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Enzyme Nomenclature
Information on EC 3.1.4.12 - sphingomyelin phosphodiesterase
for references in articles please use BRENDA:EC3.1.4.12
Word Map on EC 3.1.4.12
- 3.1.4.12
- aureus
-
sphingolipids
- lysosomal
- niemann-pick
- cholesterol
-
staphylococcal
- phospholipid
- clostridium
-
permeabilized
- sphingosine
- endothelial
- perfringens
- phosphatidylcholine
- erythrocyte
-
raft
- ceramidase
-
hemolytic
- c2-ceramide
- venom
-
bilayer
-
tnf-alpha
-
cell-permeable
-
pore-forming
- scorpion
- phosphatidylserine
-
microdomains
- fumonisin
-
enterotoxin
- sphingosine-1-phosphate
-
ceramide-induced
- desipramine
-
hepatosplenomegaly
- gangrene
- phosphorylcholine
- glucosylceramide
- lecithinase
- pc-plc
-
dermonecrotic
- filipin
- gaucher
-
streptolysin
- glucocerebrosidase
-
phosphatidylcholine-specific
- amitriptyline
-
cytolysin
- medicine
-
myonecrosis
- drug development
-
exoproteins
-
nonhemolytic
-
coagulase
-
transbilayer
- pharmacology
- diagnostics
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
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EC NUMBER 
COMMENTARY 
3.1.4.12
-
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RECOMMENDED NAME
GeneOntology No.
sphingomyelin phosphodiesterase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a sphingomyelin + H2O = a ceramide + phosphocholine
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-
-
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a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases; catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, histidine residues, His136 and His272, are essential for catalysis
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, structure-function analysis, overview
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, e.g. Glu53, Asp126, Asp295, and His296 are essential, structure-function analysis, overview
-
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, overview
-
-
a sphingomyelin + H2O = a ceramide + phosphocholine
catalytic mechanism, a number of key residues involved in metal binding and catalysis are conserved in neutral sphingomyelinases, structure-function analysis, overview
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
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-
-
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additional information
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SMase belongs to the family of interfacial enzymes that carry out processive catalytic turnover at the interface, SMase binds rapidly and avidly to sphingomyelin vesicles and it is fully active as a monomer at the interface
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
sphingomyelin cholinephosphohydrolase
Has very little activity on phosphatidylcholine.
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CAS REGISTRY NUMBER
COMMENTARY
9031-54-3
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
serovar Lai, gene sph2 or LA_1029 encoding isozyme Sph2
UniProt
serovar Lai, gene sph2 or LA_1029 encoding isozyme Sph2
UniProt
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135157, 135166, 650366, 650502, 650584, 651338, 651801, 652701, 663762, 664187, 664590, 664837, 679082, 681266, 681689, 693938, 704040, 714410, 729131, 729132
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135146, 135147, 135148, 135149, 135150, 135152, 135153, 135154, 135156, 135159, 135160, 135161, 135164, 135168, 135169, 135176, 135178, 135179, 135180, 135184, 135185, 135187, 651338, 652079, 653119, 663809, 663951, 663974, 664216, 664262, 664495, 664500, 664532, 664929, 665122, 665138, 665626, 665828, 666111, 666134, 666964, 677601, 677818, 677875, 678939, 679144, 679649, 679682, 679685, 680745, 680767, 681259, 681266, 681322, 681494, 682246, 682477, 682983, 691060, 691456, 692009, 692236, 692274, 694111, 694201, 694260, 694284, 705457, 705473, 714689, 715614, 715641, 716445, 729101, 730294, 730356
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haSMase deficiency due to mutations in haSMase gene leads to Niemann-Pick disease, an autosomal recessive sphingolipidosis
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one form of Niemann-Pick disease is caused by a deficiency of acid sphingomyelinase
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135154, 135162, 135188, 652079, 664859, 665814, 666142, 679649, 680063, 690455, 691696, 692073, 693467, 693810, 694904, 701641, 714052, 714940, 715616, 729609
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the enzyme is a member of the metallophosphoesterase enzyme family
evolution
the enzyme from Streptomyces seems to be a typical bacterial SMase with a primary structure unusual for known bacterial SMases, primary structure comparisons and phylogenetic analysis
evolution
the enzyme belongs to the DNase I superfamily, which contains the exo-endo-phosphatase domain, the domain lacks only in isozyme Sph4, all isozymes lack the beta-hairpin loop, the organism encodes genes Sph1, Sph2, Sph3, Sph4 and SphH, structure comparisons, overview
evolution
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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
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evolution
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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
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malfunction
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acid SMase-deficient mice show reduced pulmonary ceramide levels and attenuated leukocyte influx into the alveolar space
malfunction
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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
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treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
malfunction
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loss of nSMase activity leads to a Big-Eye-like phenotype, and affect s protein trafficking, as well as VSG trafficking, overview
malfunction
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deficiency of the enzyme leads to lysosomal accumulation of sphingomyelin resulting in in Niemann-Pick types A and B diseases
malfunction
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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
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
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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; 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; 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; 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
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treatment with high-dose glucose increases glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM-/- cells
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metabolism
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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
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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
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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
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the essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei
metabolism
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interaction in the NO/NOS and SMases/ceramide signaling pathways, overview
metabolism
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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
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metabolism
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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
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physiological function
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in HepG2 cells SMase treatment significantly enhances the esterification of cholesterol by a 50% with respect to control cells
physiological function
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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
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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
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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
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acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
physiological function
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acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
physiological function
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all-trans-retinoic acid regulation of nSMase2, overview
physiological function
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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
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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
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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
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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
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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
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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
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the enzyme is a virulence factor for septicemia. Ganglioside GM3 is the primary cellular receptor for the enzyme, and the beta-hairpin region is the tethering region for gangliosides
physiological function
neutral sphingomyelinase-2 is the major sphingomyelinase activated in response to proinflammatory cytokines and during oxidative stress. The enzyme may be a novel substrate for thioredoxin
physiological function
critical role(s) of sphingomyelinase and ceramidase during pregnancy and lactation and their downstream effects on adult progeny fitness. The mother provides her offspring with nutrients required for development solely via intrauterine lactation; 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; 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; 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
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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 recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
physiological function
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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
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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
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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
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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
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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
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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
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physiological function
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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
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physiological function
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the recombinant isozyme Sph2 performs the Mg2+ -dependent hemolysis of erythrocytes
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physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
-
physiological function
-
acid sphingomyelinase regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate. ASM increases glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3beta. In addition, ASM induces up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase phosphorylation. ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver
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additional information
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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
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besides the aSMase, an alkaline sphingomyelinase and two neutral sphingomyelinases 1 and 2, nSMase1 and nSMase2, exist
additional information
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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
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comparison of in vivo activity of nSMase in Schistosoma mansoni with the activity in Schistosoma haematobium, overview
additional information
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comparison of in vivo activity of nSMase in Schistosoma mansoni with the activity in Schistosoma haematobium, overview
additional information
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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
homology model of aSMase enzyme with consensus motif NX3CX3N, where X is any amino acid, overview. The central cysteine (C385) of the motif is also involved in a disulfide bridge with C431. The enzyme aSMase contains a sphingolipid activator protein (saposin) domain in its N-terminal region followed by a proline-rich linker, this domain also plays a role in stabilizing the structure of the enzyme
additional information
isozyme Sph2 structure homology modeling, the isozyme Sph2 is unique and possesses the Mg2+-binding Glu53 residue in the metal-binding site and two His residues, His151 and His286, in the catalytic site
additional information
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establishing enzyme activity in lipid vesicles, method development, overview. Both lipase activities are sensitive to vesicle size, but in opposite ways: while phospholipase C is higher with larger vesicles, sphingomyelinase activity is lower
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additional information
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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
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1,2-dioleoyl-sn-glycero-3-phosphocholine + H2O
?
0.7% activity compared to sphingomyelin
-
-
?
1-alkyl-lyso-platelet activating factor + H2O
1-alkylglycerol + choline phosphate
-
-
-
?
1-O-octadecyl-2-lyso-platelet-activating factor + H2O
1-O-octadecyl-sn-glycerol + phosphocholine
very little activity
-
-
?
2-(N-hexadecanoylamino)-4-nitrophenylphosphorylcholine + H2O
2-(N-hexadecanoylamino)-4-nitrophenol + choline phosphate
-
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
4-nitrobenz-2-oxa-1,3-diazole-sphingosylphosphorylcholine + H2O
4-nitrobenz-2-oxa-1,3-diazole-sphingosine + choline phosphate
-
-
-
?
6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-hexanoyl)sphingosyl phosphocholine + H2O
6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-N-hexanoylsphingosine + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphocholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
L-alpha-phosphatidylinositol + H2O
?
5.63% activity compared to sphingomyelin
-
-
?
lissamine-rhodamine dodecanoyl sphingosyl phosphocholine + H2O
?
-
neutral sphingomyelinase
-
-
?
lyso-platelet-activating factor + H2O
1-alkylglycerol + choline phosphate
-
103fold higher activity than with sphingomyelin in the absence of detergent
-
?
lyso-platelet-activating factor + H2O
alkylglycerol + choline phosphate
-
55% of activity with sphingomyelin in the absence of detergent
-
?
N-dodecanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-dodecanoylsphingosine + choline phosphate
-
-
-
?
N-hexanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + H2O
4-nitrobenz-2-oxa-1,3-diazole-N-hexanoylsphingosine + choline phosphate
-
-
-
?
N-methyl-sphingomyelin + H2O
N-methyl-N-acylsphingosine + choline phosphate
-
-
-
-
?
p-nitrophenylphosphorylcholine + H2O
choline phosphate + p-nitrophenol
-
-
-
-
?
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
-
low activity
-
?
phosphatidylethanolamine + H2O
diacylglycerol + phosphorylethanolamine
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
sphingosylphosphorylcholine + H2O
sphingosine + choline phosphate
-
25% of activity with sphingomyelin
-
?
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
2.11% activity compared to sphingomyelin
-
-
?
1,2-di [(cis)-9-octadecenoyl]-sn-glycero-3-phospho-(1-rac-glycerol) + H2O
?
Streptomyces griseocarneus NBRC13471
2.11% activity compared to sphingomyelin
-
-
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
9.04% activity compared to sphingomyelin
-
-
?
1,2-di(cis-9-octadecenoyl)-sn-glycerol-3-phosphate + H2O
?
Streptomyces griseocarneus NBRC13471
9.04% activity compared to sphingomyelin
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
4.93% activity compared to sphingomyelin
-
-
?
1,2-dioleoyl-sn-glycero-3-phospho-L-serine + H2O
?
Streptomyces griseocarneus NBRC13471
4.93% activity compared to sphingomyelin
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
?
2-hexadecanoylamino-4-nitrophenylphosphocholine + H2O
2-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
2-n-hexadecanoylamino-4-nitrophenylphosphorylcholine + H2O
2-n-hexadecanoylamino-4-nitrophenol + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine + H2O
6-hexadecanoylamino-4-methylumbelliferone + choline phosphate
-
-
-
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine, ceramide colocalizes with acetylated tubulin in primary cilia and the mitotic spindle of human embryonic stem cells
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
i.e. an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
6-N-(7-nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
using radiolabelled C12-sphingomyelin as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
using the fluorescent substrate BODIPY-FL-C12-SM, i.e. N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, D-7711
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
6-N-(7-N´nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
using the fluorescent substrate BODIPY-FL-C12-SM, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, or D-7711
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
a ceramide is an N-acylsphingosine
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
hexadecanoyl-p-nitrophenylphosphorylcholine + H2O
hexadecanoyl-p-nitrophenol + choline phosphate
-
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
-
-
?
lysophosphatidylcholine + H2O
1-acylglycerol + choline phosphate
-
-
-
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
-
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
198fold higher activity than with sphingomyelin in the absence of detergent
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
580% of activity with sphingomyelin in the absence of detergent
-
?
lysophosphatidylcholine + H2O
acylglycerol + choline phosphate
-
8% of activity with sphingomyelin
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
in the presence of 0.08% sodium taurodeoxycholate
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
-
-
-
?
phosphatidylcholine + H2O
diacylglycerol + choline phosphate
-
8% of activity with sphingomyelin
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
-
in the presence of 0.08% sodium taurodeoxycholate
-
?
phosphatidylglycerol + H2O
diacylglycerol + glycerolphosphate
-
in the absence of detergents an in the presence of 0.05% Nonidet P-40
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
-
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
-
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
sphingomyelin + H2O
?
-
-
135146, 135147, 135148, 135149, 135150, 135153, 135156, 135159, 135160, 135161, 135168, 135169, 135187
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
cholesterol activation of sphingomyelinase and the strong affinity of cholesterol for sphingomyelin allows the rapid, localized and self-contained production of the metabolic signal ceramide in specific microdomains
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
hydrolysis of sphingomyelin dispersed in diheptanoylphosphatidyl-choline. Premicellar complexes of sphingomyelinase mediate enzyme exchange for the stationary phase turnover
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
changes in the initial composition and topography of mixed monolayers of sphingomyelin and ceramide modulate the sphingomyelin degradation by the enzyme, overview, the enzyme in an extracellular toxin that exhibits potent hemolytic activity against sphingomyelin-rich erythrocytes in mammals
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
SMase shows very low activity against condensed sphingomyelin, but is active on loosely organized sphingomyelin in bilayers and monolayers, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid sphingomyelinase is involved in ceramide signaling, which is important in the lipid raft clustering and formation of redox signaling platform in cell membranes, overview, reactive oxygen species derived from ASM/ceramide triggered lipid raft redox signaling platforms can feedback regulate the ASM activity, FasL-induced O2- may be involved in this regulatory mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
the enzyme is important in the ceramide catabolism, overview
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
677818, 677875, 678250, 678375, 678939, 679144, 679604, 679649, 679682, 679685, 680745, 680754, 680767, 681259, 681266, 681322, 682246, 682477, 682983, 691060, 691456, 692009, 692236, 692274, 694111, 694201, 694260, 694284, 705457, 705473
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
very low activity in the absence of detergent
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma. Mutations of the enzyme found in colon cancer cells. IN the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the sap-like domain of human acid sphingomyelinase has activator-like functions, as well as importance as an integral part of acid spingomyelinase required for normal enzyme activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid SMase is involved in colonic cancer development and apoptosis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview, dietary SM inhibits colonic carcinogenesis by a mechanism related to SM digestion in the gut, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
degradation of sphingomyelin
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
exogenous sphingomyelinase causes impaired intestinal epithelial barrier function, Caco-2 cell monolayers are used as in vitro model for the intestinal barrier, exogenous sphingomyelinase increases transepithelial permeability and decreases transepithelial resistance at concentrations as low as 0.01 U/ml, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview, signaling roles of nSMase2 implicated in apoptosis, inflammation, cell growth, and differentiation, and Alzheimer disease, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
secretory sphingomyelinase is upregulated in chronic heart failure, S-SMase further correlates with reduced skeletal quadriceps muscle strength as well as impaired peripheral vasodilator capacity, physiological function and parameters of S-SMase in heart tissue, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
nSMase2 uses sphingomyelin preferentially as a substrate in vitro with no activity against lyso-PAF
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
A-SMase in the outer epidermis is essential for basal permeability function, A-SMase activity in the lower epidermis is involved in basal permeability barrier homeostasis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is important in ceramide metabolism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
SMase C causes hemolysis and thus is suspected to be a potential virulence factor
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
D-erythrosphingosine or dihydroxysphingosine configuration of sphingomyelin results in a 3-5fold faster hydrolysis in comparison to a D-threo or L-erythro configuration
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
erythro-isomers of DL-trans-2-N-palmitoyl-1-O-phosphorylcholinesphingosine or dihydrosphingosine hydrolyzed faster than the threo-isomer
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
age-related increase in the activity of NSMase-2 is responsible for the interleukin-1beta hyperresponsiveness and a decrease in GSH levels, phenotype, regulation of neutral sphingomyelinase-2 by GSH in oxidative stress in aging-associated inflammation, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, and hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
DL-erythro-N-palmitoylsphingophosphorylcholine, N-stearylsphingophosphorylcholine, N-lignocerylsphingophosphorylcholine in monomolecular layers
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
100% activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Streptomyces griseocarneus NBRC13471
100% activity
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
-
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
127fold higher activity than with sphingomyelin in the absence of detergent
-
?
sphingosylphosphocholine + H2O
sphingosine + choline phosphate
-
980% of activity with sphingomyelin in the absence of detergent
-
?
additional information
?
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
exogenous neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
-
additional information
?
-
-
sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion at a step in the fusion process after CD4 engagement, but sphingomyelinase treatment of cells does not influence gp120 binding, HIV-1 attachment, or fluid-phase and receptor-mediated endocytosis, and furthermore, sphingomyelinase treatment does not affect the membrane disposition of the HIV receptor proteins CD4, CXCR4, and CCR5, Smase treatment does not influence Triton X-100 extraction of HIV-1 receptor proteins, overview
-
-
-
additional information
?
-
-
Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
-
-
-
additional information
?
-
-
the enzyme's beta-hairpin site directly binds to gangliosides, especially ganglioside GM3, i,e, NeuAca2-3Galbeta1-4Glcbeta1-1ceramide through a carbohydrate moiety. Binding response of the enzyme to liposomes containing GM3 is about 15fold higher than that to liposomes lacking GM3. Residues Trp-284 and Phe-285 in the beta-hairpin play an important role in the interaction with GM3
-
-
-
additional information
?
-
-
the enzyme's beta-hairpin site directly binds to gangliosides, especially ganglioside GM3, i,e, NeuAca2-3Galbeta1-4Glcbeta1-1ceramide through a carbohydrate moiety. Binding response of the enzyme to liposomes containing GM3 is about 15fold higher than that to liposomes lacking GM3. Residues Trp-284 and Phe-285 in the beta-hairpin play an important role in the interaction with GM3
-
-
-
additional information
?
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
-
-
-
additional information
?
-
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
-
-
-
additional information
?
-
-
SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
-
-
-
additional information
?
-
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
-
-
-
additional information
?
-
the enzyme has no activity against choline-methyl-phosphatidylcholine
-
-
-
additional information
?
-
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
-
-
-
additional information
?
-
-
an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
-
-
-
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
-
additional information
?
-
-
Niemann Pick disease is an autosomal recessive disorder due to the deficit of lysosomal acid sphingomyelinase, which results in intracellular accumulation of sphingomyelin. Identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
-
-
-
additional information
?
-
-
nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
-
-
-
additional information
?
-
-
patients with atopic dermatitis show reduced activities of acid and neutral sphingomyelinase. The reduced acid sphingomyelinase activity may be partially responsible for the reduced content of stratum corneum ceramides. Reduced neutral sphingomyelinase activity may lead to changes in signal transduction, thereby regulating differentiation. The resulting reduction in involucrin could cause the reduced number of covalently bound ceramides in atopic dermatitis
-
-
-
additional information
?
-
-
spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
-
-
-
additional information
?
-
-
UV light-triggered ASMase activation is essentially required for bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac
-
-
-
additional information
?
-
-
a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
-
-
-
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
-
additional information
?
-
-
common polymorphisms of the SMPD1 gene occur in Niemann-Pick disease type A and B, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
-
-
-
additional information
?
-
-
exogenous acidic sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes, which can be prevented by pre-incubation of the cells with GSH-ethyl ester, overview
-
-
-
additional information
?
-
-
exposure to the NO donors promotes an increase in the protein-protein interaction between acidic sphingomyelinase and caspase-3, with aSMase sequestering caspase-3 and preventing its cleavage and inhibiting apoptosis, overview
-
-
-
additional information
?
-
-
many signaling molecules involved in the pathogenesis of intestinal epithelial barrier, such as TNF-alpha or IFN-gamma, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases
-
-
-
additional information
?
-
-
neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors are essentially involved in endothelial nitric oxide synthase activation by tumor necrosis factor alpha, regulation of the pathway, overview
-
-
-
additional information
?
-
-
neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
-
-
-
additional information
?
-
-
reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, different oxidants modulate different enzymes of the ceramide generating machinery to induce apoptosis in airway epithelial cells, overview
-
-
-
additional information
?
-
-
role for nSMase2 in pro-inflammatory responses induced by TNF-alpha as a regulator of adhesion proteins, both p38-alpha MAPK and nSMase2 are involved in the TNF-alpha-stimulated up-regulation of the adhesion proteins vascular cell adhesion molecule-1 and intercellular adhesion molecule-1
-
-
-
additional information
?
-
-
structural-functional properties of its carboxyl-terminus, amino acids 462-629, the carboxyl-terminus of the ASM is crucial for its protein structure, which in turns dictates the enzymatic function and secretion, overview
-
-
-
additional information
?
-
wild-type alkaline sphingomyelinase inhibits colonic tumorigenesis, while enzyme deficiency or aberrant enzyme forms are associated with human liver tumorigenesis, the enzyme activity is increased in cholestatic liver disease excluding primary sclerosing cholangitis, overview
-
-
-
additional information
?
-
-
ASM is necessary for stress-induced cell death
-
-
-
additional information
?
-
-
the specific ligand binding activity of the serotonin1A receptor in membranes isolated from CHO-5-HT1AR cells is increased upon sphingomyelinase treatment (25 or 50 mU/ml) for 90 min in DMEM/F-12 medium under serum free condition
-
-
-
additional information
?
-
-
establishment of a sensitive quantitative assay method using the fluorescent substrate BODIPY-FL-C12-SM, i.e. N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, D-7711
-
-
-
additional information
?
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
-
a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
-
-
-
additional information
?
-
-
modification of the SMase/SM-synthase balance, shown in the nuclei 1 h after serum deprivation, appears specific for the early events of the apoptotic process
-
-
-
additional information
?
-
-
SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
-
-
-
additional information
?
-
-
spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
-
-
-
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
-
additional information
?
-
-
ASMase inhibition decreases ceramide generation during ischemia/reperfusion, and attenuates serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation, overview, the enzyme is involved in hepatic ischemia/reperfusion damage, ceramide generated from ASMase plays a key role in I/R-induced liver damage, molecular mechanisms, overview
-
-
-
additional information
?
-
-
ASMase activity is required for an efficient fusion of late phagosomes with lysosomes including the efficient transfer of lysosomal hydrolases into phagosomes containing Listeria monocytogenes
-
-
-
additional information
?
-
-
Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
-
-
-
additional information
?
-
-
Src kinase-dependent phosphorylation of p38 MAPK is involved in P2X7-induced A-SMase activation, A-SMase mediates ATP receptor P2X7R-dependent microparticle shedding and P2X7-dependent IL-1beta release
-
-
-
additional information
?
-
-
establishment of a sensitive quantitative assay method using the fluorescent substrate BODIPY-FL-C12-SM, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosyl phosphocholine, or D-7711
-
-
-
additional information
?
-
-
The sphingomyelinase, but not the phospholipase C activity, is essential for induction of hot-cold hemolysis in human erythrocytes, that contain both phosphatidylcholine and sphingomyelin but also in goat erythrocytes, which lack phosphatidylcholine, however, in horse erythrocytes, with a large proportion of phosphatidylcholine and almost no sphingomyelin, hot-cold hemolysis induced by PlcHR2 is not observed, overview. Sphingomyelinase activity gives rise to the formation of ceramide-rich, rigid membrane domains that are resistant to Triton X-100 solubilization
-
-
-
additional information
?
-
-
PlcHR2 toxin from Pseudomonas aeruginosa is an enzyme with both phospholipase C and sphingomyelinase activities, PlcHR2 hydrolyzes phosphatidylcholine and sphingomyelin at similar rates, but other phospholipids are cleaved at much lower rates, if at all
-
-
-
additional information
?
-
-
caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
-
-
-
additional information
?
-
-
expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
-
-
-
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
-
additional information
?
-
-
neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
-
-
-
additional information
?
-
-
a phosphatidylcholine/sphingomyelin metabolism crosstalk which regulates the intranuclear ceramide/diacylglycerol pool exists in the chromatin structure, effect of phosphatidylcholine-specific phospholipase C activity on neutral sphingomyelinase and reverse sphingomyelin synthase, which enrich the intranuclear ceramide pool, overview
-
-
-
additional information
?
-
-
aging in rats causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2, NSMase-2 is both required and sufficient for the onset of IL-1beta hyperresponsiveness during aging, overview
-
-
-
additional information
?
-
-
Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
-
-
-
additional information
?
-
-
neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats and is a key event in glutathione repletion, overview
-
-
-
additional information
?
-
-
the enzyme is involved in sphingomyelin digestion
-
-
-
additional information
?
-
-
key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
-
-
-
additional information
?
-
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
-
-
-
additional information
?
-
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
-
additional information
?
-
Streptomyces griseocarneus NBRC13471
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
-
additional information
?
-
Streptomyces griseocarneus NBRC13471
-
no activity towards 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
-
-
-
additional information
?
-
substrate specificity, the enzyme is highly sphingomyelin-specific, it may not have sphingomyelinase D activity, because it does not hydrolyze the ester linkage between ceramide phosphate and choline. Of the phospholipids tested, the enzyme hydrolyzes only the ester linkage between ceramide and phosphocholine and has no activity toward phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine and phosphatidylinositol
-
-
-
additional information
?
-
substrate specificity, the enzyme is highly sphingomyelin-specific, it may not have sphingomyelinase D activity, because it does not hydrolyze the ester linkage between ceramide phosphate and choline. Of the phospholipids tested, the enzyme hydrolyzes only the ester linkage between ceramide and phosphocholine and has no activity toward phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine and phosphatidylinositol
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
phosphatidylethanolamine + H2O
diacylglycerol + ethanolamine phosphate
-
low activity
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
E9LUE7, E9LUE8, E9LUE9, P17405
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine, ceramide colocalizes with acetylated tubulin in primary cilia and the mitotic spindle of human embryonic stem cells
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
P59116
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
P59116
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
Q9JJY3
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
-
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
I4DXK5
-
a ceramide is an N-acylsphingosine
-
?
a sphingomyelin + H2O
a ceramide + phosphocholine
I4DXK5
-
a ceramide is an N-acylsphingosine
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-activating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate
-
the enzyme cleaves the phosphocholine head group from platelet-activating factor. Potential protective effect of the enzyme against inflammatory bowel disease and colon cancer
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
platelet-inactivating factor + H2O
1-O-alkyl-2-acetyl-sn-glycerol + choline phosphate + ?
-
alk-SMase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity, alk-SMase cleaves the phosphocholine head group from PAF and generates 1-O-alkyl-2-acetyl-sn-glycerol
-
-
?
sphingomyelin + H2O
?
-
-
135146, 135147, 135148, 135149, 135150, 135153, 135156, 135159, 135160, 135161, 135168, 135169, 135187
-
-
?
sphingomyelin + H2O
?
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
cholesterol activation of sphingomyelinase and the strong affinity of cholesterol for sphingomyelin allows the rapid, localized and self-contained production of the metabolic signal ceramide in specific microdomains
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the rapid insect toxicity of sphingomyelinase C results from its phospholipid degrading activity
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
changes in the initial composition and topography of mixed monolayers of sphingomyelin and ceramide modulate the sphingomyelin degradation by the enzyme, overview, the enzyme in an extracellular toxin that exhibits potent hemolytic activity against sphingomyelin-rich erythrocytes in mammals
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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
-
Smase cleaves sphingomyelin at the outer leaflet of the plasma membrane, generating phosphocholine and ceramide
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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
-
acid sphingomyelinase is involved in ceramide signaling, which is important in the lipid raft clustering and formation of redox signaling platform in cell membranes, overview, reactive oxygen species derived from ASM/ceramide triggered lipid raft redox signaling platforms can feedback regulate the ASM activity, FasL-induced O2- may be involved in this regulatory mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Q9BDR3
the enzyme is important in the ceramide catabolism, overview
-
-
ir
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma. Mutations of the enzyme found in colon cancer cells. IN the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
acid SMase is involved in colonic cancer development and apoptosis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview, dietary SM inhibits colonic carcinogenesis by a mechanism related to SM digestion in the gut, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ASMase is required for phorbol 12-myristate 13-acetate-induced ceramide formation involving protein kinase Cdelta, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
degradation of sphingomyelin
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ex vivo redox regulation of nSMase-1 activity in HEK293 cells through a redox GSH-dependent mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
exogenous sphingomyelinase causes impaired intestinal epithelial barrier function, Caco-2 cell monolayers are used as in vitro model for the intestinal barrier, exogenous sphingomyelinase increases transepithelial permeability and decreases transepithelial resistance at concentrations as low as 0.01 U/ml, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
intestinal alkaline sphingomyelinase hydrolyses sphingomyelin to generate ceramide in the intestinal tract, it may protect the intestinal mucosa from inflammation and tumorigenesis, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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
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
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
secretory sphingomyelinase is upregulated in chronic heart failure, S-SMase further correlates with reduced skeletal quadriceps muscle strength as well as impaired peripheral vasodilator capacity, physiological function and parameters of S-SMase in heart tissue, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the alkaline sphingomyelinase together with the neutral ceramidase catalyzes the hydrolysis of endogenous sphingomyelin and milk sphingomyelin in milk-fed infants, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is involved in ceramide signaling, enzyme regulation and ceramide metabolism with galectin-I signaling, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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
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
-
A-SMase in the outer epidermis is essential for basal permeability function, A-SMase activity in the lower epidermis is involved in basal permeability barrier homeostasis
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
Alk-SMase activity decreases with age, both Alk-SMase and N-CDase play a role in the regulation of cholesterol absorption in the small intestine, as the sphingosine in the gut is a product of a concerted action of these two enzymes, mechanism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium, Salmonella infection reduces ASM activity, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
nSMase2 is the key enzyme involved in apoptosis and stress-induced ceramide production by sphingomyelin hydrolysis, enzyme and ceramide signaling pathway regulation, the plasma membrane redox system is involved in regulation of the enzyme, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
the enzyme is important in ceramide metabolism, overview
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
SMase C causes hemolysis and thus is suspected to be a potential virulence factor
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
-
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
Q9ET64
-
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
ceramide production by neutral sphingomyelinase is a key mediator in the induction of inducible nitric oxide synthase
-
?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
-
age-related increase in the activity of NSMase-2 is responsible for the interleukin-1beta hyperresponsiveness and a decrease in GSH levels, phenotype, regulation of neutral sphingomyelinase-2 by GSH in oxidative stress in aging-associated inflammation, overview
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?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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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
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?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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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
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?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
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?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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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
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?
sphingomyelin + H2O
N-acylsphingosine + choline phosphate
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neutral sphingomyelinases are considered major candidates for mediating the stress-induced production of ceramide, regulation, physiological, and pathological roles of these proteins, overview
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-
?
additional information
?
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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
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additional information
?
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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
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additional information
?
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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
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additional information
?
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Smase mediates ceramide formation from low density lipoprotein-sphingomyelin
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additional information
?
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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
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additional information
?
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acid sphingomyelinase redox amplification in mediating the formation of lipid raft redox signaling platforms in coronary arterial endothelial cells, overview
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additional information
?
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Q9BDR3
exogenous sphingomyelinase increases collagen and sulfated glycosaminoglycan production by primary articular chondrocytes, phenotype, overview
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additional information
?
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SMase down-regulates type II collagen in articular chondrocytes via activation of the ERK signaling cascade, redistribution of SOX9, and recruitment of c-Fos
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-
additional information
?
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Q4LEU0
neutral SMase 1 participates in an inducible ceramide-mediating, proapoptotic signaling pathway that operates in heat-induced apoptosis in zebrafish embryonic cells
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-
additional information
?
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cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
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-
-
additional information
?
-
-
cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
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additional information
?
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acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor - induced lethal hepatitis
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additional information
?
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an inherited deficiency of this enzymatic activity results in the type A and B forms of Niemann-Pick disease
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additional information
?
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caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
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additional information
?
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Niemann Pick disease is an autosomal recessive disorder due to the deficit of lysosomal acid sphingomyelinase, which results in intracellular accumulation of sphingomyelin. Identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon
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additional information
?
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nSMase2 functions as a growth suppressor in MCF-7 cells, linking confluence to the G0/G1 cell cycle check point
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additional information
?
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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
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additional information
?
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spingomyelinase induces aggregation and fusion of small very low-density lipoprotein and intermediate-density lipoprotein particles and increases their retention to human arterial proteoglycans
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additional information
?
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UV light-triggered ASMase activation is essentially required for bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac
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additional information
?
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a role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation, regulation, overview
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-
additional information
?
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Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
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-
additional information
?
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common polymorphisms of the SMPD1 gene occur in Niemann-Pick disease type A and B, the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population, overview
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additional information
?
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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
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-
additional information
?
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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
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additional information
?
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many signaling molecules involved in the pathogenesis of intestinal epithelial barrier, such as TNF-alpha or IFN-gamma, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases
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additional information
?
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neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors are essentially involved in endothelial nitric oxide synthase activation by tumor necrosis factor alpha, regulation of the pathway, overview
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additional information
?
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neutral sphingomyelinase inhibition is a key event in glutathione repletion, overview
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additional information
?
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reactive oxygen species, e.g. hydrogen peroxide, specifically activate neutral sphingomyelinase 2 to generate ceramide and induce apoptosis in airway epithelial cells, different oxidants modulate different enzymes of the ceramide generating machinery to induce apoptosis in airway epithelial cells, overview
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additional information
?
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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
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additional information
?
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ASM is necessary for stress-induced cell death
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additional information
?
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the specific ligand binding activity of the serotonin1A receptor in membranes isolated from CHO-5-HT1AR cells is increased upon sphingomyelinase treatment (25 or 50 mU/ml) for 90 min in DMEM/F-12 medium under serum free condition
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additional information
?
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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
?
-
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
-
-
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additional information
?
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a deletion in the gene encoding sphingomyelin phosphodiesterase 3 results in osteogenesis and dentinogenesis imperfecta in the mouse
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additional information
?
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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
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additional information
?
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SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the smpd3-null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency
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additional information
?
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spingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis
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additional information
?
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Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
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additional information
?
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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
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additional information
?
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ASMase activity is required for an efficient fusion of late phagosomes with lysosomes including the efficient transfer of lysosomal hydrolases into phagosomes containing Listeria monocytogenes
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additional information
?
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Pseudomonas aeruginosa-induced cell death involves Asm activation and ceramide generation
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additional information
?
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Src kinase-dependent phosphorylation of p38 MAPK is involved in P2X7-induced A-SMase activation, A-SMase mediates ATP receptor P2X7R-dependent microparticle shedding and P2X7-dependent IL-1beta release
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additional information
?
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The sphingomyelinase, but not the phospholipase C activity, is essential for induction of hot-cold hemolysis in human erythrocytes, that contain both phosphatidylcholine and sphingomyelin but also in goat erythrocytes, which lack phosphatidylcholine, however, in horse erythrocytes, with a large proportion of phosphatidylcholine and almost no sphingomyelin, hot-cold hemolysis induced by PlcHR2 is not observed, overview. Sphingomyelinase activity gives rise to the formation of ceramide-rich, rigid membrane domains that are resistant to Triton X-100 solubilization
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additional information
?
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caspase 8 activates neutral sphingomyelinase in rafts in oligodendrocytes
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additional information
?
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expression of neutral sphingomyelinase-2 in primary rat hepatocytes modulates IL-beta-induced JNK activation
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additional information
?
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key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
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additional information
?
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neutral sphingomyelinase is a key component of the signaling pathway in cytokine- and other stress-induced cellular responses
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additional information
?
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a phosphatidylcholine/sphingomyelin metabolism crosstalk which regulates the intranuclear ceramide/diacylglycerol pool exists in the chromatin structure, effect of phosphatidylcholine-specific phospholipase C activity on neutral sphingomyelinase and reverse sphingomyelin synthase, which enrich the intranuclear ceramide pool, overview
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additional information
?
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aging in rats causes hepatic hyperresponsiveness to interleukin-1beta which is mediated by neutral sphingomyelinase-2, NSMase-2 is both required and sufficient for the onset of IL-1beta hyperresponsiveness during aging, overview
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additional information
?
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Alk-SMase reduces the lysophosphatidic acid formation by hydrolyzing lysophosphatidylcholine to monoacylglycerol, potential biological functions, overview
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additional information
?
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neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats and is a key event in glutathione repletion, overview
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additional information
?
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the enzyme is involved in sphingomyelin digestion
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additional information
?
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key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. The enzyme is a contributor to the increased stress and inflammatory sensitivity amoung the brain regions with age
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additional information
?
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cytotoxic action of bacterial SMases by their hemolytic activity to human erythrocytes, occuring through hydrolysis of the erythrocyte cell surface sphingomyelin, the hemolytic activity of bacterial SMases is increased by cooperative and synergistic interactions among virulence factors secreted by the same bacteria, cytotoxic mechanism, overview
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
Cu2+
Fe2+
KCl
Mg2+
Mn2+
Sr2+
Zn2+
additional information
Ca2+
Km: 0.0191 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Ca2+
-
activated by micromolar concentrations of Ca2+ (0.0001 or 0.00001 mM) under Mg2+-free conditions, ceramide generation is dependent upon the calcium ionophore A23187, nSMase is not activated by Ca2+ cations in the presence of 1 mM Mg2+
Co2+
-
rank-order of increasing activation: Mg2+, Co2+, Mn2+, Zn2+. The four metal ions compete with each other for the same binding site on the enzyme molecule
Co2+
Km: 0.142 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+. There are three distinct metal ion-binding sites in a long horizontal cleft across the bc-SMase molecule
Mg2+
-
two-step activation, high-affinity binding site with 50% saturation at 0.0041 mM, low-affinity-binding site with 50% saturation at 20 mM, approx. 5fold activation at 20 mM
Mg2+
-
rank-order of increasing activation: Mg2+, Co2+, Mn2+, Zn2+. The four metal ions compete with each other for the same binding site on the enzyme molecule
Mg2+
Km: 0.0161 mM, activation of sphingomyelinase activity in the order of decreasing efficiency Co2+, Mn2+, Mg2+, Ca2+, Sr2+
Mg2+
required by N-SMase for activity, residues Glu53, Asp126, Asp295, and His296 are critical for Mg2+ binding and catalytic activity
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+
-
approx. 2fold activation of T-mSMase isoforms delta and gamma at 1 mM and 5 mM, respectively, both S-mSMase isoforms epsilon and zeta require 5 mM Mg2+ for maximal activity
Mg2+
required by nSMase1 for activity; required by N-SMase for activity
Mg2+
dependent on, isozyme Sph2 is unique and possesses the Mg2+-binding Glu53 residue in the metal-binding site
Mg2+