Information on EC 3.1.4.12 - sphingomyelin phosphodiesterase

New: Word Map on EC 3.1.4.12
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
3.1.4.12
-
RECOMMENDED NAME
GeneOntology No.
sphingomyelin phosphodiesterase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a sphingomyelin + H2O = a ceramide + phosphocholine
show the reaction diagram
-
-
-
-
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
O60906, Q9NY59
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, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview
P09599
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
O60906, Q9NY59
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, overview
-
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, structure-function analysis, overview
Q9RLV9
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, structure-function analysis, overview
Listeria ivanovii nSMase
-
-
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, overview
Helicobacter pylori nSMase
-
-
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, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview
Bacillus cereus nSMase
-
-
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
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
sphingolipid biosynthesis (mammals)
-
-
Sphingolipid metabolism
-
-
sphingomyelin metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
sphingomyelin cholinephosphohydrolase
Has very little activity on phosphatidylcholine.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A-SMase
-
-
acid SMase
-
-
acid SMase
-
-
acid smase1
D3TNH1
-
acid smase2
I2CMF9
-
acid smase3
I2CMG0
-
acid smase4
I2CMG1
-
acid sphingomyelinase
-
-
-
-
acid sphingomyelinase
-
-
acid sphingomyelinase
E9LUE7, E9LUE8, E9LUE9, P17405
-
acid sphingomyelinase
Q8IUN0
-
acid sphingomyelinase
Mus musculus C57BL/6J
-
-
-
acid sphingomyelinase
Rattus norvegicus Sprague-Dawley
-
-
-
acid sphingomyelinase
-
-
acid spingomyelinase
-
-
acid-SMase
-
-
acidic SMase
Q9BDR3
-
acidic SMase
-
-
acidic sphingomyelinase
-
-
acidic sphingomyelinase
-
-
alk-SMase
-
key enzyme in the intestinal tract for digestion of dietary sphingomyelin
alk-SMase
Q6UWV6
-
alkaline SMase
-
-
alkaline sphingomyelinase
-
-
-
-
alkaline sphingomyelinase
-
-
alkaline sphingomyelinase
Q6UWV6
-
alkaline sphingomyelinase
-
-
alkaline sphingomyelinase
-
key enzyme responsible for sphingomyelin digestion in the gut
alkaline sphingomyelinase
-
-
alpha-toxin
Clostridium perfringens 8-6
-
-
-
ASM
-
-
ASM
E9LUE7, E9LUE8, E9LUE9, P17405
-
ASM
Mus musculus C57BL/6J
-
-
-
ASM
Rattus norvegicus Sprague-Dawley
-
-
-
aSMase
-
-
-
-
aSMase
-
-
aSMase
Q8IUN0
-
aSMase1
D3TNH1, I2CMF9, I2CMG0, I2CMG1
gene name
Bc-SMase
Bacillus cereus IAM1029
-
;
-
Beta-hemolysin
-
-
-
-
Beta-toxin
-
-
-
-
bSMase
-
-
ceramide-phosphocholine phosphodiesterase
-
-
ceramide-phosphocholine phosphodiesterase
Rattus norvegicus Fischer 344
-
-
-
hnSMase
-
-
hSMase
-
-
intestinal alkaline sphingomyelinase
-
-
intestinal sphingomyelinase
-
-
Lyso-PAF-PLC
-
-
-
-
MA-nSMase
D6MZJ6
-
magnesium-dependent neutral sphingomyelinase
-
-
membrane associated neutral sphingomyelinase
-
-
Mg++-dependent sphingomyelinase
P59116
-
Mg++-dependent sphingomyelinase
Leptospira interrogans 56601
P59116
-
-
mitochondrial-associated neutral sphingomyelinase
D6MZJ6
-
N-mSMase
-
-
N-Sase
Rattus norvegicus Fischer 344
-
-
-
N-SMase
-
-
-
-
N-SMase
P09599
-
N-SMase
Bacillus cereus nSMase
P09599
-
-
N-SMase
Helicobacter pylori nSMase
-
-
-
N-SMase
O60906, Q9NY59
-
N-SMase
Q9RLV9
-
N-SMase
Listeria ivanovii nSMase
Q9RLV9
-
-
N-SMase
-
-
N-SMase2
-
-
neutral SMase
-
-
neutral SMase
-
-
neutral SMase
-
-
neutral SMase
-
-
neutral SMase
-
-
neutral SMase 1
Q4LEU0
-
neutral sphingomyelin-specific phospholipase C
-
-
neutral sphingomyelin-specific phospholipase C
Rattus norvegicus Fischer 344
-
-
-
neutral sphingomyelinase
-
-
-
-
neutral sphingomyelinase
P09599
-
neutral sphingomyelinase
Bacillus cereus IAM1029
-
-
-
neutral sphingomyelinase
Bacillus cereus nSMase
P09599
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
Helicobacter pylori nSMase
-
-
-
neutral sphingomyelinase
O60906
-
neutral sphingomyelinase
Q9NY59
-
neutral sphingomyelinase
Q9RLV9
-
neutral sphingomyelinase
Listeria ivanovii nSMase
Q9RLV9
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
Plasmodium falciparum Honduras 1
-
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase
-
-
neutral sphingomyelinase 1
Q4LEU0
neutral SMase 1 acts as a mediator of stress-induced apoptosis
neutral sphingomyelinase 1
Q9ET64
-
neutral sphingomyelinase 2
-
-
neutral sphingomyelinase 2
-
-
neutral sphingomyelinase 2
Q9NY59
-
neutral sphingomyelinase 2
-
-
neutral sphingomyelinase 2
Q9JJY3
-
neutral sphingomyelinase C
-
-
neutral sphingomyelinase-1
-
-
neutral sphingomyelinase-2
-
-
neutral sphingomyelinase-2
Q9JJY3
-
neutral sphingomyelinase-2
-
-
neutral sphingomyelinase-3
-
-
neutral sphingomyelinase-C
-
-
neutral sphingomyelinase-C
Entamoeba histolytica HM1
-
-
-
neutral sphingomyelinases
-
-
neutral sphingomylinase 2
Q9NY59
-
NPP7
Q6UWV6
-
nSM1
-
isoform
nSM3
-
isoform
nSMase
-
-
-
-
nSMase
Bacillus cereus IAM1029
-
-
-
nSMase
-
-
nSMase
Q9JJY3
-
nSMase 1
Q9ET64
-
nSMase-1
-
-
NSMase-2
Q9JJY3
-
nSMase1
-
-
nSMase1
O60906
-
nSMase2
-
-
nSMase2
Q9NY59
-
phosphodiesterase, sphingomyelin
-
-
-
-
phospholipase C/sphingomyelinase
-
-
PlcHR2
-
; a phospholipase C/sphingomyelinase, the sphingomyelinase, but not the phospholipase C activity, is essential for hot-cold hemolysis
PlcHR2 toxin
-
-
rhASM
-
-
S-mSMase
-
ammonium sulfate extracted isoforms epsilon and zeta
S-SMase
-
-
S-SMase
I4DXK5
-
S-SMase
I4DXK5
-
-
secretory sphingomyelinase
-
-
SKNY
-
-
SMase
-
-
-
-
SMase
-
-
SMase
Clostridium perfringens 8-6
-
-
-
SMase
D3TNH1, I2CMF9, I2CMG0, I2CMG1
-
SMase
Plasmodium falciparum Honduras 1
-
-
-
SMase
I4DXK5
-
SMase
I4DXK5
-
-
SMase C
-
-
SMase I
-
-
SMase-C
Entamoeba histolytica HM1
-
-
-
SMC
Streptomyces griseocarneus NBRC13471
A6P7M9
-
-
SmcL
Q9RLV9
-
smdp3
Q9NY59
-
SMPD
D6MZJ6
-
SMPD-1
-
-
SMPD1
-
-
smpd2
O60906
-
Smpd3
-
-
Smpd3
Q9JJY3
-
SMPD4
-
-
SMPLC
-
-
-
-
Sph2
Leptospira interrogans 56601
P59116
-
-
sphingomyelin phosphodiesterase
-
-
-
-
sphingomyelin phosphodiesterase 1
-
-
sphingomyelin phosphodiesterase 1
P17405
-
sphingomyelin phosphodiesterase 3
Q9JJY3
-
sphingomyelin phosphodiesterase 5
D6MZJ6
-
sphingomyelin phosphodiesterase-1
-
-
sphingomyelinase
-
-
-
-
sphingomyelinase
Bacillus cereus IAM1029
-
;
-
sphingomyelinase
-
-
sphingomyelinase
Q9BDR3
-
sphingomyelinase
-
-
sphingomyelinase
Clostridium perfringens 8-6
-
-
-
sphingomyelinase
D3TNH1, I2CMF9, I2CMG0, I2CMG1
-
sphingomyelinase
-
-
sphingomyelinase
Q9RLV9
-
sphingomyelinase
-
-
sphingomyelinase
-
-
sphingomyelinase C
-
-
-
-
sphingomyelinase C
-
-
sphingomyelinase C
A6P7M9
-
sphingomyelinase C
Streptomyces griseocarneus NBRC13471
A6P7M9
-
-
sphingomyelinase C
I4DXK5
-
sphingomyelinase C
I4DXK5
-
-
sphingomyelinase/hemolysin
-
-
Sphmase
-
-
T-mSMase
-
Triton X-100 isoforms alpha, beta, gamma and delta
mnSMase
-
-
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
CAS REGISTRY NUMBER
COMMENTARY
9031-54-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
nSMase
SwissProt
Manually annotated by BRENDA team
Bacillus cereus IAM1029
-
-
-
Manually annotated by BRENDA team
Bacillus cereus nSMase
nSMase
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
bull
-
-
Manually annotated by BRENDA team
multiple N-SMase isozymes, one of which is nSMase2
-
-
Manually annotated by BRENDA team
Clostridium perfringens 8-6
-
-
-
Manually annotated by BRENDA team
strain HM-1:IMSS
-
-
Manually annotated by BRENDA team
aSMase1; gene asmase1
UniProt
Manually annotated by BRENDA team
aSMase2; gene asmase2
UniProt
Manually annotated by BRENDA team
aSMase3; gene asmase3
UniProt
Manually annotated by BRENDA team
aSMase4; gene asmase4
UniProt
Manually annotated by BRENDA team
Helicobacter pylori nSMase
nSMase
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
; nSMase2 expression is up-regulated during cell growth
-
-
Manually annotated by BRENDA team
acid sphingomyelinase, gene SMPD-1
-
-
Manually annotated by BRENDA team
acid sphingomyelinase, splicing form ASM-5; gene SMPD1
UniProt
Manually annotated by BRENDA team
acid sphingomyelinase, splicing form ASM-6; gene SMPD1
UniProt
Manually annotated by BRENDA team
acid sphingomyelinase, splicing form ASM-7; gene SMPD1
UniProt
Manually annotated by BRENDA team
acid sphingomyelinase, splicing forms ASM-1 to ASM-4; gene SMPD1
UniProt
Manually annotated by BRENDA team
controls and patients with different variants of Gaucher disease
-
-
Manually annotated by BRENDA team
gene ENPP7; gene ENPP7
SwissProt
Manually annotated by BRENDA team
gene SMPD1
-
-
Manually annotated by BRENDA team
gene SMPD1
UniProt
Manually annotated by BRENDA team
gene SMPD1
UniProt
Manually annotated by BRENDA team
haSMase deficiency due to mutations in haSMase gene leads to Niemann-Pick disease, an autosomal recessive sphingolipidosis
-
-
Manually annotated by BRENDA team
healthy individuals and patient with chronic heart failure
-
-
Manually annotated by BRENDA team
isozymes nSMase2 and nSMase1
-
-
Manually annotated by BRENDA team
Niemann-Pick disease patients
-
-
Manually annotated by BRENDA team
nSMase1 or smpd2; nSMase1 or smpd2
SwissProt
Manually annotated by BRENDA team
nSMase2; nSMase2
SwissProt
Manually annotated by BRENDA team
one form of Niemann-Pick disease is caused by a deficiency of acid sphingomyelinase
-
-
Manually annotated by BRENDA team
patients with atopic dermatitis
-
-
Manually annotated by BRENDA team
serovar Lai, gene sph2 or LA_1029 encoding isozyme Sph2
UniProt
Manually annotated by BRENDA team
Leptospira interrogans 56601
serovar Lai, gene sph2 or LA_1029 encoding isozyme Sph2
UniProt
Manually annotated by BRENDA team
SmcL; a specific ruminant pathogen, gene smcL
EMBL
Manually annotated by BRENDA team
Listeria ivanovii nSMase
nSMase
EMBL
Manually annotated by BRENDA team
recombinant
-
-
Manually annotated by BRENDA team
gene SMPD1
-
-
Manually annotated by BRENDA team
gene SMPD3
SwissProt
Manually annotated by BRENDA team
heterozygous sv129 x BL/6 background mice
-
-
Manually annotated by BRENDA team
isozymes nSMase1 and nSMase2
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
strain Honduras 1, no. 1-CDC
-
-
Manually annotated by BRENDA team
Plasmodium falciparum Honduras 1
strain Honduras 1, no. 1-CDC
-
-
Manually annotated by BRENDA team
; strain PAO1
-
-
Manually annotated by BRENDA team
strain PA01 derivative ADD1976, plcHR2
-
-
Manually annotated by BRENDA team
strain TK4
-
-
Manually annotated by BRENDA team
healthy and permanently bile diverted male Wistar rats
-
-
Manually annotated by BRENDA team
male Fisher 344 rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
strain Fischer 344
-
-
Manually annotated by BRENDA team
young rats of 3-4 months and aged rats of 20-22 months
-
-
Manually annotated by BRENDA team
Rattus norvegicus Fischer 344
strain Fischer 344
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
strain NBRC13471
UniProt
Manually annotated by BRENDA team
Streptomyces griseocarneus NBRC13471
strain NBRC13471
UniProt
Manually annotated by BRENDA team
boar
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
P59116
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
I4DXK5
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
Q8IUN0
the enzyme is a member of the metallophosphoesterase enzyme family
evolution
Leptospira interrogans 56601
-
the enzyme belongs to the DNase I superfamily, which contains the exo-endo-phosphatase domain, the domain lacks only in isozyme Sph4, all isozymes lack the beta-hairpin loop, the organism encodes genes Sph1, Sph2, Sph3, Sph4 and SphH, structure comparisons, overview
-
evolution
-
the enzyme from Streptomyces seems to be a typical bacterial SMase with a primary structure unusual for known bacterial SMases, primary structure comparisons and phylogenetic analysis
-
malfunction
-
acid SMase-deficient mice show reduced pulmonary ceramide levels and attenuated leukocyte influx into the alveolar space
malfunction
-
an inborn deficiency in aSMase activity leads to a lysosomal storage of sphingomyelin and a fatal pathology that has been designated as the type A and type B of Niemann-Pick-disease
malfunction
-
deficiency of the enzyme leads to lysosomal accumulation of sphingomyelin resulting in in Niemann-Pick types A and B diseases
malfunction
-
glucose intolerance in ASM-/- mice
malfunction
-
loss of nSMase activity leads to a Big-Eye-like phenotype, and affect s protein trafficking, as well as VSG trafficking, overview
malfunction
-
treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
malfunction
-
acid sphingomelin-specific drugs and multiple small interfering RNAs strongly inhibit the infection by ebolavirus and ebolavirus glycoprotein pseudotyped viruses but not by the pseudotypes bearing the glycoprotein of vesicular stomatitis virus, overview. ASMase siRNA-treated cells resist EBOV infection
malfunction
-
decreasing ceramide levels by inhibiting ceramide synthase or neutral sphingomyelinase 2 leads to translocation of membrane-bound aPKC to the cytosol, concurrent with its activation and the phosphorylation of its substrate Aurora kinase A. Ceramide depletion leads to translocation of aPKC from the primary cilium and the apicolateral cell membrane to the cytosol
malfunction
-
mediates a variety of stress-related cellular processes. The pathological effects of dysregulated acid sphingomyelinase activity are evident in several human diseases and indicate an important functional role for acid sphingomyelinase regulation. Alternative splicing of acid sphingomyelinase is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular enzyme activity
malfunction
P17405
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
Rattus norvegicus Sprague-Dawley
-
treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
-
malfunction
Mus musculus C57BL/6J
-
glucose intolerance in ASM-/- mice
-
metabolism
-
all-trans-retinoic acid induction of nSMase2 stimulates an increase in ceramide levels followed by G0/G1 growth arrestin MCF-7 cells. nSMase2 siRNA significantly inhibits all-trans-retinoic acid effects on ceramide levels and growth arrest. Neither all-trans-retinoic acid stimulation nor nSMase2 overexpression have significant effects on classical cell cycle regulators such as p21/WAF1 or retinoblastoma. In contrast, all-trans-retinoic acid suppresses phosphorylation of ribosomal S6 kinase and its downstream targets S6 and eIF4B, which is significantly inhibited by nSMase2 siRNA. nSMase2 overexpression is sufficient to suppress S6K phosphorylation and signaling
metabolism
-
ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. Loss of sphingosine kinase-1 diminishes ASM-mediated AKT phosphorylation, but exogenous S1P induces AKT activation in hepatocytes. In contrast, SphK1 deficiency does not affect AMPK activation. The SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation
metabolism
-
interaction in the NO/NOS and SMases/ceramide signaling pathways, overview
metabolism
-
the essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei
metabolism
-
key enzyme in sphingolipid metabolism
physiological function
-
in HepG2 cells SMase treatment significantly enhances the esterification of cholesterol by a 50% with respect to control cells
physiological function
-
acid sphingomyelinase catalyzes the cleavage of sphingomyelin to generate ceramide. Ceramide levels may be a determining factor in osteoclast formation. As ceramide levels are also regulated by sphingosine kinase, as well as ASM. ASM differentially regulates sphingosine kinase 1 and sphingosine kinase 2 expression, the sphingosine kinases show opposing effects on osteoclast formation
physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
physiological function
-
all-trans-retinoic acid regulation of nSMase2, overview
physiological function
-
alpha-toxin, a major determinant of Clostridium perfringens toxicity, exhibits both phospholipase C and sphingomyelinase activities with distinct, but partially overlapping and interacting active sites
physiological function
-
APLs, the enzymatic activity of nSMase2 is dependent on anionic phospholipids, structural requirements for APL-selective binding of nSMase2, overview. nSMase2 interacts specifically and directly with several APLs, including phosphatidylserine and phosphatidic acid. Identification of two discrete APL binding domains in the N terminus of nSMase2, the nSMase2 N-terminal domain is essential for nSMase interaction with APLs. APL binding domains are important for nSMase2 to localize at the plasma membrane
physiological function
-
aSMase is known to induce apoptosis in a variety of cell lines and is emerging as an important mediator of inflammation in various pathological backgrounds
physiological function
-
role for A-SMase in the release of plasma membrane-derived microparticles, overview A-SMase is a cation-independent hydrolase contributing to the catabolism of sphingomyelin in lysosomes. Stress is believed to activate A-SMase to generate ceramide, which serves as a cellular mediator in initiating apoptotic response, the process is controlled by NO, detailed overview. A-SMase activity is also crucial for developmental programmed cell death of oocytes. Modeling of A-SMase function in apoptosis, overview
physiological function
-
the enzyme controls hydrolysis of surface membrane sphingomyelin molecules, thus allowing nutrients, but not host antibodies, to access proteins at the host-parasite interface
physiological function
-
the neutral sphingomyelinase is essential for growth and survival of the parasite. The formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface
physiological function
-
as a key enzyme in sphingolipid metabolism, acid sphingomyelinase is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. Increased activity of the lysosomal form is associated with various pathological conditions
physiological function
-
as a key enzyme in sphingolipid metabolism, acid sphingomyelinase is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. Increased activity of the lysosomal form is associated with various pathological conditions, the extracellular enzyme from cerebrospinal fluid migh also play a role in human disease
physiological function
-
critical role(s) of sphingomyelinase and ceramidase during pregnancy and lactation and their downstream effects on adult progeny fitness. The mother provides her offspring with nutrients required for development solely via intrauterine lactation
physiological function
D3TNH1, I2CMF9, I2CMG0, I2CMG1
critical role(s) of sphingomyelinase and ceramidase during pregnancy and lactation and their downstream effects on adult progeny fitness. The mother provides her offspring with nutrients required for development solely via intrauterine lactation. aSMase1 is regulated and expressed in a pregnancy and milk gland-specific manner
physiological function
-
neural differentiation of human embryonic stem cells to neuroprogenitors is concurrent with a threefold elevation of ceramide, in particular, saturated, long-chain C16:0 ceramide (N-palmitoyl sphingosine) and nonsaturated, very long chain C24:1 ceramide (N-nervonoyl sphingosine), involving the enzyme activity, critical role of ceramide generated by nSMase2 in stem cell ciliogenesis and differentiation
physiological function
Q9JJY3
neutral sphingomyelinase-2 is the major sphingomyelinase activated in response to proinflammatory cytokines and during oxidative stress. The enzyme may be a novel substrate for thioredoxin
physiological function
-
rhinovirus and measles virus each require the enzyme activity during early stages of infection, as well as the ebolavirus. Both sphingomyelin and ceramide are important components of lipid rafts and are potent signaling molecules. Each plays roles in mediating macropinocytosis, which has been shown to be important for ebolavirus infection. The binding of virus-like particles to cells is strongly associated with surface-localized ASMase as well as sphingomyelin-enriched sites, overview
physiological function
-
role for the enzyme in the acceleration of the production of TNF-induced interleukin-6 as a pro-inflammatory cytokine, electrophiles can potentiate inflammation response by up-regulating of ASMase expression following formation of lipid rafts. Expression of ASMase facilitates the clustering of TNFR1 in the lipid raft that in turn enhanced the sensibility of TNF-alpha for the production of interleukin-6
physiological function
-
the dimeric enzyme is an important virulence factor in model Pseudomonas aeruginosa infections and is selectively cytotoxic, at picomolar concentrations to mammalian endothelial cells
physiological function
-
the enzyme is a regulator of mast cell function, detailed overview. Degranulation of mast cells is stimulated by store-operated Ca2+-entry, while in other cell types, Ca2+-entry is modified by ceramide. Exogenously added ceramide has been shown to trigger mast cell apoptosis. Ceramide is produced from sphingomyelin by acid sphingomyelinase. Decrease in body temperature upon the induction of systemic anaphylaxis is significantly less pronounced in asm-/- mice than in asm+/+ mice
physiological function
-
the enzyme is a virulence factor for septicemia. Ganglioside GM3 is the primary cellular receptor for the enzyme, and the beta-hairpin region is the tethering region for gangliosides
physiological function
P59116
the recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
physiological function
Rattus norvegicus Sprague-Dawley
-
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
Leptospira interrogans 56601
-
the recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
-
physiological function
Bacillus cereus IAM1029
-
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
Mus musculus C57BL/6J
-
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
Clostridium perfringens 8-6
-
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
-
metabolism
Rattus norvegicus Sprague-Dawley, Mus musculus C57BL/6J
-
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
-
additional information
-
aSMase exists in two forms: a Zn2+-independent lysosomal aSMase, L-SMase, and a Zn2+-dependent secreted aSMase, S-SMase, that arise from alternative trafficking of a single protein precursor. Mechanism of aSMase maturation involving C-terminal proteolytic processing within, or in close proximity to, endolysosomes, overview
additional information
-
besides the aSMase, an alkaline sphingomyelinase and two neutral sphingomyelinases 1 and 2, nSMase1 and nSMase2, exist
additional information
-
comparison of in vivo activity of nSMase in Schistosoma mansoni with the activity in Schistosoma haematobium, overview
additional information
-
establishing enzyme activity in lipid vesicles, method development, overview. Both lipase activities are sensitive to vesicle size, but in opposite ways: while phospholipase C is higher with larger vesicles, sphingomyelinase activity is lower
additional information
-
from the gene of A-SMase, another product may be generated, i.e., the secretory SMase, which is very similar to A-SMase, differing only in the intracellular trafficking and in the need of zinc for activation
additional information
Q9JJY3
a redox sensitive enzyme
additional information
Q8IUN0
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
P59116
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
Leptospira interrogans 56601
-
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
Clostridium perfringens 8-6
-
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
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
show the reaction diagram
Streptomyces griseocarneus, Streptomyces griseocarneus NBRC13471
A6P7M9
2.11% activity compared to sphingomyelin
-
-
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
show the reaction diagram
Streptomyces griseocarneus, Streptomyces griseocarneus NBRC13471
A6P7M9
9.04% activity compared to sphingomyelin
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
show the reaction diagram
Streptomyces griseocarneus, Streptomyces griseocarneus NBRC13471
A6P7M9
4.93% activity compared to sphingomyelin
-
-
?
1,2-dioleoyl-sn-glycero-3-phosphocholine + H2O
?
show the reaction diagram
A6P7M9
0.7% activity compared to sphingomyelin
-
-
?
1-alkyl-lyso-platelet activating factor + H2O
1-alkylglycerol + choline phosphate
show the reaction diagram
-
-
-
?
1-O-octadecyl-2-lyso-platelet-activating factor + H2O
1-O-octadecyl-sn-glycerol + phosphocholine
show the reaction diagram
Q4LEU0
very little activity
-
-
?
2-(N-hexadecanoylamino)-4-nitrophenylphosphorylcholine + H2O
2-(N-hexadecanoylamino)-4-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-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
-
-
-
-
?
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
-
-
-
-
?
4-nitrobenz-2-oxa-1,3-diazole-sphingosylphosphorylcholine + H2O
4-nitrobenz-2-oxa-1,3-diazole-sphingosine + choline phosphate
show the reaction diagram
-
-
-
?
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
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 + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
Clostridium perfringens, Clostridium perfringens 8-6
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
Q9JJY3
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
I4DXK5
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
P59116
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
E9LUE7, E9LUE8, E9LUE9, P17405
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
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
show the reaction diagram
Q8IUN0
-
i.e. an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
6-N-(7-nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
Q9JJY3
6-N-(7-Nnitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
E9LUE7, E9LUE8, E9LUE9, P17405
using radiolabelled C12-sphingomyelin as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
using the fluorescent substrate BODIPY-FL-C12-SM, i.e. N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, D-7711
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
using the fluorescent substrate BODIPY-FL-C12-SM, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, or D-7711
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
Leptospira interrogans 56601
P59116
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
Bacillus cereus IAM1029
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
I4DXK5
-
a ceramide is an N-acylsphingosine
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis(4-methylumbelliferyl)-phosphate + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
C6-7-nitro-2-1,3-benzoxadiazol-4-yl-sphingomyelin + H2O
?
show the reaction diagram
Q4LEU0
-
-
-
?
choline-methyl-sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
choline-methyl-sphingomyelin + H2O
?
show the reaction diagram
Q4LEU0
high activity
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
show the reaction diagram
-
-
-
-
?
L-alpha-phosphatidylinositol + H2O
?
show the reaction diagram
A6P7M9
5.63% activity compared to sphingomyelin
-
-
?
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
1-acylglycerol + choline phosphate
show the reaction diagram
-
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
show the reaction diagram
-
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
show the reaction diagram
-
-
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
show the reaction diagram
-
-
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
show the reaction diagram
-
198fold higher activity than with sphingomyelin in the absence of detergent, 580% of activity with sphingomyelin in the absence of detergent
-
?
N-dodecanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-dodecanoylsphingosine + choline phosphate
show the reaction diagram
-
-
-
?
N-hexanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-hexanoylsphingosine + choline phosphate
show the reaction diagram
-
-
-
?
N-methyl-sphingomyelin + H2O
N-methyl-N-acylsphingosine + choline phosphate
show the reaction diagram
-
-
-
-
?
N-methylsphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenylphosphorylcholine + H2O
choline phosphate + p-nitrophenol
show the reaction diagram
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
show the reaction diagram
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
show the reaction diagram
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
show the reaction diagram
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
show the reaction diagram
-
8% of activity with sphingomyelin
-
?
phosphatidylethanolamine + H2O
diacylglycerol + phosphorylethanolamine
show the reaction diagram
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
show the reaction diagram
-
low activity
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
show the reaction diagram
-
in the presence of 0.08% sodium taurodeoxycholate, in the absence of detergents an in the presence of 0.05% Nonidet P-40
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
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-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
-
-
?
platelet-inactivating 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
-
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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
Q9JJY3
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
Q9NXE4
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9BDR3
-
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
P11889
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906, Q9NY59
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9ET64
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q6UWV6
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q6UWV6
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9NY59
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9RLV9
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q4LEU0
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
D6MZJ6
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
D-erythrosphingosine or dihydroxysphingosine configuration of sphingomyelin results in a 3-5fold faster hydrolysis in comparison to a D-threo or L-erythro configuration
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
erythro-isomers of DL-trans-2-N-palmitoyl-1-O-phosphorylcholinesphingosine or dihydrosphingosine hydrolyzed faster than the threo-isomer
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
DL-erythro-N-palmitoylsphingophosphorylcholine, N-stearylsphingophosphorylcholine, N-lignocerylsphingophosphorylcholine in monomolecular layers
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
A6P7M9
100% activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
very low activity in the absence of detergent
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
SMase C causes hemolysis and thus is suspected to be a potential virulence factor
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
A-SMase in the outer epidermis is essential for basal permeability function, A-SMase activity in the lower epidermis is involved in basal permeability barrier homeostasis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
cholesterol activation of sphingomyelinase and the strong affinity of cholesterol for sphingomyelin allows the rapid, localized and self-contained production of the metabolic signal ceramide in specific microdomains
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma. Mutations of the enzyme found in colon cancer cells. IN the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
hydrolysis of sphingomyelin dispersed in diheptanoylphosphatidyl-choline. Premicellar complexes of sphingomyelinase mediate enzyme exchange for the stationary phase turnover
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the sap-like domain of human acid sphingomyelinase has activator-like functions, as well as importance as an integral part of acid spingomyelinase required for normal enzyme activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
acid SMase is involved in colonic cancer development and apoptosis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
acid sphingomyelinase is involved in ceramide signaling, which is important in the lipid raft clustering and formation of redox signaling platform in cell membranes, overview, reactive oxygen species derived from ASM/ceramide triggered lipid raft redox signaling platforms can feedback regulate the ASM activity, FasL-induced O2- may be involved in this regulatory mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
age-related increase in the activity of NSMase-2 is responsible for the interleukin-1beta hyperresponsiveness and a decrease in GSH levels, phenotype, regulation of neutral sphingomyelinase-2 by GSH in oxidative stress in aging-associated inflammation, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview, dietary SM inhibits colonic carcinogenesis by a mechanism related to SM digestion in the gut, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
changes in the initial composition and topography of mixed monolayers of sphingomyelin and ceramide modulate the sphingomyelin degradation by the enzyme, overview, the enzyme in an extracellular toxin that exhibits potent hemolytic activity against sphingomyelin-rich erythrocytes in mammals
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
degradation of sphingomyelin
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
exogenous sphingomyelinase causes impaired intestinal epithelial barrier function, Caco-2 cell monolayers are used as in vitro model for the intestinal barrier, exogenous sphingomyelinase increases transepithelial permeability and decreases transepithelial resistance at concentrations as low as 0.01 U/ml, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, and hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906, Q9NY59
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9RLV9
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
P09599
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906, Q9NY59
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview, signaling roles of nSMase2 implicated in apoptosis, inflammation, cell growth, and differentiation, and Alzheimer disease, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
secretory sphingomyelinase is upregulated in chronic heart failure, S-SMase further correlates with reduced skeletal quadriceps muscle strength as well as impaired peripheral vasodilator capacity, physiological function and parameters of S-SMase in heart tissue, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the enzyme is important in ceramide metabolism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9BDR3
the enzyme is important in the ceramide catabolism, overview
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906, Q9NY59
nSMase2 uses sphingomyelin preferentially as a substrate in vitro with no activity against lyso-PAF
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
P09599
residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
SMase shows very low activity against condensed sphingomyelin, but is active on loosely organized sphingomyelin in bilayers and monolayers, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Listeria ivanovii nSMase
Q9RLV9
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Plasmodium falciparum Honduras 1
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Streptomyces griseocarneus NBRC13471
A6P7M9
100% activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Helicobacter pylori nSMase
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Bacillus cereus nSMase
P09599
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview, residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate + ?
show the reaction diagram
-
-
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
show the reaction diagram
-
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
show the reaction diagram
-
127fold higher activity than with sphingomyelin in the absence of detergent, 980% of activity with sphingomyelin in the absence of detergent
-
?
sphingosylphosphorylcholine + H2O
sphingosine + choline phosphate
show the reaction diagram
-
25% of activity with sphingomyelin
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
show the reaction diagram
-
8% of activity with sphingomyelin
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
-
additional information
?
-
-
acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
-
-
-
additional information
?
-
-
an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
-
-
-
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
-
additional information
?
-
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
-
-
-
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
-
additional information
?
-
-
modification of the SMase/SM-synthase balance, shown in the nuclei 1 h after serum deprivation, appears specific for the early events of the apoptotic process
-
-
-
additional information
?
-
-
neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
-
-
-
additional information
?
-
-
Niemann Pick disease is an autosomal recessive disorder due to the deficit of lysosomal acid sphingomyelinase, which results in intracellular accumulation of sphingomyelin. Identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
-
-
-
additional information
?
-
-
nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
-
-
-
additional information
?
-
-
patients with atopic dermatitis show reduced activities of acid and neutral sphingomyelinase. The reduced acid sphingomyelinase activity may be partially responsible for the reduced content of stratum corneum ceramides. Reduced neutral sphingomyelinase activity may lead to changes in signal transduction, thereby regulating differentiation. The resulting reduction in involucrin could cause the reduced number of covalently bound ceramides in atopic dermatitis
-
-
-
additional information
?
-
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
-
additional information
?
-
-
spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
-
-
-
additional information
?
-
-
spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
-
-
-
additional information
?
-
-
UV light-triggered ASMase activation is essentially required for bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac
-
-
-
additional information
?
-
-
a phosphatidylcholine/sphingomyelin metabolism crosstalk which regulates the intranuclear ceramide/diacylglycerol pool exists in the chromatin structure, effect of phosphatidylcholine-specific phospholipase C activity on neutral sphingomyelinase and reverse sphingomyelin synthase, which enrich the intranuclear ceramide pool, overview
-
-
-
additional information
?
-
-
a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
-
-
-
additional information
?
-
-
acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
-
-
-
additional information
?
-
-
aging in rats causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2, NSMase-2 is both required and sufficient for the onset of IL-1beta hyperresponsiveness during aging, overview
-
-
-
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
-
additional information
?
-
-
ASMase inhibition decreases ceramide generation during ischemia/reperfusion, and attenuates serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation, overview, the enzyme is involved in hepatic ischemia/reperfusion damage, ceramide generated from ASMase plays a key role in I/R-induced liver damage, molecular mechanisms, overview
-
-
-
additional information
?
-
-
common polymorphisms of the SMPD1 gene occur in Niemann-Pick disease type A and B, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
-
-
-
additional information
?
-
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
Q9RLV9
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
P09599
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
exogenous acidic sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
-
additional information
?
-
-
exogenous neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
-
additional information
?
-
Q9BDR3
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
-
additional information
?
-
-
exposure to the NO donors promotes an increase in the protein-protein interaction between acidic sphingomyelinase and caspase-3, with aSMase sequestering caspase-3 and preventing its cleavage and inhibiting apoptosis, overview
-
-
-
additional information
?
-
-
many signaling molecules involved in the pathogenesis of intestinal epithelial barrier, such as TNF-alpha or IFN-gamma, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases
-
-
-
additional information
?
-
-
neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors are essentially involved in endothelial nitric oxide synthase activation by tumor necrosis factor alpha, regulation of the pathway, overview
-
-
-
additional information
?
-
-
neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
-
-
-
additional information
?
-
-
neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats and is a key event in glutathione repletion, overview
-
-
-
additional information
?
-
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, different oxidants modulate different enzymes of the ceramide generating machinery to induce apoptosis in airway epithelial cells, overview
-
-
-
additional information
?
-
-
role for nSMase2 in pro-inflammatory responses induced by TNF-alpha as a regulator of adhesion proteins, both p38-alpha MAPK and nSMase2 are involved in the TNF-alpha-stimulated up-regulation of the adhesion proteins vascular cell adhesion molecule-1 and intercellular adhesion molecule-1
-
-
-
additional information
?
-
-
sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion at a step in the fusion process after CD4 engagement, but sphingomyelinase treatment of cells does not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis, and furthermore, sphingomyelinase treatment does not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, Smase treatment does not influence Triton X-100 extraction of HIV-1 receptor proteins, overview
-
-
-
additional information
?
-
Q9RLV9
the enzyme is a virulence factor
-
-
-
additional information
?
-
-
the enzyme is involved in sphingomyelin digestion
-
-
-
additional information
?
-
-
structural-functional properties of its carboxyl-terminus, amino acids 462-629, the carboxyl-terminus of the ASM is crucial for its protein structure, which in turns dictates the enzymatic function and secretion, overview
-
-
-
additional information
?
-
Q6UWV6
wild-type alkaline sphingomyelinase inhibits colonic tumorigenesis, while enzyme deficiency or aberrant enzyme forms are associated with human liver tumorigenesis, the enzyme activity is increased in cholestatic liver disease excluding primary sclerosing cholangitis, overview
-
-
-
additional information
?
-
-
ASM is necessary for stress-induced cell death
-
-
-
additional information
?
-
-
ASMase activity is required for an efficient fusion of late phagosomes with lysosomes including the efficient transfer of lysosomal hydrolases into phagosomes containing Listeria monocytogenes
-
-
-
additional information
?
-
Q4LEU0
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
-
additional information
?
-
-
Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
-
-
-
additional information
?
-
-
SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
-
-
-
additional information
?
-
-
Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
-
-
-
additional information
?
-
-
Src kinase-dependent phosphorylation of p38 MAPK is involved in P2X7-induced A-SMase activation, A-SMase mediates ATP receptor P2X7R-dependent microparticle shedding and P2X7-dependent IL-1beta release
-
-
-
additional information
?
-
-
the specific ligand binding activity of the serotonin1A receptor in membranes isolated from CHO-5-HT1AR cells is increased upon sphingomyelinase treatment (25 or 50 mU/ml) for 90 min in DMEM/F-12 medium under serum free condition
-
-
-
additional information
?
-
-
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, PlcHR2 toxin from Pseudomonas aeruginosa is an enzyme with both phospholipase C and sphingomyelinase activities, PlcHR2 hydrolyzes phosphatidylcholine and sphingomyelin at similar rates, but other phospholipids are cleaved at much lower rates, if at all
-
-
-
additional information
?
-
Q4LEU0
the enzyme has no activity against choline-methyl-phosphatidylcholine
-
-
-
additional information
?
-
A6P7M9
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
-
additional information
?
-
-
establishment of a sensitive quantitative assay method using the fluorescent substrate BODIPY-FL-C12-SM, i.e. N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, D-7711
-
-
-
additional information
?
-
-
establishment of a sensitive quantitative assay method using the fluorescent substrate BODIPY-FL-C12-SM, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, or D-7711
-
-
-
additional information
?
-
I4DXK5
substrate specificity, the enzyme is highly sphingomyelin-specific, it may not have sphingomyelinase D activity, because it does not hydrolyze the ester linkage between ceramide phosphate and choline. Of the phospholipids tested, the enzyme hydrolyzes only the ester linkage between ceramide and phosphocholine and has no activity toward phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine and phosphatidylinositol
-
-
-
additional information
?
-
Bacillus cereus, Bacillus cereus IAM1029
-
the enzyme's beta-hairpin site directly binds to gangliosides, especially ganglioside GM3, i,e, NeuAca2-3Galbeta1-4Glcbeta1-1ceramide through a carbohydrate moiety. Binding response of the enzyme to liposomes containing GM3 is about 15fold higher than that to liposomes lacking GM3. Residues Trp-284 and Phe-285 in the beta-hairpin play an important role in the interaction with GM3
-
-
-
additional information
?
-
Listeria ivanovii nSMase
Q9RLV9
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
I4DXK5
substrate specificity, the enzyme is highly sphingomyelin-specific, it may not have sphingomyelinase D activity, because it does not hydrolyze the ester linkage between ceramide phosphate and choline. Of the phospholipids tested, the enzyme hydrolyzes only the ester linkage between ceramide and phosphocholine and has no activity toward phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine and phosphatidylinositol
-
-
-
additional information
?
-
Streptomyces griseocarneus NBRC13471
A6P7M9
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
-
additional information
?
-
Rattus norvegicus Fischer 344
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
-
additional information
?
-
Helicobacter pylori nSMase
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
Bacillus cereus nSMase
P09599
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
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + 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
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
Q9JJY3
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
I4DXK5
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
P59116
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
E9LUE7, E9LUE8, E9LUE9, P17405
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
-
-
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
show the reaction diagram
Leptospira interrogans 56601
P59116
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
Bacillus cereus IAM1029
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
show the reaction diagram
I4DXK5
-
a ceramide is an N-acylsphingosine
-
?
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
show the reaction diagram
-
low activity
-
?
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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9JJY3
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + 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
O60906
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9ET64
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q6UWV6
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q6UWV6
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9NY59
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
SMase C causes hemolysis and thus is suspected to be a potential virulence factor
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
A-SMase in the outer epidermis is essential for basal permeability function, A-SMase activity in the lower epidermis is involved in basal permeability barrier homeostasis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
cholesterol activation of sphingomyelinase and the strong affinity of cholesterol for sphingomyelin allows the rapid, localized and self-contained production of the metabolic signal ceramide in specific microdomains
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma. Mutations of the enzyme found in colon cancer cells. IN the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
acid SMase is involved in colonic cancer development and apoptosis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
acid sphingomyelinase is involved in ceramide signaling, which is important in the lipid raft clustering and formation of redox signaling platform in cell membranes, overview, reactive oxygen species derived from ASM/ceramide triggered lipid raft redox signaling platforms can feedback regulate the ASM activity, FasL-induced O2- may be involved in this regulatory mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
age-related increase in the activity of NSMase-2 is responsible for the interleukin-1beta hyperresponsiveness and a decrease in GSH levels, phenotype, regulation of neutral sphingomyelinase-2 by GSH in oxidative stress in aging-associated inflammation, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview, dietary SM inhibits colonic carcinogenesis by a mechanism related to SM digestion in the gut, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
changes in the initial composition and topography of mixed monolayers of sphingomyelin and ceramide modulate the sphingomyelin degradation by the enzyme, overview, the enzyme in an extracellular toxin that exhibits potent hemolytic activity against sphingomyelin-rich erythrocytes in mammals
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
degradation of sphingomyelin
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
exogenous sphingomyelinase causes impaired intestinal epithelial barrier function, Caco-2 cell monolayers are used as in vitro model for the intestinal barrier, exogenous sphingomyelinase increases transepithelial permeability and decreases transepithelial resistance at concentrations as low as 0.01 U/ml, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, and hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906, Q9NY59
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9RLV9
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
P09599
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
O60906, Q9NY59
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview, signaling roles of nSMase2 implicated in apoptosis, inflammation, cell growth, and differentiation, and Alzheimer disease, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
secretory sphingomyelinase is upregulated in chronic heart failure, S-SMase further correlates with reduced skeletal quadriceps muscle strength as well as impaired peripheral vasodilator capacity, physiological function and parameters of S-SMase in heart tissue, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the enzyme is important in ceramide metabolism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Q9BDR3
the enzyme is important in the ceramide catabolism, overview
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
-
the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
?
show the reaction diagram
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Listeria ivanovii nSMase
Q9RLV9
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Plasmodium falciparum Honduras 1
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Helicobacter pylori nSMase
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
show the reaction diagram
Bacillus cereus nSMase
P09599
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
a sphingomyelin + H2O
a ceramide + choline phosphate
show the reaction diagram
Clostridium perfringens 8-6
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
-
additional information
?
-
-
acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
-
-
-
additional information
?
-
-
an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
-
-
-
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
-
additional information
?
-
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
-
-
-
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
-
additional information
?
-
-
modification of the SMase/SM-synthase balance, shown in the nuclei 1 h after serum deprivation, appears specific for the early events of the apoptotic process
-
-
-
additional information
?
-
-
neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
-
-
-
additional information
?
-
-
Niemann Pick disease is an autosomal recessive disorder due to the deficit of lysosomal acid sphingomyelinase, which results in intracellular accumulation of sphingomyelin. Identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
-
-
-
additional information
?
-
-
nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
-
-
-
additional information
?
-
-
patients with atopic dermatitis show reduced activities of acid and neutral sphingomyelinase. The reduced acid sphingomyelinase activity may be partially responsible for the reduced content of stratum corneum ceramides. Reduced neutral sphingomyelinase activity may lead to changes in signal transduction, thereby regulating differentiation. The resulting reduction in involucrin could cause the reduced number of covalently bound ceramides in atopic dermatitis
-
-
-
additional information
?
-
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
-
additional information
?
-
-
spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
-
-
-
additional information
?
-
-
spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
-
-
-
additional information
?
-
-
UV light-triggered ASMase activation is essentially required for bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac
-
-
-
additional information
?
-
-
a phosphatidylcholine/sphingomyelin metabolism crosstalk which regulates the intranuclear ceramide/diacylglycerol pool exists in the chromatin structure, effect of phosphatidylcholine-specific phospholipase C activity on neutral sphingomyelinase and reverse sphingomyelin synthase, which enrich the intranuclear ceramide pool, overview
-
-
-
additional information
?
-
-
a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
-
-
-
additional information
?
-
-
acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
-
-
-
additional information
?
-
-
aging in rats causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2, NSMase-2 is both required and sufficient for the onset of IL-1beta hyperresponsiveness during aging, overview
-
-
-
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
-
additional information
?
-
-
ASMase inhibition decreases ceramide generation during ischemia/reperfusion, and attenuates serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation, overview, the enzyme is involved in hepatic ischemia/reperfusion damage, ceramide generated from ASMase plays a key role in I/R-induced liver damage, molecular mechanisms, overview
-
-
-
additional information
?
-
-
common polymorphisms of the SMPD1 gene occur in Niemann-Pick disease type A and B, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
-
-
-
additional information
?
-
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
Q9RLV9
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
P09599
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
exogenous acidic sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
-
additional information
?
-
-
exogenous neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
-
additional information
?
-
Q9BDR3
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
-
additional information
?
-
-
exposure to the NO donors promotes an increase in the protein-protein interaction between acidic sphingomyelinase and caspase-3, with aSMase sequestering caspase-3 and preventing its cleavage and inhibiting apoptosis, overview
-
-
-
additional information
?
-
-
many signaling molecules involved in the pathogenesis of intestinal epithelial barrier, such as TNF-alpha or IFN-gamma, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases
-
-
-
additional information
?
-
-
neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors are essentially involved in endothelial nitric oxide synthase activation by tumor necrosis factor alpha, regulation of the pathway, overview
-
-
-
additional information
?
-
-
neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
-
-
-
additional information
?
-
-
neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats and is a key event in glutathione repletion, overview
-
-
-
additional information
?
-
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, different oxidants modulate different enzymes of the ceramide generating machinery to induce apoptosis in airway epithelial cells, overview
-
-
-
additional information
?
-
-
role for nSMase2 in pro-inflammatory responses induced by TNF-alpha as a regulator of adhesion proteins, both p38-alpha MAPK and nSMase2 are involved in the TNF-alpha-stimulated up-regulation of the adhesion proteins vascular cell adhesion molecule-1 and intercellular adhesion molecule-1
-
-
-
additional information
?
-
-
sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion at a step in the fusion process after CD4 engagement, but sphingomyelinase treatment of cells does not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis, and furthermore, sphingomyelinase treatment does not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, Smase treatment does not influence Triton X-100 extraction of HIV-1 receptor proteins, overview
-
-
-
additional information
?
-
Q9RLV9
the enzyme is a virulence factor
-
-
-
additional information
?
-
-
the enzyme is involved in sphingomyelin digestion
-
-
-
additional information
?
-
-
ASM is necessary for stress-induced cell death
-
-
-
additional information
?
-
-
ASMase activity is required for an efficient fusion of late phagosomes with lysosomes including the efficient transfer of lysosomal hydrolases into phagosomes containing Listeria monocytogenes
-
-
-
additional information
?
-
Q4LEU0
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
-
additional information
?
-
-
Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
-
-
-
additional information
?
-
-
SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
-
-
-
additional information
?
-
-
Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
-
-
-
additional information
?
-
-
Src kinase-dependent phosphorylation of p38 MAPK is involved in P2X7-induced A-SMase activation, A-SMase mediates ATP receptor P2X7R-dependent microparticle shedding and P2X7-dependent IL-1beta release
-
-
-
additional information
?
-
-
the specific ligand binding activity of the serotonin1A receptor in membranes isolated from CHO-5-HT1AR cells is increased upon sphingomyelinase treatment (25 or 50 mU/ml) for 90 min in DMEM/F-12 medium under serum free condition
-
-
-
additional information
?
-
-
The sphingomyelinase, but not the phospholipase C activity, is essential for induction of hot-cold hemolysis in human erythrocytes, that contain both phosphatidylcholine and sphingomyelin but also in goat erythrocytes, which lack phosphatidylcholine, however, in horse erythrocytes, with a large proportion of phosphatidylcholine and almost no sphingomyelin, hot-cold hemolysis induced by PlcHR2 is not observed, overview. Sphingomyelinase activity gives rise to the formation of ceramide-rich, rigid membrane domains that are resistant to Triton X-100 solubilization
-
-
-
additional information
?
-
Listeria ivanovii nSMase
Q9RLV9
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
Rattus norvegicus Fischer 344
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
-
additional information
?
-
Helicobacter pylori nSMase
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
Bacillus cereus nSMase
P09599
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
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
slight activation when water-soluble substrates are used
Ca2+
-
lysosomal enzyme, stimulation at pH 5-7.5
Ca2+
-
partly restores the EDTA-inhibited enzyme activity
Ca2+
-
-
Ca2+
-
activation of hemolysis at 2 mM, strong inhibition at 10 mM
Ca2+
P11889
Km: 0.0191 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Ca2+
-
plays a role in enzyme regulation by non-substrate lipids
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+
Ca2+
I4DXK5
slightly activates, Km is 1.40 mM
Cd2+
-
-
Co2+
-
-
Co2+
-
lysosomal enzyme, stimulation at pH 5-7.5
Co2+
-
can replace Mg2+
Co2+
-
can replace Mg2+, 50% activation at 0.0015 mM
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+
P11889
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
Co2+
-
required
Co2+
-
activates
Co2+
I4DXK5
activates, Km is 1.46 mM
Cu2+
-
6fold increase in activity at 0.1 mM
Cu2+
A6P7M9
107% activity at 1 mM Mg2+
Fe2+
-
-
Fe2+
A6P7M9
104% activity at 1 mM Mg2+
KCl
-
1 M, 3fold activation
KCl
Q9ET64
required for full activity
Mg2+
-
activation of plasma membrane and microsomal enzyme; lysosomal enzyme, stimulation at pH 5-7.5
Mg2+
-
causes basal activation, reverses EDTA inhibition
Mg2+
-
5fold activation of enzyme A and B at pH 7.5
Mg2+
-
activates the 92000 Da isoform but not the 53000 Da one
Mg2+
-
dependent
Mg2+
-
dependent
Mg2+
-
required for activity, half-maximal activation at 1 mM
Mg2+
-
required for activity, maximal activity at 8-16 mM, Km at 3 mM
Mg2+
-
absolutely required for activity
Mg2+
-
required for activity, Glu53 act as a ligand for the essential Mg2+
Mg2+
-
required for activity
Mg2+
-
5 mM, activation
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+
-
required for activity, maximal activation at 2-5 mM
Mg2+
-
required for activity, approx. 3fold activation at 0.1-0.5 mM
Mg2+
-
required for activity, maximal activation at 5 mM
Mg2+
-
required for activity
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+
Q9NY59
required for activity
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+
-
required
Mg2+
-
dependent on
Mg2+
Q9NXE4
5 mM, stimulates
Mg2+
P11889
Km: 0.0161 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Mg2+
P09599
required by N-SMase for activity, residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
Mg2+
-
required by N-SMase for activity
Mg2+
O60906, Q9NY59
required by nSMase1 for activity; required by N-SMase for activity
Mg2+
Q9RLV9
required by N-SMase for activity
Mg2+
-
required by N-SMase for activity
Mg2+
-
nSMase2 is a Mg2+-dependent neutral sphingomyelinase
Mg2+
-
neutral SMase
Mg2+
-
dependent on, best at 3 mM
Mg2+
-
dependent on, ASMase
Mg2+
-
NSMase is dependent on Mg2+
Mg2+
-
NSMase activity depends on Mg2+
Mg2+
Q4LEU0
dependent on
Mg2+
-
dependent on
Mg2+
-
dependent on
Mg2+
D6MZJ6
absolute requirement for cations such as Mg2+ and Mn2+
Mg2+
A6P7M9
required, 100% activity at 2.5-10 mM Mg2+
Mg2+
-
required
Mg2+
-
required
Mg2+
-
required
Mg2+
-
required by N-SMase
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+
Q9JJY3
required
Mg2+
Q8IUN0
activates
Mg2+
I4DXK5
activates, Km is 1.29 mM
Mg2+
P59116
dependent on, isozyme Sph2 is unique and possesses the Mg2+-binding Glu53 residue in the metal-binding site
Mn2+
-
-
Mn2+
-
activation of plasma membrane and microsomal enzyme; lysosomal enzyme, stimulation at pH 5-7.5
Mn2+
-
-
Mn2+
-
can replace Mg2+, Km at 2.5 mM
Mn2+
-
can replace Mg2+
Mn2+
-
5 mM, activation
Mn2+
-
can replace Mg2+, 50% activation at 0.00087 mM
Mn2+
-
can replace Mg2+, maximal activity at 0.5 mM, inhibition above
Mn2+
-
can replace Mg2+, maximal activation at 1-2 mM, slight inhibition above
Mn2+
Q9NY59
can replace Mn2+
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+
Q9NXE4
5 mM, stimulates
Mn2+
P11889
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+
D6MZJ6
absolute requirement for cations such as Mg2+ and Mn2+
Mn2+
A6P7M9
required, 100% activity at 1 mM Mg2+
Mn2+
-
required
Ni2+
-
-
Sr2+
P11889
Km: 0.018 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Sr2+
I4DXK5
slightly activates, Km is 2.42 mM
Zn2+
-
-
Zn2+
-
partly restores the EDTA-inhibited enzyme activity
Zn2+
-
slight activation at 4 mM, Km at 2 mM
Zn2+
-
5fold increase in activity at 0.1 mM
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; 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+
-
activates the alk-SMase activity with platelet-inactivating factor, mutation of the metal binding site abolishes the enzyme activity
Zn2+
-
0.1-0.25 mM stimulates hydrolysis of platelet-activating factor; activates the alk-SMase activity with platelet-inactivating factor, mutation of the metal binding site of alk-SMase abolishes the enzyme activity
Zn2+
-
Zn2+-dependent sphingomyelinase acid activity is much higher than Zn2+ independent isoform activity in both fetal and mother's blood
Zn2+
-
most of the secreted activity requires Zn2+ for full activity
Zn2+
P09599
Zn2+ binding to the high-affinity site activates the enzyme and, conversely, binding to the low-affinity site inhibits the enzyme
Zn2+
-
aSMase is processed from a 75-kDa, Zn2+-activated proenzyme to a mature 65 kDa, Zn2+-independent L-SMase
Zn2+
-
required by the secreted enzyme form
Zn2+
Q8IUN0
activates
Zn2+
-
required for activity, best at 0.5-1 mM, inhibitory above 10 mM
Mn2+
I4DXK5
activates, most effective divalent metal ion, Km is 0.94 mM
additional information
P09599
metal binding structure, overview
additional information
Q9RLV9
metal binding structure, overview
additional information
-
Mg2+, Mn2+, Ca2+ and Zn2+, or Ca2+ have no significant effect on the activity
additional information
D6MZJ6
Ca2+, Co2+, Fe2+, or Zn2+ do not support MA-nSMase activity
additional information
A6P7M9
not stimulated by Ca2+, CO2+, and Fe3+; the order of potency to enhance the activity is Zn2+>Mn2+>Cu2+>Fe2+
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
-
the enzyme is dependent on divalent metal ions
additional information
I4DXK5
central metal-binding site residues N77, E119, D265, N267, D374, and H375 are completely conserved in the enzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1-aminodecane-1,1-diyl)bis(phosphonic acid)
-
a substrate analogue inhibitor of aSMase
1,10-phenanthroline
-
-
1,2-dioleoyl-sn-glycerol
-
approx. 40% inhibition at 3.2 mM
1,2-distearoyl-rac-glycerol
-
approx. 30% inhibition at 3.2 mM
1,3,5-tri-O-dodecylsulfonyl-D_myo-inositol
-
-
1,3,5-tri-O-ethylsulfonyl-D-myo-inositol
-
-
1,3,5-tri-O-methylsulfonyl-D-myo-inositol
-
-
1,3,5-tri-O-octylsulfonyl-D-myo-inositol
-
-
1-O-dodecylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-ethylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-hexylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-methylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-O-octylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
-
1-oleoyl-rac-glycerol
-
slight stimulation below 0.8 mM, approx. 50% inhibition at 3.2 mM
1-stearoyl-rac-glycerol
-
slight stimulation below 0.8 mM, approx. 10% inhibition at 3.2 mM
2'-AMP
-
mixture with 3'-AMP
27-Hydroxycholesterol
-
inhibition of acid sphingomyelinase; inhibition of neutral sphingomyelinase occurs at a posttranscriptional level
3',5'-cAMP
-
IC50: above 0.5 mM
3'-AMP
-
mixture with 2'-AMP
3-acetyl-11-keto-beta-boswellic acid
-
62% inhibition of acid SMase at 0.1 mM
3-O-methylsphingomyelin
-
-
-
3-O-methylsphingomyelin
-
-
-
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
-
-
3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate
-
inhibits taurocholate-induced activation
3-[benzyl(tert-butyl)amino]-1-(4-nitrophenyl)propan-1-one
-
-
5'-AMP
-
-
5'-AMP
-
lysosomes
5-adenoylimino phosphate
-
IC50: above 0.5 mM
6-O-dodecylsulfonyl-D-glucose 2,4-bisphosphate
-
-
6-O-ethylsulfonyl-D-glucose 2,4-bisphosphate
-
-
6-O-hexylsulfonyl-D-glucose 2,4-bisphosphate
-
-
6-O-octylsulfonyl-D-glucose 2,4-bisphosphate
-
-
AD2765
-
a substrate analogue inhibitor of aSMase
adenine-9-beta-D-arabinofuranoside 5'-monophosphate
-
-
adeno 5'-diphosphate
-
IC50: above 0.5 mM
adeno-2',3'-cyclic phospho 5'-monophosphate
-
IC50: 0.2 mM
adeno-2',3'-cyclic phospho 5'-phosphosulfate
-
IC50: 0.5 mM
adenosine 3',5'-diphosphate
-
-
adenosine 5'-monophosphate
-
periodate-oxidized and an isomer with arabinose instead of ribose as sugar component
Adenosine 5'-O-thiomonosulfate
-
-
adenosine 5'-phosphosulfate
-
-
ADP
-
IC50: 0.3 mM
alpha-mangostin
-
a xanthone from the bark of Garcinia speciosa
amitriptyline
-
performs indirect inhibition of aSMase
amitriptyline
-
-
amitriptyline
-
specific inhibitor
AMP
-
-
AMP
-
lysosomes
AMP
-
IC50: 0.08 mM, non-competitive inhibition
arachidonic acid
-
slight stimulation below 0.8 mM, approx. 50% inhibition at 3.2 mM
ATP
-
IC50: 0.8 mM
BeF2
P09599
an unusual phosphate analogue
Brij 56
-
-
C11AG
-
inhibits N-SMases in T-cells and macrophages
Ca2+
-
when sphingomyelin as substrate with Triton X-100 is used, competitive inhibitor against Mg2+
Ca2+
-
completely inhibited at 5 mM CaCl2
Ca2+
-
slight
Ca2+
-
-
Ca2+
-
strong inhibition of hemolysis at 10 mM
Ca2+
-
6.9 mM, 50% inhibitiion
Ca2+
-
0.1 mM, 60% inhibition of Mg2+-activated N-SMase
Ca2+
P09599
-
Ca2+
P59116
inhibits the hemolytic enzyme activity
ceramide
-
-
ceramide
-
23% inhibition
ceramide
-
strong inhibition in the presence of 0.4 mM linoleic acid
ceramide
Q9BDR3
product feedback inhibition; product feedback inhibition
ceramide
-
feedback inhibition
Cetylpyridinium chloride
-
-
Cetyltrimethylammonium bromide
-
-
Cetyltrimethylammonium bromide
-
-
CHAPS
-
hydrolysis of sphingomyelin and platelet-activating factor
CHAPS
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
Chelating agents
-
-
Chloroquine
-
diphosphate salt, 50% inhibition at 5 mM
chlorprothixene
-
-
cholate
-
-
cholesterol
-
strong inhibition in the presence of 0.4 mM linoleic acid
cis, cis-cyclohexane 1,3,5-trisphosphate
-
barely inhibits aSMase even at a 0.1 mM concentration
cowanin
-
a xanthone from the bark of Garcinia speciosa
cowanol
-
a xanthone from the bark of Garcinia speciosa
Cu2+
-
5 mM, complete inhibition
Cu2+
-
0.0079 mM, 50% inhibitiion
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
-
-
D609
-
48% inhibition of the enzyme in chromain after 30 min of treatment, no inhibition by D609 in the nuclear membrane
D609
-
nonspecific sphingomyelinase inhibitor
deoxycholate
-
-
deoxycholate
Q9JJY3
inhibits almost 90% of the activity at 3 mM
desipramine
-
-
desipramine
-
inhibits acidic SMase
desipramine
-
inhibits the acid SMase, and lipopolysaccharide induction of interleukin-8 synthesis in vivo
desipramine
-
performs indirect inhibition of aSMase
desipramine
-
inhibits the processed lysosomal L-SMase
desipramine
-
specific inhibitor
Diamide
Q9JJY3
-
dichloroisocoumarin
-
-
dithioerythritol
-
-
dithiothreitol
-
-
dithiothreitol
-
-
dithiothreitol
-
10 mM, 25% inhibition
dithiothreitol
A6P7M9
33.1% residual activity at 2 mM
EDTA
-
-
EDTA
-
complete inhibition at 0.25 mM
EDTA
-
20 mM, complete inhibition
EDTA
-
5 mM, complete inhibition, subsequent addition of Mn2+, Mg2+ or Ca2+ restores activity to 300% of that before EDTA treatment
EDTA
-
10 mM, 95% inhibition
EDTA
Q9NY59
5 mM, complete inhibition, activity is comletely restored by the subsequent addition of 10 mM Mg2+ or Mn2+
EDTA
-
alk-SMase activity with platelet-inactivating factor
EDTA
-
alk-SMase activity with platelet-inactivating factor; inhibits hydrolysis of platelet-activating factor, no effect on hydrolysis of sphingomyelin
EDTA
A6P7M9
complete inhibition at 2 mM
EDTA
-
inactivation
fatty acids
-
-
Fe2+
-
-
Fe3+
-
-
ganglioside GT1b
-
-
gangliosides
-
particularly monogangilosides
-
glutathione
-
-
glutathione
-
-
glutathione
-
then oxidized
glutathione
-
-
glutathione
-
3 mM, 95% inhibition
glutathione
-
0.2 mM, almost complete inhibition
GSH
-
inhibition of all T-mSMase and S-mSMase isoforms above 2.5 mM
GSH
-
a potent inhibitor of liver NSMase-2 activity
GW4869
-
0.015 mM, 40% inhibition, 0.045 mM, 70% inhibition
GW4869
O60906, Q9NY59
specific inhibition
GW4869
-
noncompetitive
GW4869
-
inhibits the neutral SMase, and lipopolysaccharide induction of interleukin-8 synthesis in vivo
GW4869
-
inhibited by 0.001-0.1 mM
Hg2+
-
-
Hg2+
-
plasma membrane and microsomes
Hg2+
-
5 mM, complete inhibition
hydrogen peroxide
Q9JJY3
-
imipramine
-
ASMase inhibitor
imipramine
-
-
imipramine
-
performs indirect inhibition of aSMase
imipramine
-
specific inhibitor
lecithin
-
-
linoleic acid
-
slight stimulation below 0.8 mM, approx. 45% inhibition at 3.2 mM
linolenic acid
-
stimulation below 0.8 mM, approx. 15% inhibition at 3.2 mM
lysophosphatidic acid
-
IC50: 0.04 mM
Lysophospholipids
-
-
-
mannose 6-phosphate
-
Niemann-Pick disease fibroblasts
manumycin A
-
-
Mg2+
-
lysosomal enzyme, inhibition at below pH 4.8
Mg2+
-
slight inhibitory at higher concentrations
Mn2+
-
above 0.5 mM
myo-inositol 1,3,5-trisphosphate
-
-
myo-Inositol 3,5-bisphosphate
-
-
n-butanol
-
plasma membrane
N-tosyl-L-phenylalanyl chloromethyl ketone
-
-
N-[(2S,3R,4E)-1-(2,2'-bipyridin-6-ylmethoxy)-3-hydroxyoctadec-4-en-2-yl]hexanamide [Mg2+]
-
i.e. RY221B-a, synthesis, binding simulations and docking study, overview
N-[(2S,3R,4E)-3-(2,2'-bipyridin-6-ylmethoxy)-1-hydroxyoctadec-4-en-2-yl]hexanamide
-
i.e. RY221B-b, synthesis, binding simulations and docking study, overview
NAD+
-
IC50: above 0.5 mM
NADP+
-
IC50: above 0.5 mM
Ni2+
-
-
Ni2+
-
5 mM, complete inhibition
oleic acid
-
stimulation below 0.8 mM, approx. 10% inhibition at 3.2 mM
oxidized glutathione
O60906, Q9NY59
reversible inhibition of nSMase1
oxidized glutathione
Q9JJY3
-
p-chloromercuribenzoate
-
plasma membrane and microsomes
p-hydroxymercuribenzoate
-
slight
palmitate
-
a non-substrate lipid belonging to the phospholipase A2 pathway
Pb2+
-
-
peroxynitrite
O60906, Q9NY59
irreversible inhibition of nSMase1
phenylmethylsulfonyl fluoride
A6P7M9
70.3% residual activity at 2 mM
phosphate
-
-
phosphate
-
-
phosphate
-
IC50: 10 mM, non-competitive inhibition
phosphatidyl inositol 3,5-bisphosphate
-
potent selective acid sphingomyelinase inhibitor
phosphatidyl inositol-3,5-bisphosphate
-
-
phosphatidyl-myo-inositol 3,4,5-triphosphate
-
IC50: 0.003 mM
phosphatidyl-myo-inositol 4,5-diphosphate
-
IC50: 0.25 mM
phosphatidylcholine
-
IC50: 2 mM
phosphatidylinositol
-
-
phosphatidylinositol
-
-
phosphatidylinositol 3,5-bisphosphate
-
potent inhibitor
phosphatidylinositol 4',5'-bisphosphate
-
-
phosphatidylinositol-4,5-bisphosphate
-
-
phosphatidylserine
-
-
phosphorylcholine
-
23% inhibition
phosphorylcholine
-
-
phytosphingosine
-
-
Platelet-activating factor
-
hydrolysis of sphingomyelin
platelet-inactivating factor
-
competitive inhibition of sphingomyelin hydrolysis
-
pronase E
-
reduction of stimulation of the two activator proteins
-
reactive oxygen species
O60906, Q9NY59
reversible inhibition of nSMase1
-
scyphostatin
-
0.005 mM, 50% inhibition, complete inhibition at 0.033 mM
scyphostatin
-
0.02 mM, complete inhibition
scyphostatin
-
specific inhibitor of neutral sphingomyelinase, prevents mechanoactivation of neutral sphingomyelinase
scyphostatin
Q9NXE4
-
scyphostatin
-
isolated from Discomycetes, specifically inhibits N-SMases
scyphostatin
-
inhibition of NSMase activity in hepatocytes from aged rats using leads to reversion to the young phenotype of IL-1beta response
scyphostatin
-
specific inhibitor of nSMase
SDS
A6P7M9
67.7% residual activity at 2 mM
sphingomyelin
-
strong competitive inhibition of platelet-inactivating factor hydrolysis
sphingomyelin
-
hydrolysis of platelet-activating factor; strong competitive inhibition of platelet-inactivating factor hydrolysis
sphingosine
-
-
sphingosylphosphocholine
-
-
Sr2+
P09599
-
SR33557
-
the calcium channel inhibitor performs indirect inhibition of aSMase
stearic acid
-
slight stimulation below 0.8 mM, approx. 10% inhibition at 3.2 mM
sulphydryl reagents
-
-
taurocholate
-
in presence of Triton X-100
triflupromazine
-
-
triolein
-
approx. 30% inhibition at 3.2 mM
tristearin
-
approx. 35% inhibition at 3.2 mM
Triton X-100
-
slight inhibition with 2-hexadecynoylamino-4-nitrophenylphosphorylcholine
Triton X-100
-
dose dependent, alkaline sphingomyelinase
Triton X-100
-
-
Triton X-100
-
-
Triton X-100
-
-
Triton X-100
-
hydrolysis of sphingomyelin and platelet-activating factor
Triton X-100
-
CHAPS and Triton X-100 that are commonly used in acid and neutral SMase assays, do not stimulate but rather strongly inhibit the bile salt-induced activation of Alk-SMase
Triton X-100
-
strong inhibition in the presence of 0.05-0.2% Triton X-100
Triton X-100
Q9JJY3
inhibits almost 90% of the activity at 0.1%
Trypsin
-
inactivation in pancreas, liver, duodenum but not in intestine, acid sphingomyelinase
-
Zn2+
-
-
Zn2+
-
-
Zn2+
-
5 mM, complete inhibition
Zn2+
-
0.0042 mM, 50% inhibitiion, higher concentrations of Mg2+ slighty restore activity
Zn2+
-
almost complete inhibition of Mg2+-activated N-SMase
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+
-
0.1-0.25 mM inhibits hydrolysis of platelet-activating factor, concentrations above 0.25 mM inhibit hydrolysis of sphingomyelin and platelet-activating factor
Zn2+
P09599
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+
-
required for activity, best at 0.5-1 mM, inhibitory above 10 mM
[(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
-
-
Mn2+
-
slight inhibition above 2 mM
additional information
-
-
-
additional information
-
-
-
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
-
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
-
bile diversion reduces the alkaline SMase activity by 85% in the small intestinal content and 68% in the faeces, but not in the intestinal mucosa
-
additional information
-
Alk-SMase is resistant to trypsin digestion
-
additional information
-
pentoxifylline treatment preventsTNFupregulation and ASMase activation
-
additional information
-
Salmonella enterica serovar typhimurium infection reduces ASM activity, overview
-
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
-
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
-
ceramidase inhibits hot-cold hemolysis induced by PlcHRx2, Cer is essential in the mechanism of hot-cold hemolysis
-
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
-
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
-
EDTA or EGTA in the reaction mixture have no effect on the basal activity
-
additional information
A6P7M9
the enzyme is not inhibited by mercaptoethanol and iodoacetamide
-
additional information
-
not inhibited by fumonisin B1
-
additional information
-
3-acetyl-11-keto-beta-boswellic acid does not inhibit neutral or alkaline SMase activity
-
additional information
-
no effect on activity by monosialic ganglioside GM3 and phospholipids
-
additional information
-
neuraminidase from Clostridium perfringens inhibits the binding of the enzyme to mouse peritoneal macrophages
-
additional information
Q9JJY3
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-alpha,25-dihydroxyvitamin D3
-
-
1-oleoyl-rac-glycerol
-
approx. 20% stimulation at 0.4-0.8 mM, inhibition above
1-stearoyl-rac-glycerol
-
approx. 10% stimulation at 0.8 mM, inhibition above
2-mercaptoethanol
-
-
2-mercaptoethanol
Q9JJY3
activates in vivo by severalfold
Activator proteins
-
from human spleen, two forms of
-
Albumin
-
20% activation of enzyme A and B
-
Anionic phospholipids
-
APLs, the enzymatic activity of nSMase2 is dependent on anionic phospholipids, structural requirements for APL-selective binding of nSMase2, overview. nSMase2 interacts specifically and directly with several APLs, including phosphatidylserine and phosphatidic acid. Identification of two discrete APL binding domains in the N terminus of nSMase2, the nSMase2 N-terminal domain is essential for nSMase interaction with APLs
-
arachidonic acid
-
-
arachidonic acid
-
approx. 3fold activation at 0.5 mM
arachidonic acid
-
approx. 20% stimulation at 0.4-0.8 mM, inhibition above
bile salt
-
required for activity
bile salt
-
dependent on, particularly taurocholate and taurochenodeoxycholate
Bile salts
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
cardiolipin
-
anionic phospholipids required for activity, maximal activation at 1 mM, 21% of activation with phosphatidylserine
cardiolipin
-
0.1 mM, approx. 40fold activation
cardiolipin
D6MZJ6
enzymatic activity is induced 23fold at 0.1 mM
ceramide
-
-
Cetyltrimethylammonium bromide
-
low concentrations
cholate
-
-
cholesterol
-
sphingomyelinase activity is higher in the cholesterol-induced liquid-ordered phase than in the gel phase
cholesterol
-
sphingomyelinase is enhanced by cholesterol and by lipids with an intrinsic negative curvature, e.g. phosphatidylethanolamine
choline
-
required for enzyme activity, and probably to prevent enzyme dissociation from the membranes
Cutsum
-
-
-
Cutsum
-
-
-
daunorubicin
-
-
deoxycholate
-
3fold stimulation at concentrations above 0.1%
deoxycholate
-
-
Detergents
-
-
Detergents
-
-
Detergents
-
activation
Diacylglycerols
-
-
dioleoyl-phosphatidylserine
Q9NY59
0.05 mM, 4fold activation
dithiothreitol
-
2fold enhanced activity at 3 mM
dithiothreitol
-
activation in a dose dependent manner
dithiothreitol
-
approx. 10fold activation at 3-4 mM
dithiothreitol
Q9ET64
required for full activity
DTT
Q9JJY3
activates in vivo by severalfold
EGTA
-
Cu2+ not inhibitory when EGTA added prior
Fas ligand
-
activates sphingomyelinases, expecially acid SMase
-
galectin-I
-
human, induces apoptosis and initiates the acid SMase-mediated release of ceramide
-
glutathione
Q9JJY3
activates in vivo by severalfold
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
linoleic acid
-
approx. 20% stimulation at 0.8 mM, inhibition above
linolenic acid
-
approx. 30% stimulation at 0.8-1.6 mM, inhibition above
Lipids
-
saturated and unsaturated fatty acids
-
lyso-phosphatidylcholine
-
-
oleic acid
-
approx. 40% stimulation at 0.8 mM, inhibition above
ONOO-
-
peroxynitrite specifically activates the acidic sphingomyelinase
phorbol 12-myristate 13-acetate/protein kinase Cdelta
-
activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation, which is mediated by phorbol 12-myristate 13-acetate, that induces also membrane translocation of ASMase, formation of a novel PKCdelta-ASMase complex after PMA stimulation, mechanism, overview
-
phosphatidic acid
-
-
phosphatidic acid
-
-
phosphatidic acid
-
anionic phospholipids required for activity, maximal activation at 1 mM, 33% of activation with phosphatidylserine
phosphatidylcholine
-
0.2 mM, 2fold activation
phosphatidylcholine-specific phospholipase C
-
increases the N-SMase activity up to 2fold
-
phosphatidylethanol
Q9NY59
0.05 mM, 2fold activation
phosphatidylethanolamine
-
-
phosphatidylethanolamine
-
0.2 mM, 2.9fold activation
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
phosphatidylglycerol
O60906, Q9NY59
activates nSMase2
phosphatidylglycerol
D6MZJ6
enzymatic activity is induced 8fold at 0.1 mM
phosphatidylinositol
-
-
phosphatidylinositol
-
-
phosphatidylinositol
-
anionic phospholipids required for activity, maximal activation at 1 mM, 53% of activation with phosphatidylserine
phosphatidylserine
-
anionic phospholipids required for activity, maximal activation at 1 mM
phosphatidylserine
-
required for activity
phosphatidylserine
-
0.2 mM, approx. 108fold activation of sphingomyelin hydrolysis in the presence of 0.1% Triton X-100
phosphatidylserine
-
0.2 mM, 3.8fold activation
phosphatidylserine
-
0.1-0.15 mM, approx. 40fold activation
phosphatidylserine
-
-
phosphatidylserine
Q9NY59
0.05 mM, 4fold activation
phosphatidylserine
Q9NXE4
enhances activity
phosphatidylserine
O60906, Q9NY59
activates nSMase2
phosphatidylserine
-
-
phosphatidylserine
D6MZJ6
enzymatic activity is induced 15fold at 0.1 mM
phosphatidylserine
-
-
protein kinase C-zeta
-
mediates the activation of N-SMase by 1,25-dihydroxyvitamin D3, while protein kinase C-delta inhibits the activation
-
reduced glutathione
-
activation in a dose dependent manner
Salts
-
trihydroxy- and dihydroxy-bile salt
-
saposin C
-
presence of sphingolipid activator proteins, e. g. saponsins, is not essential for activity. Saposin C increases activity of the P153A mutant enzyme, but does not result in complete restoration of the activity
-
Sodium cholate
A6P7M9
129% relative activity at 6% (v/v) sodium cholate
Sodium deoxycholate
-
-
Sodium deoxycholate
-
-
Sodium deoxycholate
-
-
Sodium deoxycholate
-
4.4fold activation of S-mSMase epsilon at 2 mM, 4.7fold activation of S-mSMase zeta at 1 mM
sphingomyelin
-
dietary sphingomyelin increases the alk-Smase activity in the colon by 65%, the increased activity is associated with increased protein and mRNA expression
staurosporine
-
activates neutral spingomyelinase in a multiphasic manner
stearic acid
-
approx. 20% stimulation at 0.4-0.8 mM, inhibition above
taurochenodeoxycholate
-
strong activation, maximal activation at approx. 2 mM
taurochenodeoxycholate
-
-
taurochenodeoxycholate
-
; stimulates hydrolysis of sphingomyelin and platelet-activating factor
taurocholate
-
-
taurocholate
-
strong activation, maximal activation at approx. 10 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
taurocholate
-
the enzyme activity is specifically stimulated by 6 mM 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
-
TNFalpha
-
activates the enzyme, which is prevented by pentoxifylline
-
Triacylglycerols
-
-
Tripalmitoylglycerol
-
-
Triton X-100
-
stimulates up to 15fold
Triton X-100
-
-
Triton X-100
-
activation at very low concentrations
Triton X-100
-
activation with sphingomyelin
Triton X-100
-
activation of enzyme A and B
Triton X-100
-
0.1%, approx. 108fold activation of sphingomyelin hydrolysis in the presence of 0.2 mM phosphatidylserine; 0.1%, approx. 61fold activation of sphingomyelin hydrolysis in the presence of 0.2 mM phosphatidylserine
Triton X-100
-
required for activity, maximal activation at 0.1%
Triton X-100
-
required for full activity
Triton X-100
-
0.02%, approx. 3fold activation of T-mSMase gamma
Triton X-100
A6P7M9
205% relative activity at 0.1% (v/v) Triton X-100
tumor necrosis factor
-
induces N-SMase activity
-
tumor necrosis factor
-
there is a significant increase in ASMase activity after treatment of MVEC cells with tmor necrosis factor
-
tumor necrosis factor-alpha
-
activates neutral spingomyelinase in a multiphasic manner
-
Tween 20
-
-
monoacylglycerols
-
-
additional information
-
-
-
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
-
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
Q9NXE4
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
-
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
O60906, Q9NY59
nSMase1 activity required reducing agents; nSMase2 is activated by anionic phospholipids
-
additional information
-
nSMase2 is induced by TNFalpha, cytokines, cellular stresses such as UV-light, heat shock, apoptosis, and chemotherapeutic drugs, and by pathological stimuli such as amyloid-beta peptides and lipopolysaccharides
-
additional information
-
secretory sphingomyelinase is upregulated in chronic heart failure
-
additional information
-
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
-
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
-
1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine induces neutral sphingomyelinase activity
-
additional information
-
age-related increase in the activity of NSMase-2, attenuated by calorie restriction, aging and interleukin-1beta stimulate NSMase-2 by different mechanisms, overview
-
additional information
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
-
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
D6MZJ6
phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol have minimal effects on MA-nSMase activity
-
additional information
A6P7M9
not affected by 6% sodium taurocholate and 6% sodium deoxycholate
-
additional information
-
no effect on activity by monosialic ganglioside GM3 and phospholipids
-
additional information
Q9JJY3
the enzyme requires a hydrophobic environment for activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.048
1-alkyl-lyso-platelet activating factor
-
37C, pH 7.4
1.7
2-(N-hexadecanoylamino)-4-nitrophenylphosphorylcholine
-
37C, pH 5.5
0.034
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine
-
in presence of Mg2+
0.34
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine
-
-
0.027
2n-hexadecanoylamino-4-nitrophenylphosphorylcholine
-
-
14.5
bis-p-nitrophenyl phosphate
-
-
11.6
p-nitrophenylphosporylcholine
-
-
0.00059
sphingomyelin
-
-
0.0039
sphingomyelin
-
37C, pH 7.4
0.01871
sphingomyelin
Q9NXE4
-
0.0203
sphingomyelin
-
in 100 mM Tris-HCl (pH 7.5), at 37C
0.024
sphingomyelin
-
-
0.025
sphingomyelin
-
-
0.027
sphingomyelin
-
37C, pH 7.4, recombinant nSMase2 in yeast microsomes
0.032
sphingomyelin
-
-
0.032
sphingomyelin
-
37C, pH 4.8
0.038
sphingomyelin
-
in presence of Mg2+ and Triton X-100
0.04
sphingomyelin
-
37C, pH 7.4
0.055
sphingomyelin
-
-
0.069
sphingomyelin
-
-
0.079
sphingomyelin
-
-
0.095
sphingomyelin
-
enzyme B
0.1
sphingomyelin
-
-
0.1
sphingomyelin
-
37C, pH 7.5
0.13
sphingomyelin
-
-
0.17
sphingomyelin
-
in presence of Mg2+ and sodium deoxycholate
0.18
sphingomyelin
-
-
0.2
sphingomyelin
-
-
0.3
sphingomyelin
-
enzyme A
0.35
sphingomyelin
-
37C, pH 7.5
0.405
sphingomyelin
-
in presence of Triton X-100
0.5 - 0.9
sphingomyelin
-
-
0.526
sphingomyelin
-
-
0.565
sphingomyelin
-
in presence of sodium deoxycholate
0.62
sphingomyelin
-
microsomes
1.2
sphingomyelin
-
lysosomes, at 0.5 mM sphingomyelin
1.25
sphingomyelin
-
37C, pH 9.0
13
sphingomyelin
-
lysosomes, at 2 mM sphingomyelin
60 - 90
sphingomyelin
-
-
0.174
hexadecanoyl-p-nitrophenyl phosphorylcholine
-
-
additional information
additional information
-
different SMase kinetic steps are differentially regulated by non-substrate lipids, overview
-
additional information
additional information
-
Michaelis-Menten kinetics
-
0.0136
Platelet-activating factor
-
-
additional information
sphingomyelin
-
comparison of values from enzymes of normal and mutated tissues; influence of detergents
additional information
sphingomyelin
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.9
2-hexadecanoylamino-4-nitrophenylphosphocholine
-
37C, pH 7.5
13
lysophosphatidylcholine
-
37C, pH 7.5
3.6
sphingomyelin
-
37C, pH 7.5
210
sphingomyelin
-
37C, pH 7.5
400
sphingomyelin
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5
Chloroquine
-
diphosphate salt
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
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
1,3,5-tri-O-dodecylsulfonyl-D_myo-inositol
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.1
1,3,5-tri-O-ethylsulfonyl-D-myo-inositol
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.1
1,3,5-tri-O-methylsulfonyl-D-myo-inositol
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.1
1,3,5-tri-O-octylsulfonyl-D-myo-inositol
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.0009
1-O-dodecylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.1
1-O-ethylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.043
1-O-hexylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.1
1-O-methylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.004
1-O-octylsulfonyl-D-myo-inositol 3,5-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.5
3',5'-cAMP
-
IC50: above 0.5 mM
0.05
3-acetyl-11-keto-beta-boswellic acid
-
acid SMase
0.5
5-adenoylimino phosphate
-
IC50: above 0.5 mM
0.00044
6-O-dodecylsulfonyl-D-glucose 2,4-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.0396
6-O-ethylsulfonyl-D-glucose 2,4-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.00416
6-O-hexylsulfonyl-D-glucose 2,4-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.00234
6-O-octylsulfonyl-D-glucose 2,4-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.07
AD2765
-
pH and temperature not specified in the publication
0.5
adeno 5'-diphosphate
-
IC50: above 0.5 mM
0.2
adeno-2',3'-cyclic phospho 5'-monophosphate
-
IC50: 0.2 mM
0.5
adeno-2',3'-cyclic phospho 5'-phosphosulfate
-
IC50: 0.5 mM
0.3
ADP
-
IC50: 0.3 mM
0.014
alpha-mangostin
-
pH and temperature not specified in the publication
0.08
AMP
-
IC50: 0.08 mM, non-competitive inhibition
0.8
ATP
-
IC50: 0.8 mM
0.1
cis, cis-cyclohexane 1,3,5-trisphosphate
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.0192
cowanin
-
pH and temperature not specified in the publication
0.0109
cowanol
-
pH and temperature not specified in the publication
0.04
lysophosphatidic acid
-
IC50: 0.04 mM
0.0267
myo-inositol 1,3,5-trisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.1
myo-Inositol 3,5-bisphosphate
-
IC50 above 0.1 mM, in 100 mM NaOAc, pH 5.2, at 37C
0.0012
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
0.5
NAD+
-
IC50: above 0.5 mM
0.5
NADP+
-
IC50: above 0.5 mM
10
phosphate
-
IC50: 10 mM, non-competitive inhibition
0.00093
phosphatidyl inositol 3,5-bisphosphate
-
in 100 mM NaOAc, pH 5.2, at 37C
0.003
phosphatidyl-myo-inositol 3,4,5-triphosphate
-
IC50: 0.003 mM
0.25
phosphatidyl-myo-inositol 4,5-diphosphate
-
IC50: 0.25 mM
2
phosphatidylcholine
-
IC50: 2 mM
2
Zn2+
-
in 100 mM Tris-HCl buffer (pH 7.5), at 37C
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 37C
0.00000045
Q4LEU0
recombinant enzyme, using sphingomyelin as substrate
0.000025
-
chromatin
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 37C
0.0000427
Q4LEU0
wild type enzyme after heat shock for 1 h at 37C, 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 37C
0.0000542
Q4LEU0
wild type enzyme after heat shock for 1 h at 38C, 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 37C
0.000114
-
after 1fold purification, at 37C
0.0009
-
nuclear membrane
0.007
Q6UWV6
alkaline sphingomyelinase in liver with steatosis
0.021
-
S-mSMase zeta
0.024
-
S-mSMase epsilon
0.027
-
recombinant human Alk-SMase, in 50 mM Tris
0.033
-
T-mSMase gamma
0.047
Q6UWV6
alkaline sphingomyelinase in liver with sclerosing cholangitis
0.051
-
T-mSMase delta
0.052
-
phospholipid pre-incubated nuclear membrane
0.063
-
T-mSMase alpha
0.11
-
T-mSMase beta
0.23
-
-
0.246
A6P7M9
culture supernatant, in 50 mM glycine-NaOH buffer (pH 9.6), at 37C
0.46
-
sphingosylphosphocholine hydrolysis
0.49
-
sphingomyelin hydrolysis
0.9334
-
after 8183.3fold purification, at 37C
6.23
-
purified enzyme with substrate platelet-inactivating factor
7.33
-
-
13.3
-
recombinant haSMase
21.1
-
-
33
-
recombinant SMase C
92.8
-
5fold higher specific activity of rhASM purified from CHO cell-harvests stored at -20C
98.4
A6P7M9
400fold purified enzyme, in 50 mM glycine-NaOH buffer (pH 9.0), at 55C
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.; normal and Niemann Pick disease type C fibroblasts
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.; microsomes, lysosomes and plasma membrane
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
different assay conditions, substrates etc.
additional information
-
-
additional information
-
-
additional information
Q9BDR3
quantitative expression analysis in articular chondrocytes; quantitative expression analysis in articular chondrocytes
additional information
-
activity of wild-type and mutant enzymes, overview
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.4 - 4.8
-
in lysosomes
4.5 - 5
-
-
4.5
-
acidic SMase
4.5
-
acidic SMase assay at
4.6 - 4.7
-
-
4.8 - 5
-
bis-4-methylumbelliferyl phosphate and bis-p-nitrophenyl phosphate
5 - 5.5
-
hexadecanoyl-p-nitrophenyl phosphorylcholine
5 - 5.5
-
depending on buffer
5
-
acidic sphingomyelinase
5
-
enzyme A and B
5
-
acidic sphingomyelinase
5
-
assay at
5
-
ASM assay at
5
-
assay at, acid SMase
5
-
assay at
5
-
assay at
5
-
acid SMase assay at
5
-
assay at
5.2
-
in sodium acetate buffer
5.5 - 7.5
Q8IUN0
assay at
5.5
-
-
5.5
-
T-mSMase isoform alpha
5.5
-
assay at
6 - 7.8
D3TNH1, I2CMF9, I2CMG0, I2CMG1
assay at; assay at; assay at; assay at
6.5
-
-
7 - 7.2
-
plasma membranes
7 - 8
-
-
7
-
neutral sphingomyelinase
7
-
neutral sphingomyelinase
7
-
T-mSMase isoforms beta and gamma, S-mSMase zeta
7
Q9NXE4
-
7
-
neutral SMase assay at
7.2
-
microsomes
7.2
-
hemolysis assay at
7.4
P09599
N-SMase
7.4
-
N-SMase
7.4
O60906, Q9NY59
N-SMase; N-SMase
7.4
Q9RLV9
N-SMase
7.4
-
nSMase2
7.4
-
neutral SMase
7.4
-
assay at
7.4
-
assay at
7.4
-
membrane binding assay at
7.4
Q9JJY3
assay at
7.5 - 8
-
S-mSMase isoform epsilon
7.5
-
T-mSMase isoforms alpha and delta
7.5
-
alk-SMase activity with platelet-inactivating factor
7.5
-
alk-SMase activity with platelet-inactivating factor; hydrolysis of platelet-activating factor
7.5
-
assay at, neutral SMase
7.5
-
assay at
7.5
Q4LEU0
recombinant neutral SMase 1 hydrolyzes choline-methyl-sphingomyelin optimally at pH 7.5 in the presence of an Mg2+ ion
7.5
D6MZJ6
the MA-nSMase has no acid SMase activity
7.5
-
assay at
7.6
-
assay at, nuclear membranes
8
-
S-mSMase isoform zeta
8
I4DXK5
assay at
8.4
-
assay at, chromatin
9
Q6UWV6
recombinant alk-SMase
9
-
alk-SMase activity on sphingomyelin
9
-
alk-SMase activity on sphingomyelin; hydrolysis of sphingomyelin
9
-
assay at, alkaline SMase
9
-
alkaline sphingomyelinase assay at
9
-
alkaline SMase assay at
additional information
D3TNH1, I2CMF9, I2CMG0, I2CMG1
the enzyme is activated by the low gut pH; the enzyme is activated by the low gut pH; the enzyme is activated by the low gut pH; the enzyme is activated by the low gut pH
additional information
-
acidic pH optimum
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 10
-
activity range
3.5 - 6.5
-
natural substrate
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
Q9NY59
approx. 5% of maximal activity at pH 4.5, approx. 15% of maximal activity at pH 9.0
5 - 7.5
-
lysosomal enzyme stimulated by different divalent cations
5 - 8
-
-
5 - 8.5
-
plasma membranes
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 - 8.5
-
approx. 10% of maximal activity at pH 6.0 and pH 8.5, respectively
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
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
additional information
-
neutral pH required for activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
membrane binding assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
in vivo assay at
37
-
assay at
37
-
hemolysis assay at
37
-
assay at
37
-
assay at
37
Q9JJY3
assay at
37
-
assay at
37
Q8IUN0
assay at
37
I4DXK5
assay at
37
P17405
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
-
up to
60
-
up to
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.3
-
isoelectric focusing
6.33
-
deduced from nucleotide sequence
7.15
-
isoelectric focusing
8.6
D6MZJ6
calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
epithelial cell
Manually annotated by BRENDA team
Entamoeba histolytica HM1
-
-
-
Manually annotated by BRENDA team
-
murine macrophage cell line
Manually annotated by BRENDA team
-
cortical astrocyte, acid SMase
Manually annotated by BRENDA team
-
umbilical cord blood. Zn2+-dependent sphingomyelinase acid activity is much higher than Zn2+ independent isoform activity in both fetal and mother's blood
Manually annotated by BRENDA team
-
a secreted, zinc-activated form of ASM is found in the plasma which plays an important role in the development of atherosclerosis
Manually annotated by BRENDA team
-
distribution in tissues, brain most active source
Manually annotated by BRENDA team
-
central nervous system myelin
Manually annotated by BRENDA team
-
grey matter, high nSMase2 activity
Manually annotated by BRENDA team
-
isozymes nSMase2 and nSMase3
Manually annotated by BRENDA team
O60906, Q9NY59
nSMase1, specific for
Manually annotated by BRENDA team
-
brain-specific N-SMase2
Manually annotated by BRENDA team
E9LUE7, E9LUE8, E9LUE9, P17405
splicing form ASM-4
Manually annotated by BRENDA team
-
no mutation identified
Manually annotated by BRENDA team
-
in hippocampus the enzyme activity is significantly higher than in striatum and cortex. Significant increase in cortical membrane-associated N-Sase activity with age
Manually annotated by BRENDA team
Rattus norvegicus Fischer 344
-
in hippocampus the enzyme activity is significantly higher than in striatum and cortex. Significant increase in cortical membrane-associated N-Sase activity with age
-
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma
Manually annotated by BRENDA team
-
mutation of the enzyme found in
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Rattus norvegicus Fischer 344
-
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
-
Manually annotated by BRENDA team
Q6UWV6
high mRNA levels
Manually annotated by BRENDA team
-
coronary arterial endothelial cells
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
unchanged A-SMase activity in the outer epidermis of chronologically aged skin, in the lower epidermis the activity is reduced
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
bronchial epithelial cell line
Manually annotated by BRENDA team
-
coronary arterial endothelial cells
Manually annotated by BRENDA team
-
isozyme nSMase3
Manually annotated by BRENDA team
-
neutral sphingomyelinase
Manually annotated by BRENDA team
Q6UWV6
expression analysis of alkaline sphingomyelinase forms, overview
Manually annotated by BRENDA team
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
primary
-
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
Rattus norvegicus Fischer 344
-
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
-
Manually annotated by BRENDA team
-
immortalized hippocampal neuron
Manually annotated by BRENDA team
-
human oligodendroglioma cell
Manually annotated by BRENDA team
-
human oligodendroglioma cell line
Manually annotated by BRENDA team
-
deletion of exon 4 in alk-SMase cDNA
Manually annotated by BRENDA team
-
a Jurkat cell line derivative lacking caspase 8
Manually annotated by BRENDA team
Q6UWV6
low mRNA levels
Manually annotated by BRENDA team
-
gastrointestinal tract
Manually annotated by BRENDA team
-
exclusively expressed in intestine, lack of bSMase may be related to colon carcinogenesis
Manually annotated by BRENDA team
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma
Manually annotated by BRENDA team
Q6UWV6
high mRNA levels
Manually annotated by BRENDA team
-
different variants
Manually annotated by BRENDA team
-
predominant tissue
Manually annotated by BRENDA team
-
cell line
Manually annotated by BRENDA team
-
distribution in tissues, liver most active source
Manually annotated by BRENDA team
Q6UWV6
high mRNA levels
Manually annotated by BRENDA team
Q6UWV6
wild-type and mutant alkaline sphingomyelinase forms
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
acid-SMase activity is comparable in lung and intestine, alk-ASMase activity is lower in lung than in intestine
Manually annotated by BRENDA team
-
isolated from bone marrow or peritoneal lavage of gene-targeted mice lacking Asm and their wild-type littermates
Manually annotated by BRENDA team
-
mammary carcinoma cell line
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
first faeces of an infant
Manually annotated by BRENDA team
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
Manually annotated by BRENDA team
E9LUE7, E9LUE8, E9LUE9, P17405
-
Manually annotated by BRENDA team
-
acidic SMase
Manually annotated by BRENDA team
-
fetal, newborn
Manually annotated by BRENDA team
-
from cord blood of infants of 30-40 weeks, of adults from normal healthy volunteers of either sex, from patients with Padgetis disease
Manually annotated by BRENDA team
-
isozyme nSMase3
Manually annotated by BRENDA team
-
acid-SMase activity is comparable in lung and intestine
Manually annotated by BRENDA team
-
high content of S-SMase, secretion
Manually annotated by BRENDA team
additional information
-
-
Manually annotated by BRENDA team
additional information
-
expression of the enzyme in different human tissues
Manually annotated by BRENDA team
additional information
-
maximum activity in the distal jejunum, little activity in bile, liver, pancreas after trypsin treatment
Manually annotated by BRENDA team
additional information
-
age-related increase in the activity of NSMase-2
Manually annotated by BRENDA team
additional information
-
Alk-SMase developmental enzyme activity, overview, Alk-SMase activity decreases with age
Manually annotated by BRENDA team
additional information
-
no detectable activity of acid-SMase in colonic mucosa
Manually annotated by BRENDA team
additional information
-
immunolocalization study of Mg2+-dependent neutral sphingomyelinase, overview
Manually annotated by BRENDA team
additional information
-
ubiquitous tissue distribution of enzyme, distribution of splicing forms, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
neutral sphingomyelinase is concentrated at the endothelial cell surface in caveolae
Manually annotated by BRENDA team
-
neutral sphingomyelinase is concentrated at the endothelial cell surface in caveolae
Manually annotated by BRENDA team
-
age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
Manually annotated by BRENDA team
Rattus norvegicus Fischer 344
-
age-related decreases in the hippocampal and striatal cytosolic N-Sase activities are accompanied by increases in the membrane N-Sase activities
-
Manually annotated by BRENDA team
-
recombinant overexpressed nSMase1
Manually annotated by BRENDA team
Q4LEU0
in the case of HEK293 transfectants, the zebrafish SMase 1 is also colocalized in both the Golgi apparatus and the endoplasmic reticulum
Manually annotated by BRENDA team
-
localizes to the lumen of endosomes
Manually annotated by BRENDA team
-
in presence of NH4Cl
-
Manually annotated by BRENDA team
-
extraction maximized with cutsum
-
Manually annotated by BRENDA team
-
extracellular soluble toxin that induces hemolysis by acting on sphingomyelin-rich erythrocytes of mammals such as ruminants
-
Manually annotated by BRENDA team
-
the enzyme is secreted
-
Manually annotated by BRENDA team
I4DXK5
the enzyme is secreted
-
Manually annotated by BRENDA team
-
the enzyme is secreted
-
Manually annotated by BRENDA team
-
ASM is a secretory protein
-
Manually annotated by BRENDA team
-
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
Manually annotated by BRENDA team
Q9RLV9
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
Manually annotated by BRENDA team
P09599
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
Manually annotated by BRENDA team
-
secreted enzyme, infection of macrophages with Salmonella enterica serovar typhimurium stimulates extracellular ASM secretion
-
Manually annotated by BRENDA team
-
secretory sphingomyelinase S-SMase is secreted by endothelial cells upon stimulation with lipopolysaccharides and pro-inflammatory cytokines such as TNF-alpha
-
Manually annotated by BRENDA team
-
secreted aSMase, S-SMase
-
Manually annotated by BRENDA team
-
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
-
Manually annotated by BRENDA team
Bacillus cereus IAM1029
-
-
-
-
Manually annotated by BRENDA team
Listeria ivanovii nSMase
-
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
-
Manually annotated by BRENDA team
-
the enzyme is secreted
-
-
Manually annotated by BRENDA team
Bacillus cereus nSMase
-
nSMase, with a cleavable secretory signal sequence at their N-terminus, is a secretory protein released from cells
-
-
Manually annotated by BRENDA team
Q4LEU0
SMase 1 is also localized in the Golgi apparatus
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
inner lysosomal membrane, detachment caused by weak bases inhibits the enzyme
Manually annotated by BRENDA team
-
translocation of ASMase from endolysosomes to the plasma membrane after sustained phorbol 12-myristate 13-acetate treatment
Manually annotated by BRENDA team
-
can rapidly move from lysosomes to cell surface upon stimulation by cytokines and other factors
Manually annotated by BRENDA team
-
ASM is a secretory protein
Manually annotated by BRENDA team
-
localizes to the lumen of lysosomes
Manually annotated by BRENDA team
-
lysosomal aSMase, L-SMase
Manually annotated by BRENDA team
-
lysosomal phosphodiesterase acid SMase
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
catalytic region of nSMase2 localizes to the cytosolic side of the plasma membrane, proposed membrane topology model, overview
Manually annotated by BRENDA team
-
intestinal microvillar membrane
Manually annotated by BRENDA team
O60906, Q9NY59
nSMase1 contains two putative transmembrane domains at the C-terminus
Manually annotated by BRENDA team
-
nSMase2 is predominantly membrane-bound
Manually annotated by BRENDA team
-
phosphorylation of a specific serine residue on ASM (S508) by protein kinase C-delta is required for its translocation to the cell surface
Manually annotated by BRENDA team
Entamoeba histolytica HM1
-
associated
-
Manually annotated by BRENDA team
Plasmodium falciparum Honduras 1
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Fischer 344
-
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
-
Manually annotated by BRENDA team
Q4LEU0
in zebrafish embryonic cells, the endogenous SMase enzyme is localized in the microsomal fraction
-
Manually annotated by BRENDA team