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Information on EC 3.1.4.12 - sphingomyelin phosphodiesterase and Organism(s) Homo sapiens and UniProt Accession Q9NY59

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     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.
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: Q9NY59
Word Map
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The taxonomic range for the selected organisms is: Homo sapiens
Synonyms
A-SMase, acid SMase, acid smase1, acid smase2, acid smase3, acid smase4, acid sphingomyelinase, acid spingomyelinase, acid-SMase, acidic SMase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acid sphingomyelinase
acid spingomyelinase
247
-
acidic SMase
247
-
acidic sphingomyelinase
247
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alk-SMase
alkaline SMase
247
-
alkaline sphingomyelinase
aSMase
Beta-hemolysin
-
-
-
-
Beta-toxin
-
-
-
-
hnSMase
247
-
hSMase
247
-
intestinal alkaline sphingomyelinase
247
-
Lyso-PAF-PLC
-
-
-
-
magnesium-dependent neutral sphingomyelinase
247
-
N-SMase
N-SMase2
247
-
neutral SMase
247
-
neutral sphingomyelinase
neutral sphingomyelinase 2
neutral sphingomyelinase-1
247
-
neutral sphingomyelinase-2
247
-
neutral sphingomyelinase-3
247
-
neutral sphingomyelinases
247
-
neutral sphingomylinase 2
274839
-
NPP7
274838
-
nSMase
nSMase-1
247
-
nSMase1
nSMase2
nSMase3
247
-
phosphodiesterase, sphingomyelin
-
-
-
-
rhASM
247
-
S-SMase
247
-
secretory sphingomyelinase
247
-
SKNY
247
-
SMase
smdp3
274839
-
SMPD-1
247
-
SMPD1
247
-
smpd2
274835
-
Smpd3
247
-
SMPD4
247
-
SMPLC
-
-
-
-
sphingomyelin phosphodiesterase
-
-
-
-
sphingomyelin phosphodiesterase 1
sphingomyelin phosphodiesterase-1
247
-
sphingomyelinase
sphingomyelinase C
-
-
-
-
additional information
247
alk-SMase is a member of the NPP, i.e. nucleotide diphosphatase/phosphodiesterase, family
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a sphingomyelin + H2O = a ceramide + phosphocholine
show the reaction diagram
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases
a sphingomyelin + H2O = a ceramide + phosphocholine
show the reaction diagram
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
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
sphingomyelin cholinephosphohydrolase
Has very little activity on phosphatidylcholine.
CAS REGISTRY NUMBER
COMMENTARY hide
9031-54-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
2-(N-hexadecanoylamino)-4-nitrophenylphosphorylcholine + H2O
2-(N-hexadecanoylamino)-4-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphocholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
show the reaction diagram
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
bis(4-methylumbelliferyl)-phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
show the reaction diagram
choline-methyl-sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
-
?
lissamine-rhodamine dodecanoyl sphingosyl phosphocholine + H2O
?
show the reaction diagram
-
neutral sphingomyelinase
-
-
?
lyso-platelet-activating factor + H2O
1-alkylglycerol + choline phosphate
show the reaction diagram
-
103fold higher activity than with sphingomyelin in the absence of detergent
-
?
lyso-platelet-activating factor + H2O
alkylglycerol + choline phosphate
show the reaction diagram
-
55% of activity with sphingomyelin in the absence of detergent
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
show the reaction diagram
N-methylsphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
show the reaction diagram
phosphatidylethanolamine + H2O
diacylglycerol + phosphorylethanolamine
show the reaction diagram
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
show the reaction diagram
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
show the reaction diagram
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
show the reaction diagram
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
sphingomyelin + H2O
N-acylsphingosine + choline phosphate + ?
show the reaction diagram
-
-
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
show the reaction diagram
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
show the reaction diagram
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
can replace Mn2+
Cu2+
-
6fold increase in activity at 0.1 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
EDTA
5 mM, complete inhibition, activity is comletely restored by the subsequent addition of 10 mM Mg2+ or Mn2+
GW4869
specific inhibition
(1-aminodecane-1,1-diyl)bis(phosphonic acid)
-
a substrate analogue inhibitor of aSMase
1,10-phenanthroline
-
-
2'-AMP
-
mixture with 3'-AMP
27-Hydroxycholesterol
-
inhibition of acid sphingomyelinase; inhibition of neutral sphingomyelinase occurs at a posttranscriptional level
3',5'-cAMP
-
IC50: above 0.5 mM
3'-AMP
-
mixture with 2'-AMP
3-acetyl-11-keto-beta-boswellic acid
-
62% inhibition of acid SMase at 0.1 mM
3-O-methylsphingomyelin
-
-
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
3-[benzyl(tert-butyl)amino]-1-(4-nitrophenyl)propan-1-one
-
-
5'-AMP
-
-
5-adenoylimino phosphate
-
IC50: above 0.5 mM
AD2765
-
a substrate analogue inhibitor of aSMase
adenine-9-beta-D-arabinofuranoside 5'-monophosphate
-
-
adeno 5'-diphosphate
-
IC50: above 0.5 mM
adeno-2',3'-cyclic phospho 5'-monophosphate
-
IC50: 0.2 mM
adeno-2',3'-cyclic phospho 5'-phosphosulfate
-
IC50: 0.5 mM
adenosine 3',5'-diphosphate
-
-
adenosine 5'-monophosphate
-
periodate-oxidized and an isomer with arabinose instead of ribose as sugar component
Adenosine 5'-O-thiomonosulfate
-
-
adenosine 5'-phosphosulfate
-
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ADP
-
IC50: 0.3 mM
alpha-mangostin
-
a xanthone from the bark of Garcinia speciosa
amitriptyline
amlodipine
-
-
AMP
-
IC50: 0.08 mM, non-competitive inhibition
astemizole
-
-
ATP
-
IC50: 0.8 mM
benztropine
-
-
bepridil
-
-
Brij 56
-
-
C11AG
-
inhibits N-SMases in T-cells and macrophages
Ca2+
-
slight
camylofin
-
-
Cetylpyridinium chloride
-
-
CHAPS
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
chlorprothixene
-
-
cholate
-
-
clomiphene
-
-
cloperastine
-
-
cowanin
-
a xanthone from the bark of Garcinia speciosa
cowanol
-
a xanthone from the bark of Garcinia speciosa
curcumin
-
inhibits acid SMase, but not neutral and alkaline SMase, in Caco-2 cells with an antiproliferative effect, the effect is more potent in monolayers than in polarised cells, metabolis effects, overview
cyclobenzaprine
-
-
cyproheptadine
-
-
D609
-
nonspecific sphingomyelinase inhibitor
desipramine
dichloroisocoumarin
-
-
dithioerythritol
-
-
dithiothreitol
-
-
doxepine
-
-
drofenine
-
-
EDTA
-
alk-SMase activity with platelet-inactivating factor
Fe3+
-
-
fendiline
-
-
fluoxetine
-
-
glutathione
-
-
GW4869
imipramine
lysophosphatidic acid
-
IC50: 0.04 mM
mannose 6-phosphate
-
Niemann-Pick disease fibroblasts
manumycin A
-
-
maprotiline
-
-
Mn2+
-
above 0.5 mM
N-tosyl-L-phenylalanyl chloromethyl ketone
-
-
NAD+
-
IC50: above 0.5 mM
NADP+
-
IC50: above 0.5 mM
norfluoxetine
-
-
nortriptyline
-
-
oxidized glutathione
reversible inhibition of nSMase1
paroxetine
-
-
peroxynitrite
irreversible inhibition of nSMase1
phosphate
phosphatidyl inositol-3,5-bisphosphate
-
-
phosphatidyl-myo-inositol 3,4,5-triphosphate
-
IC50: 0.003 mM
phosphatidyl-myo-inositol 4,5-diphosphate
-
IC50: 0.25 mM
phosphatidylcholine
-
IC50: 2 mM
phosphatidylinositol
-
-
phosphatidylinositol 4',5'-bisphosphate
-
-
phosphatidylinositol-4,5-bisphosphate
-
-
phosphorylcholine
-
-
pimethixene
-
-
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
promazine
-
-
Promethazine
-
-
pronase E
-
reduction of stimulation of the two activator proteins
-
protriptyline
-
-
reactive oxygen species
reversible inhibition of nSMase1
-
scyphostatin
sertraline
-
-
sphingomyelin
-
strong competitive inhibition of platelet-inactivating factor hydrolysis
sphingosylphosphocholine
-
-
SR33557
-
the calcium channel inhibitor performs indirect inhibition of aSMase
suloctidil
-
-
sulphydryl reagents
-
-
terfenadine
-
-
triflupromazine
-
-
Triton X-100
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dioleoyl-phosphatidylserine
0.05 mM, 4fold activation
phosphatidylethanol
0.05 mM, 2fold activation
phosphatidylglycerol
activates nSMase2
phosphatidylserine
Activator proteins
-
from human spleen, two forms of
-
albumin
-
20% activation of enzyme A and B
-
arachidonic acid
-
approx. 3fold activation at 0.5 mM
bile salt
-
dependent on, particularly taurocholate and taurochenodeoxycholate
ceramide
-
-
cholate
-
-
Cutsum
-
-
-
daunorubicin
-
-
deoxycholate
-
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Detergents
-
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Diacylglycerols
-
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galectin-I
-
human, induces apoptosis and initiates the acid SMase-mediated release of ceramide
-
glycocholate
-
-
H2O2
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, overview
Lipids
-
saturated and unsaturated fatty acids
-
monoacylglycerols
-
-
ONOO-
-
peroxynitrite specifically activates the acidic sphingomyelinase
phorbol 12-myristate 13-acetate/protein kinase Cdelta
-
activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation, which is mediated by phorbol 12-myristate 13-acetate, that induces also membrane translocation of ASMase, formation of a novel PKCdelta-ASMase complex after PMA stimulation, mechanism, overview
-
phosphatidic acid
-
-
phosphatidylinositol
-
-
phosphatidylserine
protein kinase C-zeta
-
mediates the activation of N-SMase by 1,25-dihydroxyvitamin D3, while protein kinase C-delta inhibits the activation
-
Salts
-
trihydroxy- and dihydroxy-bile salt
-
saposin C
-
presence of sphingolipid activator proteins, e. g. saponsins, is not essential for activity. Saposin C increases activity of the P153A mutant enzyme, but does not result in complete restoration of the activity
-
staurosporine
-
activates neutral spingomyelinase in a multiphasic manner
taurochenodeoxycholate
-
-
taurocholate
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
-
TNFalpha
-
S-SMase cytokine TNFalpha activation, completely abrogated by desipramine, overview
-
triacylglycerols
-
-
Tripalmitoylglycerol
-
-
Triton X-100
tumor necrosis factor
-
induces N-SMase activity
-
tumor necrosis factor-alpha
-
activates neutral spingomyelinase in a multiphasic manner
-
Tween 20
-
-
additional information
-