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Information on EC 2.7.8.27 - sphingomyelin synthase and Organism(s) Homo sapiens and UniProt Accession Q86VZ5
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2.7.8.27 sphingomyelin synthaseIUBMB Comments
The reaction can occur in both directions . This enzyme occupies a central position in sphingolipid and glycerophospholipid metabolism . Up- and down-regulation of its activity has been linked to mitogenic and pro-apoptotic signalling in a variety of mammalian cell types . Unlike EC 2.7.8.3, ceramide cholinephosphotransferase, CDP-choline cannot replace phosphatidylcholine as the donor of the phosphocholine moiety of sphingomyelin .
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Word Map
- 2.7.8.27
- sphingolipids
- sphingomyelinase
- diacylglycerol
- glucosylceramide
-
microdomains
- ceramidase
-
phosphatidylcholine-specific
- phosphoethanolamine
- pc-plc
- dihydroceramide
-
2-hydroxyoleic
- cert
- medicine
- tricyclodecan-9-yl-xanthogenate
- analysis
- drug development
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
sphingomyelin synthase, sm synthase, sgms1, sphingomyelin synthase 1, sphingomyelin synthase 2, sgms2, sphingomyelin-synthase, sm synthase 1, sphingomyelin synthases 1, sphingomyelin synthase-related protein, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SMS1
SMS1
SMS2
sphingomyelin synthase 2
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol
positive feedback mechanism from the products to the reactants, in vivo via protein kinase D and the ceramide transfer protein CERT, modeling
SYSTEMATIC NAME
IUBMB Comments
ceramide:phosphatidylcholine cholinephosphotransferase
The reaction can occur in both directions [3]. This enzyme occupies a central position in sphingolipid and glycerophospholipid metabolism [4]. Up- and down-regulation of its activity has been linked to mitogenic and pro-apoptotic signalling in a variety of mammalian cell types [4]. Unlike EC 2.7.8.3, ceramide cholinephosphotransferase, CDP-choline cannot replace phosphatidylcholine as the donor of the phosphocholine moiety of sphingomyelin [2].
CAS REGISTRY NUMBER
COMMENTARY
58703-97-2
-
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
C17-ceramide + 1,2-dimyristoyl-rac-glycero-3-phosphocholine
C17-sphingomyelin + 1,2-dimyristoyl-rac-glycerol
-
-
-
?
L-alpha-phosphatidylcholine + NBD-C6-ceramide
?
i.e. N-(6-[(7-nitro-benz-2-oxa-1,3-diazo-4-yl)amino]caproyl)-ceramide
-
-
?
phosphatidylcholine + C6-ceramide
C6-sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + C8-ceramide
C7-sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
C17-ceramide + 1,2-dimyristoyl-rac-glycero-3-phosphocholine
C17-sphingomyelin + 1,2-dimyristoyl-rac-glycerol
-
-
-
?
L-alpha-phosphatidylcholine + N-(6-[(7-nitro-benz-2-oxa-1,3-diazo-4-yl)amino]caproyl)-ceramide
?
-
i.e. NBD-C6-ceramide
-
-
?
L-alpha-phosphatidylcholine + NBD-C6-ceramide
?
i.e. N-(6-[(7-nitro-benz-2-oxa-1,3-diazo-4-yl)amino]caproyl)-ceramide
-
-
?
phosphatidylcholine + C6-NBD-ceramide
?
-
i.e. N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphingosine, the fluorogenic derivative of C6-ceramide
-
-
?
phosphatidylcholine + C8-ceramide
C7-sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
r
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
substrate C6-NBD-ceramide, molecular docking studies and interaction modes of phosphatidylcholine with the active site of SMS1, overview
detection and quantifcation of C6-NBD-sphingomyelin by HPLC using the reversed-phase C18 column and an isocratic elution with methanol/water/trifluoroacetic acid (89:11:0.1 (v/v))
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
ceramide + phosphatidylcholine
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
-
?
ceramide + phosphatidylcholine
sphingomyelin + 1,2-diacyl-sn-glycerol
-
the enzyme restores homeostasis between sphingomyelin and ceramide pools
-
-
?
phosphatidylcholine + C6-ceramide
C6-sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
-
?
phosphatidylcholine + C6-ceramide
C6-sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
sphingomyelin measurement via a four-step enzymatic process involving sphingomyelinase and histochemic detection
-
-
?
additional information
?
-
-
sphingomyelin measurement via a four-step enzymatic process involving sphingomyelinase and histochemic detection
-
-
?
additional information
?
-
-
both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells, sphingomyelin synthesis plays a critical role in cell growth and survival, overview
-
-
?
additional information
?
-
-
membrane sphingomyelin is a key component of lipid rafts involved in TCR signal transduction, physiological functions of sphingomyelin, overview
-
-
?
additional information
?
-
-
SMS1 converts de novo ceramide into sphingomyelin, overview
-
-
?
additional information
?
-
-
SMS1 suppresses ceramide production and apoptosis post-photodamage
-
-
?
additional information
?
-
-
SMS2 regulates sphingomyelin levels in plasma membrane and lipid rafts and has a potential to regulate NFkappaB activation, via multiple mechanisms, overview
-
-
?
additional information
?
-
-
sphingomyelin plays a very important role both in cell membrane formation, inhibition of sphingomyelin synthase affects intracellular sphingomyelin accumulation and plasma membrane lipid organization, overview
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
-
sphingomyelin synthases regulate production of diacylglycerol at the Golgi apparatus. Downregulation or up-regulation of SMS1 or SMS2 reduces or enhances de novo synthesis of sphingomyelin, pathway regulation, overview
-
-
?
additional information
?
-
-
SMSr proteins display ceramide phosphoethanolamine synthase activity, SMSr produces only trace amounts of ceramide phosphoethanolamine, i.e., 300fold less than SMS1-derived sphingomyelin
-
-
?
additional information
?
-
-
sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
r
ceramide + phosphatidylcholine
sphingomyelin + 1,2-diacyl-sn-glycerol
-
the enzyme restores homeostasis between sphingomyelin and ceramide pools
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
-
both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells, sphingomyelin synthesis plays a critical role in cell growth and survival, overview
-
-
?
additional information
?
-
-
membrane sphingomyelin is a key component of lipid rafts involved in TCR signal transduction, physiological functions of sphingomyelin, overview
-
-
?
additional information
?
-
-
SMS1 converts de novo ceramide into sphingomyelin, overview
-
-
?
additional information
?
-
-
SMS1 suppresses ceramide production and apoptosis post-photodamage
-
-
?
additional information
?
-
-
SMS2 regulates sphingomyelin levels in plasma membrane and lipid rafts and has a potential to regulate NFkappaB activation, via multiple mechanisms, overview
-
-
?
additional information
?
-
-
sphingomyelin plays a very important role both in cell membrane formation, inhibition of sphingomyelin synthase affects intracellular sphingomyelin accumulation and plasma membrane lipid organization, overview
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
sphingomyelin synthase sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce sphingomyelin and diacylglycerol, thereby regulating lipid messengers which play a role in cell survival and apoptosis
-
-
?
additional information
?
-
-
sphingomyelin synthases regulate production of diacylglycerol at the Golgi apparatus. Downregulation or up-regulation of SMS1 or SMS2 reduces or enhances de novo synthesis of sphingomyelin, pathway regulation, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
inhibitor of isoform SGMS2 with good selectivity against SGMS1
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
150fold selectivity for isoform SGMS2 over SGMS1
1-methylcyclopropyl 4-(3-((3-((3-methoxy-5-(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
inhibitor of isoform SGMS2 with good selectivity against SGMS1
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(2-(trifluoromethoxy)phenyl)acetamide
-
4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
inhibitor of isoform SGMS2 with good selectivity against SGMS1
4-(3-(benzyloxy)pyrrolidin-1-yl)-N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
inhibitor of isoform SGMS2 with good selectivity against SGMS1
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-((2-phenylpyridin-4-yl)methoxy)-1,2-dihydroquinoline-3-carboxamide
880fold selectivity for isoform SGMS2 over SGMS1
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
inhibitor of isoform SGMS2 with good selectivity against SGMS1
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(pyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide
more than 100fold selectivity for isoform SGMS2 over SGMS1
N-(4-fluoro-2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
inhibitor of isoform SGMS2 with good selectivity against SGMS1
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
inhibitor of isoform SGMS2 with good selectivity against SGMS1
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
-
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
150fold selectivity for isoform SGMS2 over SGMS1. The interaction with SGMS2 requires the presence of the amino acids S227 and H229, which are located in the catalytic domain of SMS2
1-methylcyclopropyl 4-(3-((3-((3-methoxy-5-(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
potent and selective inhibitor of isoform SGMS2. A repeated treatment in mice leads to significant reduction in hepatic sphingomyelin levels
2-((2-ethylbenzyl)oxy)-N-(pyridin-3-yl)benzamide
selectivity ratio is more than 1400fold for purified isoform SGMS2 over SGMS1. The compound dose-dependently diminishes apoB secretion from Huh7 cells, and significantly reduces the SGMS activity and increases cholesterol efflux from macrophages. It inhibits the secretion of LPS-mediated pro-inflammatory cytokine and chemokine in macrophages. In C57BL/6J mice, the compound is orally efficacious.
2-[[2-((5-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)pentyl)oxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
compound shows dual activity against both phospholipase A2 and sphingomyelin synthase
2-[[2-((6-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)hexyl)oxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
-
2-[[2-(3-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)propoxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
-
2-[[2-(4-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)butoxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
-
4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
-
4-(3-(benzyloxy)pyrrolidin-1-yl)-N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
-
lysenin
-
is a sphingomyelin-directed cytolysin purified from the earthworm, which specifically binds to membrane sphingomyelin and induces pore formation in the plasma membrane and subsequent cell death
-
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-((2-phenylpyridin-4-yl)methoxy)-1,2-dihydroquinoline-3-carboxamide
880fold selectivity for isoform SGMS2 over SGMS1
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
-
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(pyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide
more than 100fold selectivity for isoform SGMS2 over SGMS1
N-[(4-bromophenyl)methyl]-2-[4-[(2-phenylethyl)sulfamoyl]phenoxy]acetamide
-
potassium tricyclodecan-9-yl-xanthogenate
-
i.e. D609, decreases enzyme activity an sphingomyelin levels in different human cell lines in vivo
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
-
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
-
tricyclodecan-9-yl-xanthogenate
-
sphingomyelin synthase is a potential target for tricyclodecan-9-yl-xanthogenate (D609) and inhibition of sphingomyelin synthase may contribute to D609-induced cell death via modulation of the cellular levels of ceramide and diacylglycerol
-
additional information
structure-based virtual screening, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as sphingomyelin synthase 1 inhibitors, molecular docking studies and interaction modes of SMS1 inhibitors with the active site of SMS1, overview
-
additional information
-
photosensitizer Pc 4, PDT, induces inhibition of SMS in Jurkat cells
-
additional information
design of dual inhibitors of secretory phospholipase A2 and sphingomyelin synthase by linking or fusing sphingomyelin synthase inhibitor fragment Ly18 (N-pyridine-3-amide moiety) with phospholipase A2 inhibitor fragment (indole-3-acetamide structure) by 3-6 carbon chain
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-2-hydroxyoleic acid
-
a complex dual mechanism of action of 2-hydroxyoleic acid (2OHOA) as potent anti-tumor compound used in membrane lipid therapy (MLT). Only the S-enantiomer is able to activate enzyme SMS in human glioma U118 cells. The anti-tumor efficacy of the S-enantiomer is greater than that of the R-enantiomer, as the former can act through both membrane lipid therapy mechanisms, type-1 and type-2 MLT approaches. Molecular dynamics study indicates that both enantiomers interact similarly with lipid bilayers, molecular dynamics simulation, overview
2-hydroxyoleic acid
-
enzyme activity is 3.6fold higher than in untreated cells after 24 h of treatment with 0.2 mM 2-hydroxyoleic acid. Activity increases 85% after 5 min of treatment
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00538
C8-ceramide
isoform SMS1, in 50 mM TrisHCl (pH 7.4), at 22°C
0.005549
C8-ceramide
isoform SMS1, in 50 mM TrisHCl (pH 7.4), at 22°C
0.006277
C6-ceramide
isoform SMS2, in 50 mM TrisHCl (pH 7.4), at 22°C
0.007235
C6-ceramide
isoform SMS2, in 50 mM TrisHCl (pH 7.4), at 22°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00085
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.001
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.0024
1-methylcyclopropyl 4-(3-((3-((3-methoxy-5-(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.1
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(2-(trifluoromethoxy)phenyl)acetamide
Homo sapiens
pH 7.4, 37°C
0.1
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(o-tolyl)acetamide
Homo sapiens
pH 7.4, 37°C
0.0147
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-phenylacetamide
Homo sapiens
pH 7.4, 37°C
0.1
4-(2-((4-chlorobenzyl)amino)-2-oxoethoxy)-N-(pyridin-4-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.1
4-(2-((4-chlorobenzyl)amino)-2-oxoethoxy)-N-phenethylbenzamide
Homo sapiens
pH 7.4, 37°C
0.0034
4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.015
4-(3-(benzyloxy)pyrrolidin-1-yl)-N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.1
N-(2-cyanophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0142
N-(2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.1
N-(2-nitrophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.014
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-((2-phenylpyridin-4-yl)methoxy)-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.025
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.0156
N-(3-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0092
N-(3-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0021
N-(4-bromobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.1
N-(4-chlorobenzyl)-2-(4-(N-(3-phenylpropyl)sulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.05
N-(4-chlorobenzyl)-2-(4-(N-(4-chlorobenzyl)sulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0052
N-(4-chlorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.1
N-(4-chlorobenzyl)-2-(4-(N-phenylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0066
N-(4-chlorophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.1
N-(4-fluoro-2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0081
N-(4-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0105
N-(4-fluorophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0059
N-(4-methoxybenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.05
N-(4-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.0231
N-benzyl-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.05
N-phenethyl-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
pH 7.4, 37°C
0.01
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.019
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.000047
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.0000065
1-methylcyclopropyl 4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.000045
1-methylcyclopropyl 4-(3-((3-((3-methoxy-5-(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.00099
2-((2,5-dichlorobenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0028
2-((2,5-dimethoxybenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00069
2-((2,6-dichlorobenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00089
2-((2,6-dimethylbenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00067
2-((2-((5-chloropentyl)oxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00047
2-((2-((6-chlorohexyl)oxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0013
2-((2-(4-chlorobutoxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00074
2-((2-chloro-5-fluorobenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0015
2-((2-chloro-6-fluorobenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0031
2-((3-chloro-2-fluorobenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0038
2-((3-chloro-2-methylbenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0116
2-((5-chloro-2-(2-methoxyethoxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0041
2-((5-chloro-2-(3-methoxypropoxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00043
2-((5-chloro-2-(heptyloxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00052
2-((5-chloro-2-(hexyloxy)benzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00067
2-((5-chloro-2-methoxybenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0011
2-((5-chloro-2-methylbenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00074
2-((5-fluoro-2-methylbenzyl)oxy)-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0017
2-[2-[(2-methylphenyl)methoxy]phenyl][1,3]oxazolo[5,4-b]pyridine
Homo sapiens
pH 7.4, 37°C
0.0253
2-[[2-((5-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)pentyl)oxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0287
2-[[2-((6-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)hexyl)oxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0265
2-[[2-(3-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)propoxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.0617
2-[[2-(4-(3-(2-amino-2-oxoethyl)-5-methoxy-2-methyl-1H-indol-1-yl)butoxy)benzyl]oxy]-N-(pyridin-3-yl)benzamide
Homo sapiens
pH 7.4, 37°C
0.00003
4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.00061
4-(3-(benzyloxy)pyrrolidin-1-yl)-N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.000016
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-((2-phenylpyridin-4-yl)methoxy)-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.00012
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.00095
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(pyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide
Homo sapiens
pH 7.5, 23°C
0.0021
N-(pyridin-3-yl)-2-((2-(trifluoromethyl)benzyl)oxy)benzamide
Homo sapiens
pH 7.4, 37°C
0.0021
N-[(4-bromophenyl)methyl]-2-[4-[(2-phenylethyl)sulfamoyl]phenoxy]acetamide
Homo sapiens
pH 7.4, 37°C
0.00013
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
0.000091
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Homo sapiens
pH 7.5, 23°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
SMS2 mRNA levels are decreased by about 80.67, and protein levels are reduced to approximately 71.33 % in asthenospermia compared to normozoospermia
-
normal and SV40-transformed cells. Increased sphingomyelin synthase activity, possibly due to a plasma-membrane related form of the enzyme, is associated with the SV40-transformed phenotype
additional information
SMS isoform SMS1 is expressed ubiquitously in all the tested tissues
the enzyme SGMS1 expression, but not SGMS2 expression, is significantly elevated in the hippocampus of Alzheimer's disease brains, but not in the cerebellum
-
SMS1 represents a major whereas SMS2 represents a minor SM-synthase activity in HeLa cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
a small portion of SMS2 is found in the perinuclear region
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
inhibition of SGMS activity by siRNA transient transfection or by tricyclodecan-9-yl-xanthogenate (D609) significantly reduces the level of amyloid-beta peptide in a dose and time dependent manner. The decrease in amyloid-beta peptide level occurs without changes in amyloid precursor protein expression or cell viability
physiological function
malfunction
physiological function
additional information
minimal mathematical model for the sphingomyelin synthase 1 (SMS1) driven conversion of ceramide to sphingomyelin based on chemical reaction kinetics, modeling sphingomyelin synthase 1 driven reaction at the Golgi apparatus can explain data by inclusion of a positive feedback mechanism, this model is not able to qualitatively reproduce experimental measurements on lipid compositions after altering SMS1 activity, overview
physiological function
enzyme SGMS activity impacts on amyloid precursor protein processing to produce amyloid-beta peptide and it seems to be a contributing factor in amyloid-beta peptide pathology associated with Alzheimer's disease. SGMS1 activity regulates amyloid precursor protein processing and not production
physiological function
role of SMSs in vesicular trafficking from the Golgi to the plasma membrane
malfunction
-
down-regulation of isoform SMS1 and SMS2 reduces the localization of the DAG-binding protein, protein kinase D to the Golgi
malfunction
-
inhibition of sphingomyelin synthase activity profoundly impairs the killing ability of neutrophils against Cryptococcus neoformans by preventing the extracellular release of an antifungal factors
physiological function
-
isoforms SMS1 and SMS2 are key factors in the control of sphingomyelin and 1,2-diacyl-sn-glycerol levels within the cell and thus influence apoptosis
physiological function
-
isoform SMS1 and SMS2 are capable of regulating trans golgi network-mediated protein trafficking and secretion. Both isoform activities are critical to retain the correct morphology of both cis-Golgi and trans golgi network
physiological function
-
isoform SMS2 over-expression is probably associated with increased expression of aortic inflammatory biomarkers, as well as decreased numbers of CD34/kinase-insert domain-positive cells, circulating angiogenic cells and colony-forming units in circulation. Therefore, SMS2 over-expression might correlate with endothelial dysfunction and aggravate atherosclerotic plaque instability in ApoE knockout mice
physiological function
-
the enzyme plays a key role in the regulation of the killing activity of neutrophils against Cryptococcus neoformans through a diacylglycerol-protein kinase D dependent mechanism
physiological function
-
the Sms1 gene is a downstream target of Bcr-abl, involved in sustaining cell proliferation of Bcr-abl-positive cells
physiological function
inhibition of SMS2 activity decreases sperm motility and penetration ability into methylcellulose, but has no influence on capacitation and acrosome reaction, or on intracellular Ca2+ concentration compared to IgG-treated control groups. The phosphorylation level of Akt is decreased, whereas the phosphorylation of ERK and cleaved-caspase 3 levels are significantly increased by SGMS2 inhibition
physiological function
SGMS2 overexpression may promote endothelial cell dysfunction by activating the Wnt/beta-catenin signaling pathway. SGMS2 overexpression promotes apoptosis and macrophage adhesion of H2O2-induced endothelial cells, thereby increasing the expression of beta-catenin. SGMS inhibitor Dy105 may inhibit the evolution of oxidative stress-induced dysfunction
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SMS1_HUMAN
413
6
48617
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
SMS isozyme domain structure and active site comformation, tertiary structure model by homology modeling, overview
additional information
SMS isozyme domain structure and active site comformation, tertiary structure model by homology modeling, overview
additional information
SMS isozyme domain structure and active site comformation, tertiary structure model by homology modeling, overview
additional information
SMS isozyme domain structure and active site comformation, tertiary structure model by homology modeling, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
SMS2 is palmitoylated at cysteine residues via thioester bonds in the COOH-terminal cytoplasmic tail, SMS1 is not palmitoylated
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H285A
site-directed mutagenesis, inactive mutant with wild-type localization pattern, overview. The point mutation only influences SMS2 catalytic activity but not the enzyme topology
H328A
site-directed mutagenesis, inactive mutant with wild-type localization pattern, overview. The point mutation only influences SMS2 catalytic activity but not the enzyme topology
H332A
site-directed mutagenesis, inactive mutant with wild-type localization pattern, overview. The point mutation only influences SMS2 catalytic activity but not the enzyme topology
S273A
site-directed mutagenesis, inactive mutant with wild-type localization pattern, overview. The point mutation only influences SMS2 catalytic activity but not the enzyme topology
S283A
site-directed mutagenesis, inactive mutant with wild-type localization pattern, overview. The point mutation only influences SMS2 catalytic activity but not the enzyme topology
additional information
additional information
construction of an SMS1 interference vector, enzyme silencing by shRNA in Hep-G2 cells leading a downregulation rate of 45% and reduced enzyme activity of 56%
additional information
construction of an SMS1 interference vector, enzyme silencing by shRNA in Hep-G2 cells leading a downregulation rate of 45% and reduced enzyme activity of 56%
additional information
-
downregulation of SMS in Huh7 cells by expression of siRNA, overview
additional information
-
downregulation of SMS1 or SMS2 by siRNA oligonucleotides targeting SMS1 or SMS2 in HeLA cells reduces de novo synthesis of sphingomyelin, overview
additional information
-
endogenous SMS2 expression in HeLa cells is reduced by about 80% after treatment with SMS2 siRNA, but is unaffected after treatment with lamin A or SMS1 siRNAs. Impact of SMS1 and SMS2 depletion on the lipid composition of HeLa cells, overview
additional information
-
knockout of SMS1 in T-cells by transfection of SMS1-short-interfering RNA into Jurkat T cells, impaired TCR signaling through dysfunction of lipid rafts in SMS1-knockdown T cells, overview. CD3-induced tyrosine phosphorylation and association of linker for activation of T cell with ZAP-70 and Grb2 and phosphorylation of protein kinase C are also severely impaired in Jurkat-SMS1/kd cells
additional information
-
overexpression of SMS1 in Jurkat cells leads to suppression of the production of dihydroceramides and dihydrosphingosine, and ceramide
additional information
-
overexpression of SMS1 is accompanied by attenuated ceramide response and apoptotic resistance after photodamage with the photosensitizer Pc 4, while suppression of SMS1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage, overview
additional information
-
sphingomyelin synthase 2 deficiency, due to siRNA treatment of HEK-293 cells, attenuates NFkappaB activation, it impairs TNF receptor 1 recruitment tolipid rafts and TLR4-MD2 complex recruitment to plasma membrane
additional information
construction of an SMS2 interference vector, enzyme silencing by shRNA in Hep-G2 cells leading to a downregulation rate of 67% and reduced enzyme activity of 63%
additional information
construction of an SMS2 interference vector, enzyme silencing by shRNA in Hep-G2 cells leading to a downregulation rate of 67% and reduced enzyme activity of 63%
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression analysis of isozymes SMS1 and SMS2 by RT-PCR, recombinant overexpression of isozymes SMS1 and SMS2 in HeLa cells
-
overexpression of FLAG-tagged SMS1 or FLAG-tagged SMS2 in HeLa cells enhances de novo synthesis of sphingomyelin. expression of SMS1 and SMS2 viaSV40-transformation of WI38 fibroblasts, subcellular localization study, overview
-
SMS1 and SMS2 expression levels, quatitative determination by Real-time PCT analysis, overview
-
stable overexpression of SMS1 in Jurkat cells leading to a 3.8fold increase in SMS activity
-
transient expression of Flag-tagged wild-type SMS2 and mutants in HeLa cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme inhibition or down-regulation of SMS1 expression by siRNA selectively inhibits the proliferation of Bcr-abl-positive cells
-
isoform SMS1 is highly elevated (approximately 10fold) in K-562 chronic myelogenous leukemia cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
-
sphingomyelin synthase is a potential target for tricyclodecan-9-yl-xanthogenate (D609) and inhibition of sphingomyelin synthase may contribute to D609-induced cell death via modulation of the cellular levels of ceramide and diacylglycerol
drug development
enzyme SMS1 is a drug target for the treatment of atherosclerosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vivekananda, J.; Smith, D.; King, R.J.
Sphingomyelin metabolites inhibit sphingomyelin synthase and CTP:phosphocholine cytidylyltransferase
Am. J. Physiol.
281
L98-L107
2001
Homo sapiens
Albi, E.; La Porta, C.A.; Cataldi, S.; Magni, M.V.
Nuclear sphingomyelin-synthase and protein kinase C delta in melanoma cells
Arch. Biochem. Biophys.
438
156-161
2005
Homo sapiens, Mus musculus
Huitema, K.; van den Dikkenberg, J.; Brouwers, J.F.H.M.; Holthuis, J.C.M.
Identification of a family of animal sphingomyelin synthases
EMBO J.
23
33-44
2004
Caenorhabditis elegans (Q20735), Caenorhabditis elegans (Q9U3D4), Caenorhabditis elegans, Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3), Homo sapiens, Mus musculus (Q8VCQ6), Mus musculus
Meng, A.; Luberto, C.; Meier, P.; Bai, A.; Yang, X.; Hannun, Y.A.; Zhou, D.
Sphingomyelin synthase as a potential target for D609-induced apoptosis in U937 human monocytic leukemia cells
Exp. Cell Res.
292
385-392
2004
Homo sapiens
Luberto, C.; Hannun, Y.A.
Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C?
J. Biol. Chem.
273
14550-14559
1998
Homo sapiens
Yamaoka, S.; Miyaji, M.; Kitano, T.; Umehara, H.; Okazaki, T.
Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells
J. Biol. Chem.
279
18688-18693
2004
Homo sapiens (Q86VZ5), Homo sapiens
Tafesse, F.G.; Ternes, P.; Holthuis, J.C.
The multigenic sphingomyelin synthase family
J. Biol. Chem.
281
29421-29425
2006
Mus musculus, Pseudomonas aeruginosa, Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3)
Hailemariam, T.K.; Huan, C.; Liu, J.; Li, Z.; Roman, C.; Kalbfeisch, M.; Bui, H.H.; Peake, D.A.; Kuo, M.; Cao, G.; Wadgaonkar, R.; Jiang, X.
Sphingomyelin synthase 2 deficiency attenuates NFkappaB activation
Arterioscler. Thromb. Vasc. Biol.
28
1519-1526
2008
Homo sapiens, Mus musculus
Separovic, D.; Hanada, K.; Maitah, M.Y.; Nagy, B.; Hang, I.; Tainsky, M.A.; Kraniak, J.M.; Bielawski, J.
Sphingomyelin synthase 1 suppresses ceramide production and apoptosis post-photodamage
Biochem. Biophys. Res. Commun.
358
196-202
2007
Homo sapiens
Villani, M.; Subathra, M.; Im, Y.B.; Choi, Y.; Signorelli, P.; Del Poeta, M.; Luberto, C.
Sphingomyelin synthases regulate production of diacylglycerol at the Golgi
Biochem. J.
414
31-41
2008
Homo sapiens
Li, Z.; Hailemariam, T.K.; Zhou, H.; Li, Y.; Duckworth, D.C.; Peake, D.A.; Zhang, Y.; Kuo, M.S.; Cao, G.; Jiang, X.C.
Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization
Biochim. Biophys. Acta
1771
1186-1194
2007
Homo sapiens
Yeang, C.; Varshney, S.; Wang, R.; Zhang, Y.; Ye, D.; Jiang, X.C.
The domain responsible for sphingomyelin synthase (SMS) activity
Biochim. Biophys. Acta
1781
610-617
2008
Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3)
Separovic, D.; Semaan, L.; Tarca, A.L.; Awad Maitah, M.Y.; Hanada, K.; Bielawski, J.; Villani, M.; Luberto, C.
Suppression of sphingomyelin synthase 1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage
Exp. Cell Res.
314
1860-1868
2008
Homo sapiens
Jin, Z.X.; Huang, C.R.; Dong, L.; Goda, S.; Kawanami, T.; Sawaki, T.; Sakai, T.; Tong, X.P.; Masaki, Y.; Fukushima, T.; Tanaka, M.; Mimori, T.; Tojo, H.; Bloom, E.T.; Okazaki, T.; Umehara, H.
Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin synthase 1 (SMS1)-knockdown T cells
Int. Immunol.
20
1427-1437
2008
Homo sapiens
Tafesse, F.G.; Huitema, K.; Hermansson, M.; van der Poel, S.; van den Dikkenberg, J.; Uphoff, A.; Somerharju, P.; Holthuis, J.C.
Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells
J. Biol. Chem.
282
17537-17547
2007
Homo sapiens, Mus musculus
Tani, M.; Kuge, O.
Sphingomyelin synthase 2 is palmitoylated at the COOH-terminal tail, which is involved in its localization in plasma membranes
Biochem. Biophys. Res. Commun.
381
328-332
2009
Homo sapiens
Vacaru, A.M.; Tafesse, F.G.; Ternes, P.; Kondylis, V.; Hermansson, M.; Brouwers, J.F.; Somerharju, P.; Rabouille, C.; Holthuis, J.C.
Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER
J. Cell Biol.
185
1013-1027
2009
Homo sapiens
Ding, T.; Li, Z.; Hailemariam, T.; Mukherjee, S.; Maxfield, F.; Wu, M.; Jiang, X.
SMS overexpression and knockdown: Impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosis
J. Lipid Res.
49
376-385
2008
Homo sapiens
Ternes, P.; Brouwers, J.F.; van den Dikkenberg, J.; Holthuis, J.C.
Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase
J. Lipid Res.
50
2270-2277
2009
Homo sapiens
Chen, Y.; Yurek, D.A.; Yu, L.; Wang, H.; Ehsani, M.E.; Qian, Y.W.; Konrad, R.J.; Jiang, X.C.; Kuo, M.S.; Cao, G.; Wang, J.
Development of a quantitative biochemical and cellular sphingomyelin synthase assay using mass spectrometry
Anal. Biochem.
438
61-66
2013
Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3), Homo sapiens
Burns, T.A.; Subathra, M.; Signorelli, P.; Choi, Y.; Yang, X.; Wang, Y.; Villani, M.; Bhalla, K.; Zhou, D.; Luberto, C.
Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene
J. Lipid Res.
54
794-805
2013
Homo sapiens
Zhao, Y.R.; Dong, J.B.; Li, Y.; Wu, M.P.
Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice
Life Sci.
90
867-873
2012
Homo sapiens
Yeang, C.; Ding, T.; Chirico, W.J.; Jiang, X.C.
Subcellular targeting domains of sphingomyelin synthase 1 and 2
Nutr. Metab.
8
89
2011
Homo sapiens (Q86VZ5), Mus musculus (Q9D4B1)
Qureshi, A.; Subathra, M.; Grey, A.; Schey, K.; Del Poeta, M.; Luberto, C.
Role of sphingomyelin synthase in controlling the antimicrobial activity of neutrophils against Cryptococcus neoformans
PLoS ONE
5
e15587
2010
Homo sapiens
Subathra, M.; Qureshi, A.; Luberto, C.
Sphingomyelin synthases regulate protein trafficking and secretion
PLoS ONE
6
e23644
2011
Homo sapiens, Rattus norvegicus
Barcelo-Coblijn, G.; Martin, M.L.; de Almeida, R.F.; Noguera-Salva, M.A.; Marcilla-Etxenike, A.; Guardiola-Serrano, F.; Lueth, A.; Kleuser, B.; Halver, J.E.; Escriba, P.V.
Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy
Proc. Natl. Acad. Sci. USA
108
19569-19574
2011
Homo sapiens
Piotto, S.; Concilio, S.; Bianchino, E.; Iannelli, P.; Lopez, D.J.; Teres, S.; Ibarguren, M.; Barcelo-Coblijn, G.; Martin, M.L.; Guardiola-Serrano, F.; Alonso-Sande, M.; Funari, S.S.; Busquets, X.; Escriba, P.V.
Differential effect of 2-hydroxyoleic acid enantiomers on protein (sphingomyelin synthase) and lipid (membrane) targets
Biochim. Biophys. Acta
1838
1628-1637
2014
Homo sapiens
Li, Y.L.; Qi, X.Y.; Jiang, H.; Deng, X.D.; Dong, Y.P.; Ding, T.B.; Zhou, L.; Men, P.; Chu, Y.; Wang, R.X.; Jiang, X.C.; Ye, D.Y.
Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors
Bioorg. Med. Chem.
23
6173-6184
2015
Homo sapiens (Q86VZ5)
Hu, S.; Ding, Y.; Song, D.; Chen, Q.; Yan, N.
Construction and identification of RNA interference vector of human sphingomyelin synthase
Fudan Univ. J. Med. Sci.
40
584-588
2013
Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3)
-
Thomaseth, C.; Weber, P.; Hamm, T.; Kashima, K.; Radde, N.
Modeling sphingomyelin synthase 1 driven reaction at the Golgi apparatus can explain data by inclusion of a positive feedback mechanism
J. Theor. Biol.
337
174-180
2013
Homo sapiens (Q86VZ5)
Hsiao, J.H.; Fu, Y.; Hill, A.F.; Halliday, G.M.; Kim, W.S.
Elevation in sphingomyelin synthase activity is associated with increases in amyloid-beta peptide generation
PLoS ONE
8
e74016
2013
Homo sapiens (Q86VZ5), Homo sapiens
Yukawa, T.; Nakahata, T.; Okamoto, R.; Ishichi, Y.; Miyamoto, Y.; Nishimura, S.; Oikawa, T.; Kubo, K.; Adachi, R.; Satomi, Y.; Nakakariya, M.; Amano, N.; Kamaura, M.; Matsunaga, N.
Discovery of 1,8-naphthyridin-2-one derivative as a potent and selective sphingomyelin synthase 2 inhibitor
Bioorg. Med. Chem.
28
115376
2020
Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3), Mus musculus (Q9D4B1)
Adachi, R.; Ogawa, K.; Matsumoto, S.; Satou, T.; Tanaka, Y.; Sakamoto, J.; Nakahata, T.; Okamoto, R.; Kamaura, M.; Kawamoto, T.
Discovery and characterization of selective human sphingomyelin synthase 2 inhibitors
Eur. J. Med. Chem.
136
283-293
2017
Homo sapiens (Q86VZ5), Homo sapiens (Q8NHU3), Homo sapiens
Li, Y.; Huang, T.; Lou, B.; Ye, D.; Qi, X.; Li, X.; Hu, S.; Ding, T.; Chen, Y.; Cao, Y.; Mo, M.; Dong, J.; Wei, M.; Chu, Y.; Li, H.; Jiang, X.; Cheng, N.; Zhou, L.
Discovery, synthesis and anti-atherosclerotic activities of a novel selective sphingomyelin synthase 2 inhibitor
Eur. J. Med. Chem.
163
864-882
2019
Homo sapiens (Q8NHU3)
Zhang, P.; Hua, L.; Hou, H.; Du, X.; He, Z.; Liu, M.; Hu, X.; Yan, N.
Sphingomyelin synthase 2 promotes H2O2-induced endothelial dysfunction by activating the Wnt/beta-catenin signaling pathway
Int. J. Mol. Med.
42
3344-3354
2018
Homo sapiens (Q8NHU3)
Gong, H.; Zhou, L.; Ye, D.; Gao, X.; Li, Y.; Qi, X.; Chu, Y.
Novel dual inhibitors of secretory phospholipase A2 and sphingomyelin synthase Design, synthesis and evaluation
Lett. Drug Des. Discov.
13
1025-1032
2016
Homo sapiens (Q8NHU3)
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