid sphingomyelinase activity during internalization into cells
physiological function
the enzyme is important in various physiological and pathological processes, such as apoptosis, regulation of immune cell function and release of inflammatory factors
physiological function
-
the enzyme plays an important role in endothelial dysfunction. aSMase/ceramide accumulation impairs eNOS/NO pathway and endothelial dysfunction in high glucose condition or diabetes
physiological function
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the enzyme controls dopamine activity and responses to appetitive stimuli in mice. It is one of the main enzymes involved in ceramide synthesis, in the molecular control of monoaminergic systems in their basal activity and in response to pharmacological and natural reinforcers
physiological function
-
the enzyme contributes to the control of Mycobacterial infection via a signaling cascade leading from reactive oxygen species to cathepsin D. Infection of wild-type macrophages results in activation of Asm
physiological function
role of the bacterial enzyme in pathogenesis. The enzyme (LmPlcB) is activated when Listeria monocytogenes reaches the acidic environment of late endosomes-lysosomes, aiding bacterial escape toward the cytosol and cell-to cell propagation
physiological function
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neutral sphingomyelinase-2 controls T cell metabolic homeostasis and reprogramming during activation
physiological function
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the enzyme could serve as a future biomarker or therapeutic target in diseases affected by sphingolipid derangements
physiological function
neutral sphingomyelinase 2 is involved in lipid metabolism and plays a key role in West Nile virus (WNV) and Zika virus (ZIKV) infection
physiological function
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the enzyme influences low-density lipoprotein cholesterol egress from the lysosome. It is a key enzyme for infection cycles of vacuole-adapted bacteria that target cholesterol trafficking (Anaplasma phagocytophilum, Coxiella burnetii, Chlamydia trachomatis, and Chlamydia pneumoniae)
physiological function
-
acid sphingomyelinase and ceramide play a prominent role in receptor signaling and infection cycle
physiological function
-
the enzyme produces the bioactive lipid ceramide and has important roles in neurodegeneration, cancer, and exosome formation
physiological function
-
the enzyme catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. It is a regulator of canonical transient receptor potential channel 6 (TRPC6) activity
physiological function
-
neutral sphingomyelinase associated with subsarcolemmal mitochondria may play a role in intracellular signalling processes involving ceramides in skeletal muscle and nSMase2 may be the key isoform, specifically in slow twitch muscle like soleus
physiological function
-
sphingomyelinase catalyzes ceramide production from sphingomyelin. Ceramides are critical in cellular responses such as apoptosis. They enhance mitochondrial outer membrane permeabilization through selfassembly in the mitochondrial outer membrane to form channels that release cytochrome c from intermembrane space into the cytosol, triggering caspase-9 activation. Mitochondrial Mg2+-independent (SMasemt-iSMase) may play a critical role in generating ceramides for mitochondrial outer membrane permeabilization, cytochrome c release, and apoptosis
physiological function
the enzyme plays an important role in T lymphocyte activation, in many diseases such as tumors, Alzheimer's disease and cardiovascular diseases. It can promote inflammation by participating in the release of inflammatory factors and the production of chemokines. The enzyme mediates bleomycin-induced pulmonary fibrosis
physiological function
role of the bacterial enzyme in pathogenesis. When Clostridium perfringens reaches a certain density in soft tissues and the enzyme (CpPLC) is produced, this toxin induces endothelial damage and platelet aggregation, which favors ischemia, thus providing an optimal environment for bacterial growth
physiological function
-
the enzyme influences low-density lipoprotein cholesterol egress from the lysosome. It is a key enzyme for infection cycles of vacuole-adapted bacteria that target cholesterol trafficking (Anaplasma phagocytophilum, Coxiella burnetii, Chlamydia trachomatis, and Chlamydia pneumoniae)
physiological function
role of the bacterial enzyme in pathogenesis. PaPlcH secreted by Pseudomonas aeruginosa, hydrolyzes target phospholipids where the infection is being established, helps bacteria to obtain substrates from the host, and triggers signaling pathways that lead to inflammation
physiological function
-
role of the bacterial enzyme in pathogenesis. When Clostridium perfringens reaches a certain density in soft tissues and the enzyme (CpPLC) is produced, this toxin induces endothelial damage and platelet aggregation, which favors ischemia, thus providing an optimal environment for bacterial growth
-
physiological function
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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
-
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
-
role of the bacterial enzyme in pathogenesis. PaPlcH secreted by Pseudomonas aeruginosa, hydrolyzes target phospholipids where the infection is being established, helps bacteria to obtain substrates from the host, and triggers signaling pathways that lead to inflammation
-
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
-
additional information
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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
-
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
-
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
-
besides the aSMase, an alkaline sphingomyelinase and two neutral sphingomyelinases 1 and 2, nSMase1 and nSMase2, exist
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
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
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
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the enhancement of alpha-hemolysis of Staphylococcus aureus could occur through the interaction of Staphylococcus aureus-sphingomyelinase and CAMP-like factors secreted from Aspergillus icronesiensis
additional information
-
the enhancement of alpha-hemolysis of Staphylococcus aureus could occur through the interaction of Staphylococcus aureus-sphingomyelinase and CAMP-like factors secreted from Aspergillus icronesiensis
-
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
-
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
-
Show AA Sequence and Transmembrane Helices (5635 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
150000
200000
33000
34000
37000
40000
42000
45000
46000
-
x * 97000 + x * 46000, the 46000 Da subunit may also be a degradation product
46900
Q4LEU0
recombinant enzyme, putative molecular weight calculated from amino acid sequence and on SDS-PAGE
47500
47600
53000
-
1 * 92000 + 1 * 53000, Western blotting analysis and activity gel analysis
60000
68000
70000
71000
72000
74000
75000
78386
-
2 * 78386, unmodified enzyme, mass spectrometry, 2 * 78500, about, SDS-PAGE, three-dimensional structure analysis of dimeric enzyme
78500
-
2 * 78386, unmodified enzyme, mass spectrometry, 2 * 78500, about, SDS-PAGE, three-dimensional structure analysis of dimeric enzyme
92000
-
1 * 92000 + 1 * 53000, Western blotting analysis and activity gel analysis
95000
97000
60000
-
x * 75000 with SDS-PAGE and western blotting analysis, x * 60000 than deglycosylated
70000
-
x * 71000, N-SMase2, SDS-PAGE, x * 70000, mature A-SMase, SDS-PAGE, x * 75000, pre-pro-form of A-SMase, SDS-PAGE
71000
-
x * 71000, N-SMase2, SDS-PAGE, x * 70000, mature A-SMase, SDS-PAGE, x * 75000, pre-pro-form of A-SMase, SDS-PAGE
75000
-
x * 75000 with SDS-PAGE and western blotting analysis, x * 60000 than deglycosylated
75000
-
x * 71000, N-SMase2, SDS-PAGE, x * 70000, mature A-SMase, SDS-PAGE, x * 75000, pre-pro-form of A-SMase, SDS-PAGE
97000
-
x * 97000 + x * 46000, the 46000 Da subunit may also be a degradation product
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
trimer
additional information
?
-
x * 75000 with SDS-PAGE and western blotting analysis, x * 60000 than deglycosylated
?
-
x * 71000, N-SMase2, SDS-PAGE, x * 70000, mature A-SMase, SDS-PAGE, x * 75000, pre-pro-form of A-SMase, SDS-PAGE
dimer
-
1 * 92000 + 1 * 53000, Western blotting analysis and activity gel analysis
dimer
-
2 * 78386, unmodified enzyme, mass spectrometry, 2 * 78500, about, SDS-PAGE, three-dimensional structure analysis of dimeric enzyme
additional information
-
the enzyme structure and topology influences the enzyme activity, overview
additional information
-
the enzyme contains the central site (catalytic site), side-edge site (membrane binding site), and beta-hairpin region (membrane binding site)
additional information
-
the enzyme contains the central site (catalytic site), side-edge site (membrane binding site), and beta-hairpin region (membrane binding site)
-
additional information
-
structural-functional properties of its carboxyl-terminus, amino acids 462-629, overview, ASM consists of a signal peptide, amino acids 1-46, in the N-terminal region, a small transmembrane domain, amino acids 25-47, a saposin B region, amino acids 87-165, that serves as an activator of various lysosomal lipid-degrading enzymes, a proline-rich region, amino acids 179-197, followed by the metallophosphoesterase catalytic domain, amino acids 199-461
additional information
the enzyme exists as both monomers and multimers that are associated with high and low enzymatic activity, respectively. Several oxidant-sensitive cysteine residues of the C-terminal catalytic domain are involved in enzyme oligomerization, but cysteines in the non-catalytic region of the enzyme (i.e. amino acids 1 to 337), as well as Cys359, Cys392, Cys420, Cys425, and Cys457 in the beginning of the catalytic domain, do not participate in oligomerization. Thioredoxin-mediated reduction of enzyme multimers to monomers
additional information
-
the enzyme exists as both monomers and multimers that are associated with high and low enzymatic activity, respectively. Several oxidant-sensitive cysteine residues of the C-terminal catalytic domain are involved in enzyme oligomerization, but cysteines in the non-catalytic region of the enzyme (i.e. amino acids 1 to 337), as well as Cys359, Cys392, Cys420, Cys425, and Cys457 in the beginning of the catalytic domain, do not participate in oligomerization. Thioredoxin-mediated reduction of enzyme multimers to monomers
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
lipoprotein
-
neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues, palmitoylation of nSMase2 via thioester linkage, mutational analysis, overview
no glycoprotein
phosphoprotein
proteolytic modification
additional information
glycoprotein
-
the five potential N-glycosylation sites are all glycosylated, activity of the enzyme is severely affected by defective N-glycosylation
glycoprotein
-
the mature form and its precursors have six potential N-glycosylation sites, and at least five of them are important for proper folding, protection against proteolysis, and enzymatic activity of A-SMase. A-SMase has a mannose 6-phosphate residue that is required for lysosomal targetting of the enzyme via the mannose 6-phosphate receptor
glycoprotein
-
synthesis of a 78 kDA preproform of the enzyme which is glycosylated and proteolytically cleaved to a 72 kDa pre-form and subsequently to a 70 kDA mature enzyme
glycoprotein
aSMase is an N-glycoprotein bearing 5 discrete asparagine-linked glycans with glycosylation of N395 and N520 being critical for normal secretion and function. SMPDL3A contains 7 potential N-linked glycosylation motifs (defined by the pattern NX[S|T], where X is any amino acid except proline). Notably, two of these motifs (N222 and N356) are perfectly aligned with the functionally important N395 and N520 N-linked sites of aSMase
glycoprotein
lysosomal acid sphingomyelinase (L-ASM) is glycosylated by high mannose oligosaccharides during Golgi transport. Secreted acid sphingomyelinase (S-ASM) has a more complex glycosylation pattern during Golgi transport than L-ASM
phosphoprotein
-
mannose phosphorylation is important in the trafficking of this enzyme
phosphoprotein
-
acid sphingomyelinase is activated by protein kinase Cdelta phosphorylation at Ser508, which is mediated by phorbol 12-myristate 13-acetate, overview
phosphoprotein
NSM-2 has phosphorylation sites in the N-terminus and C-terminus
proteolytic modification
-
the 75-kDa pre-proform of A-SMase, which is a pre-polypeptide with little if any enzymatic activity in the endoplasmic reticulum, is cleaved to an intermediate pro-form of 72 kDa, and further to the mature enzyme of 70 kDa in the lysosomes
proteolytic modification
-
synthesis of a 78 kDA preproform of the enzyme which is glycosylated and proteolytically cleaved to a 72 kDa pre-form and subsequently to a 70 kDA mature enzyme
proteolytic modification
-
aSMase is processed from a 75-kDa, Zn2+-activated proenzyme to a mature 65 kDa, Zn2+-independent L-SMase, C-terminal proteolytic processing
additional information
-
steady-state levels of ubiquitination are minimal for the wild-type ASM
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, crystal structures of Bc-SMase complexed to the functional metal ions Mg2+, Co2+, or Ca2+ are determined at 1.8 A, 1.8 A, and 1.4 A resolution, respectively
nSMase, crystal structure of nSMase complexed with Ca2+, Co2+, or Mg2+, and structure-function analysis
purified recombinant mutant N57A enzyme, hanging drop vapor diffusion method, mixing of 0.002 ml of 10 mg/ml protein in 20 mM Tris-HCl, pH7.0, with 0.002 ml of reservoir solution containing 18% w/v PEG 8000, 0.2 M MgCl2, and 0.1 M sodium cacodylate, pH 6.5, 4°C, X-ray diffraction structure determination and analysis at 2.4 A resolution
-
catalytic domain in complex with CMP, sitting drop vapor diffusion method, using 2.08 M disodium malonate pH 5, 0.23 M sodium thiocyanate
in complex with phosphocholine, hanging drop vapor diffusion method, using 20% (w/v) PEG 3350 as precipitant
vapor diffusion method, using 0.2 M sodium acetate, 20% (w/v) polyethylene glycol 8000, 0.1 M sodium cacodylate, pH 6.0
hanging-drop vapour-diffusion method, single crystals with dimensions 0.2 * 0.2 * 0.4 mm are obtained, diffraction data are collected to 1.8 A under cryogenic conditions, space group P6 with unit-cell parameters a = b = 140.6 A, c = 113.6 A
-
apo-enzyme and in complex with phosphorylcholine, hanging drop vapor diffusion method, using 0.2 M NH4NO3 and 25% (w/v) PEG 3350
sitting drop vapor diffusion method, using 0.2M lithium acetate and 20% (w/v) PEG 3350
purified wild-type enzyme and L-selenomethionine-labeled enzyme, mixing of 0.002 ml of 1.5 mg/ml protein in 50 mM Tris, pH 7.4, 50 mM NaCl, and 0.1 mM TCEP, with 700 nl of reservoir solution containing 10% dioxane, 0.1 M MES, pH 6.75 and 1.5 M ammonium sulfate, and 300 nl 0f 300 mM zwittergent solution, for the labeled enzyme, a protein solution at 9 mg/ml in 50 mM Tris, pH 7.4, 50 mM NaCl, and 0.1 mM TCEP is used, X-ray diffraction structure determination and analysis at 4.0 A and 2.75 A resolution, respectively, molecular replacement
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
F285A
F55A
-
site-directed mutagenesis, the mutation in close proximity to Mg2+ at the side-edge does not affect the enzyme
H151A
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
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
-
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
-
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
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
C629S
-
5fold increase in activity, modification or deletion of the thiol group on the C-terminal cysteine leads to activation of rhASM
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
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
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
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
H463A
2,6-dimethoxy-4-[5-phenyl-4-(thiophen-2-yl)-1H-imidazol-2-yl]phenol shows an IC50 value of 0.00135 mM against wild-type enzyme nSMase2 and 0.00322 mM against H463A mutant enzyme
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
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
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
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
Y537H
-
naturally occuring mutation, the mutant has severely defective enzymatic function
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
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
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
additional information
E53A
-
no sphingomyelin hydrolyzing and no hemolytic activity, E53 acts as an indespensable ligand of Mg2+ essential for catalytic activity
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
-
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
mutation of the two histidines, His134 and His252, abolished enzyme activity
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
-
acid sphingomyelinase, ASM, downregulation by specific siRNA leads to reduced FasL-induced lipid raft clustering and Fas aggregation on endothelial cell membrane
additional information
site-directed mutagenesis indicates that two histidine residues, His136 and His272, are essential for catalysis, overexpression of catalytically inactive nSMase1 has no effect on CD95-induced ceramide production
additional information
site-directed mutagenesis indicates that two histidine residues, His136 and His272, are essential for catalysis, overexpression of catalytically inactive nSMase1 has no effect on CD95-induced ceramide production
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
-
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
-
aSMase silencing by siRNA in human airway epithelial cells leads to increased caspase-3 cleavage
additional information
-
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
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
-
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
-
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
-
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
additional information
targeted knock-out mutations of LIPI-2 genes, including gene smcL, cause virulence defects, overview
additional information
-
targeted knock-out mutations of LIPI-2 genes, including gene smcL, cause virulence defects, overview
additional information
construction of SMase knockout mutants, the mutant strain is less virulent for mice than the wild-type strain using an infection model of the mouse mammary gland
additional information
-
construction of SMase knockout mutants, the mutant strain is less virulent for mice than the wild-type strain using an infection model of the mouse mammary gland
-
additional information
-
construction of nSMase2 and of nSMase1 knockout mice, the latter do not show lipid storage abnormalities nor deficient sphingomyelin metabolism, phenotype, overview
additional information
-
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
additional information
-
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
additional information
-
C-Terminal deletion mutants lose sphingomyelinase activity for hydrolysis of intact erythrocytes
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
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 10
stable from pH 5.0-10.0, the enzyme retains activity between pH 5 and 10 for 30 min
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
storage of very small volume cerebrospinal fluid aliquots, below 0.02 ml, at room temperature or above lead to the rapid loss of enzyme activity
4 - 60
the enzyme activity is stable between 4°C and 37°C for 30 min, activity drops abruptly above 37°C with less than 10% activity remaining at 50-60°C
50
55
56
65
55
-
plasma membrane and microsomes, 10 min, 15% activity, lysosomes, 10 min, 78% activity
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol, stabilization
reducing agents such as dithiothreitol stablize nSMase2 during preparation
the wild-type SMPD1 protein has a half-life of over 12 h. The half-life for the F572L protein is shorter, between 4 h and 8 h. The G247D mutation dramatically alters the stability of the mutant protein with a half-life of 2 h or less
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 25 mM citrate buffer, pH 5.9, 2 mg/ml cutsum, 50% glycerol, 5 mM EDTA, 1 mM dithiothreitol, more than 3 months
-
-20C, up to 1 year
10 mM Tris-HCl, pH 7.2, 0. 1% Triton X-100, 10 mM 2-mercaptoethanol, protein 0.1 mg/ml, more than 2 months
-
22°C, storage of very small volume cerebrospinal fluid aliquots, below 0.02 ml, at room temperature or above lead to the rapid loss of enzyme activity
-
4C, stable for several weeks
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
6130fold purification, using a Percoll gradient, pulled down with biotinylated sphingomyelin, and subjected to Mono Q anion exchange
-
ammonium sulfate precipitation, DEAE-cellulose column chromatography, butyl-Toyopearl column chromatography, DEAE-5PW HPLC column chromatography, Sephacryl S-300 gel filtration, Mono Q column chromatography, Heparin Hi-TRAP column chromatography, and Superose 12 gel filtration
-
ammonium sulfate precipitation, DEAE-Sepharose column chromatography, HiTrap Q column chromatography, Resource Q column chromatography, and Superdex 200 gel filtration
ammonium sulfate precipitation, HiTrap phenyl column chromatography, Q-Sepharose column chromatography, and Superdex 200 gel filtration
Ni-NTA resin column chromatography and Superdex 200 gel filtration
NP-40, CM-Sepharose, concanavalin A-Sepharose, Methyl-macroprep, isoelectric focusing
-
partial
recombinant enzyme-2-FLAG-6xHis construct from Escherichia coli by affinity chromatography
recombinant extracellular wild-type and L-selenomethionine-labeled enzyme from culture supernatant by anion exchange chromatography and gel filtration
-
recombinant haSMase, ammonium sulfate, Con A-Sepharose, Octyl-Sepharose, Matrex Gel Red A, DEAE-650
-
recombinant His-tagged enzyme from CHO cell culture medium by nickel affinity chromatography
recombinant nSMase
recombinant solubilized enzyme from Escherichia coli strain BL21(DE3) inclusion bodies by immunoaffinity chromatography
SE column chromatography, the enzyme is not retained in DEAE-Sepharose column equilibrated with 20 mM Tris-HCl buffer containing 0.075 M NaCl
-
Triton X-100, DE52, Butyl-Toyopearl, DEAE-5PW, Sephacryl S-300, Mono S, T-mSMase isoforms alpha, beta, gamma and delta, ammonium sulfate, Butyl-Toyopearl, Sephacryl S-300, Phenyl-5PW, DEAE-5PW, Resource S, S-mSMase isoforms epsilon and zeta
-
Triton X-100, DEAE-Sephacel, heparin-Sepharose, hydroxyapatite, Mono Q, Phenyl-Sepharose, Superose 12
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
alkaline sphingomyelinase, cloning and DNA and amino acid sequence determination and analysis from Hep-G2 cancer cells, transient expression of mutant alkaline sphingomyelinase forms in COS-7 cells
enzyme expressed from cDNA from HT-29 cells in COS-7 cells shows little alk-SMase activity, enzyme expressed from cDNA from Caco-2 cells in COS-7 cells is as active as wild-type enzyme
-
expressed in Sf9 insect cells
expression in Escherichia coli
expression in Escherichia coli and HEK293 kidney cells
expression of (E)GFP-fused wild-type nSMase2 and of several (E)GFP-fused truncated mutant nSMase2s possessing additional V5- or FLAG-tags in HEK-293 or MCF-7 cells
-
expression of nSMase2 in Saccharomyces cerevisiae and MCF7 breast cancer cells
expression of wild-type and mutant enzymes in Bacillus subtilis strain ISW1214
-
functional expression of a chimeric GFP-tagged SMase fused to a lysosomal sorting motif of lysosomal acid phosphatase in HEK-293 and CHO cells, sorting of the recombinant enzyme to lysosomes
-
functional overexpression in Rhodococcus erythropolis and secretion to the culture medium
gene plcHR2, expression and secretion of wild-type and L-selenomethionine-labeled enzyme
-
gene smcL, SmcL is encoded in the pathogeneicity island gene cluster LIPI-2, the chromosomal locus also encodes 10 internalin proteins, DNA and amino acid sequence determination and analysis, genetic organization, overview, phylogenetic analysis, subcloning in Escherichia coli
gene SMPD1, genotyping, expression of wild-type and mutant enzymes in COS-7 cells
gene SMPD1, quantitative real-time PCR expression analysis, recombinant His-tagged enzyme expression in CHO cells and secretion to the culture medium
gene SMPD1, splicing form ASM-5, genetic organisation of splicing variants, overview. Alternative splicing of the enzyme of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. Expression of FLAG-tagged ASM-5 in HeLa cells
gene SMPD1, splicing form ASM-6, genetic organisation of splicing variants, overview. Alternative splicing of the enzyme of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. Expression of FLAG-tagged ASM-6 in HeLa cells
gene SMPD1, splicing form ASM-7, genetic organisation of splicing variants, overview. Alternative splicing of the enzyme of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. Expression of FLAG-tagged ASM-7 in HeLa cells
gene SMPD1, transient overexpression of wild-type ASMase and mutant S508A in MCF-7 cells
-
gene SMPD3, expression of GFP-tagged and of N-terminally RFP-tagged enzyme in HEK-293-IL1R cells, recombinant expression of C-terminally FLAG-tagged enzyme and of enzyme-2-FLAG-6xHis construct in wildtype Escherichia coli strain Rosetta-gami2, and the mutated strain lacking endogenous thioredoxin, results in increased oligomer formation and lower enzyme activity, the phenotype can be rescued by with recombinant human thioredoxin
gene sph2, DNA and amino acid sequence determination and analysis, subcloning in Escherichia coli strains DH5alpha, recombinant expression in Escherichia coli strain BL21(DE3) in inclusion bodies
isozymes nSMase1 and nSMase2, overexpression of nSMase2 increases the shpingomyelin metabolism while overexpression of nSMase1 has no effect
-
nSMase overexpression as GST-tagged enzyme in Escherichia coli strain C43 (DE3)
-
nSMase2, DNA and amino acid sequence determination and analysis, overexpression of nSMase2 in DELTAISC1 yeast cells and in MCF-7 cells
overexpression in Saccharomyces cerevisiae strain JK9-3dDELTAIsc1p, lacking endogenous SMase activity
overexpression of nSMase1, the recombinant enzyme shows altered subcellular localization in the endoplasmic reticulum compared to the wild-type nSMase1 localized in the nucleus
-
overexpression of V5-tagged wild-type and mutant nSMases and of GFP-tagged mutant C3A/C5A in MCF-7 cells
-
quantitative expression analysis of acidic SMase in articular chondrocytes, overview
quantitative expression analysis of neutral SMase in articular chondrocytes, overview
splicing forms ASM-1 to ASM-4, genetic organisation of splicing variants, overview. Alternative splicing of the enzyme of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. Expression of FLAG-tagged ASM-1 in HeLa cells
transfection of murine and human glioma cell lines Gl-261 and U-373 with acid sphingomyelinase results in a marked sensitization of glioma cells to gemcitabine and doxorubicin, respectively
-
transient transfection of the His/V5-tagged wild-type and mutant recombinant ASM in CHO cells
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
3-acetyl-11-keto-beta-boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells at high concentration 3-acetyl-11-keto-beta-boswellic acid decreases both the mass of acid SMase protein and the mRNA levels of acid SMase in the cells
-
acid SMase protein is decreased by 20% in both Hep-G2 and Caco-2 cells at 0.1 mM ezetimibe
-
acid SMase protein is decreased by 25% in the intestine and by 34% in the liver at 0.1 mM ezetimibe
-
addition of tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma, and lipopolysaccharide to C2C12 cells elicits significant increases in enzyme activity levels
-
electrophilic compounds such as diethyl malate, methyl mercury, and cigarette smoke extracts significantly enhanced the expression of acidic sphingomyelinase 6fold in bladder carcinoma ECV-304 cells
-
ezetimibe up to 0.05 mM has no effects on acid phosphatase activity in both Hep-G2 and Caco-2 cells, no change of alkaline phosphatase activity is identified by ezetimibe
-
stimulation of bone marrow-derived mast cells with antigen results in about 2.5fold induction of enzyme activity
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain BL21(DE3) inclusion bodies is solubilized by 8 M urea
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
drug development
medicine
pharmacology
-
the enzyme is a potential target in the treatment of allergic reactions
diagnostics
-
the fecal sphingomyelinase activity reflects the human intestinal mucosa enzyme level and represents a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms
diagnostics
-
the extracellular enzyme from cerebrospinal fluid might hava a value as a potential biomarker for disease type, severity, progress or therapeutic success
drug development
-
TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis
drug development
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acid sphingomyelinase activity and sphingomyelin presence are necessary for efficient infection of cells by ebolavirus,the enzym eis a target for drug development
medicine
-
the sphingomyelin cycle is a potential therapeutic target for the prevention of wear debris induced osteolysis
medicine
-
inhibiting or stopping N-SMase activity is an important strategy to prevent neuron death from ischemia
medicine
-
Niemann-Pick A disease is a lysosomal storage disorder caused by a deficiency in acid sphingomyelinase activity, repeated intracerebroventricular infusions of recombinant human acid sphingomyelinase reduce the aberrant lysosomal accumulation of cholesterol and are effective at improving the disease phenotype in the acid sphingomyelinase-knockout mouse as indicated by a partial alleviation of the motor abnormalities
medicine
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ASM plays a complex and varied role in brain development, as well as in the pathogenesis of several common neurological diseases, ASM is particularly intriguing as an antioncogenic drug, ASM is associated with the type A Niemann-Pick disease, atherosclerosis, Wilson disease, hepatic autoimmune disease, alcohol-induced liver disease, cerebral ischemia, emphysema, cystic fibrosis, and cancer
medicine
-
systemic administration of recombinant acid sphingomyelinase (rhASM) into ASM deficient mice by intranasal instillation results in hydrolysis of the abnormal storage of sphingomyelin in lysosomes of the liver, spleen and lung, pulmonary administration of rhASM may represent an alternative route of delivery to address the visceral pathology associated with ASM deficiency
medicine
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recombinant human ASM has little or no effect on the growth of tumor cells at pH 7.4 even in combination with irradiation, however when the culture media is acidified to pH 6.5 to mimic the acidic microenvironment of solid tumors, ASM-mediated cell death is markedly enhanced when combined with irradiation
medicine
-
intrarectal instillation of recombinant human Alk-SMase once daily for 1 week significantly reduces the inflammation score and protects the colonic epithelium from inflammatory destruction in a rat colitis model
medicine
-
activation of acid sphingomyelinase is necessary and sufficient for microparticle release from glial cells and define key molecular effectors of microparticle formation and IL-1beta release, thus, opening new strategies for the treatment of neuroinflammatory diseases
medicine
-
acid sphingomyelinase activity and sphingomyelin presence are necessary for efficient infection of cells by ebolavirus, inhibition of the enzyme might be a threpeutic way
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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Release 2026.1 (March 2026)
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