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Information on EC 2.7.8.27 - sphingomyelin synthase
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EC Tree
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 expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
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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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
phosphatidylcholine:ceramide cholinephosphotransferase 1
phosphatidylcholine:ceramide cholinephosphotransferase 2
SGMS1
Sgms2
SM synthase
SMS
SMS1
SMS2
sphingomyelin synthase 1
sphingomyelin synthase 2
sphingomyelin-synthase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
-
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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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].
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CAS REGISTRY NUMBER
COMMENTARY
58703-97-2
-
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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
6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl)-sphingosine + 1,2-dimyristoyl-sn-glycero-3-phosphocholine
N-(N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-epsilon-aminohexanoyl)sphingosylphosphorylcholine + ?
-
-
-
-
?
6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl)sphingosine + phosphatidylcholine
N-hexanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + 1,2-diacylglycerol
-
-
-
?
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
-
-
?
N-(6-((7-nitrobenz-2-oxa-1.3-diazol-4-yl)amino)hexanoyl)-sphingosine + a phosphatidylcholine
N-(6-((7-nitro-2-1,3-benzoxadiazol-4-yl)amino)hexanoyl)-sphingosine-1-phosphocholine + a 1,2-diacyl-sn-glycerol
i.e. C6-NBD-ceramide
i.e. C6-NBD-sphingomyelin or C6-NBDCerPCho
-
?
N-lauroyl-D-erythro-sphingosylphosphorylcholine + N-(6-[(7-nitro-benz-2-oxa-1,3-diazo-4-yl)amino]caproyl)-ceramide
?
-
i.e. lauroyl sphingomyelin and C6-NBD-ceramide
-
-
?
phosphatidylcholine + 6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl)sphingosine
N-hexanoyl-4-nitrobenz-2-oxa-1,3-diazole-sphingomyelin + 1,2-diacylglycerol
-
-
-
-
ir
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))
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 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 + 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
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + diacylglycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + diacylglycerol
SMS2 is crucial to cellular lipid metabolism
-
-
?
additional information
?
-
-
synthesis of N-6[7-nitro-2,1,3-benzoxadiazol-4-yl]aminohexanoyl-phosphatidylcholine on the basolateral cell surface of MDCK cells occurs via the reverse reaction of a sphingomyelin synthase
-
-
?
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
-
-
?
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
?
-
SMS1 not only suppresses the effects of Bax overexpression, but it also blocks the deleterious effects of a number of other stresses, including hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. Sphingomyelin synthase 1 likely prevents cell death by counteracting stress-mediated accumulation of endogenous sphingolipids
-
-
?
additional information
?
-
-
SMS1 not only suppresses the effects of Bax overexpression, but it also blocks the deleterious effects of a number of other stresses, including hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. Sphingomyelin synthase 1 likely prevents cell death by counteracting stress-mediated accumulation of endogenous sphingolipids
-
-
?
additional information
?
-
-
SMS1 is located in the Golgi apparatus, where its two enzymatic products, sphingomyelin and diacylglycerol, play an important role in new lipid raft formation and secretory vesicle formation at the trans-Golgi network for transport to the plasma membrane, sphingomyelin synthesis through SMS1 depends on cholesterol homeostasis. S49AR cells are unable to synthesize sphingomyelin due to downregulated SMS1 expression
-
-
?
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
?
-
development of a HPLC-FLD method for real-time monitoring of relative SMS activity based on the measurement of 6-((N-(7-nitrobenz-2-oxa-1.3-diazol-4-yl)amino)hexanoyl)-sphingosine (C6-NBD-Cer) and 6-((N-(7-nitro-2-1,3-benzoxadiazol-4-yl)amino)hexanoyl)-sphingosine-1-phosphocholine (C6-NBDCerPCho) in plasma, which is then used to assess the SMS inhibitory activity of D2 in vivo, kinetics, overview
-
-
?
additional information
?
-
-
highly purified sphingomyelin synthase preparation also shows neutral sphingomyelinase activity
-
-
?
additional information
?
-
-
SMS2 may play a crucial role in the lipid metabolism in arosome formation and the plasma membrane restructuring from late round spermatids to early elongating spermatids
-
-
?
additional information
?
-
SMS2 may play a crucial role in the lipid metabolism in arosome formation and the plasma membrane restructuring from late round spermatids to early elongating spermatids
-
-
?
additional information
?
-
-
SMS1 is a key enzyme in the sphingomyelin cycle, metabolites of the cycle play an important role in neuronal death after ischemia, mechanism underlying cerebral ischemia, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
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
6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl)-sphingosine + 1,2-dimyristoyl-sn-glycero-3-phosphocholine
N-(N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-epsilon-aminohexanoyl)sphingosylphosphorylcholine + ?
-
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + diacylglycerol
SMS2 is crucial to cellular lipid metabolism
-
-
?
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
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
-
-
-
?
ceramide + phosphatidylcholine
sphingomyelin + 1,2-diacyl-sn-glycerol
-
the enzyme restores homeostasis between sphingomyelin and ceramide pools
-
-
?
additional information
?
-
-
synthesis of N-6[7-nitro-2,1,3-benzoxadiazol-4-yl]aminohexanoyl-phosphatidylcholine on the basolateral cell surface of MDCK cells occurs via the reverse reaction of a sphingomyelin synthase
-
-
?
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
?
-
SMS1 not only suppresses the effects of Bax overexpression, but it also blocks the deleterious effects of a number of other stresses, including hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. Sphingomyelin synthase 1 likely prevents cell death by counteracting stress-mediated accumulation of endogenous sphingolipids
-
-
?
additional information
?
-
-
SMS1 not only suppresses the effects of Bax overexpression, but it also blocks the deleterious effects of a number of other stresses, including hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. Sphingomyelin synthase 1 likely prevents cell death by counteracting stress-mediated accumulation of endogenous sphingolipids
-
-
?
additional information
?
-
-
SMS1 is located in the Golgi apparatus, where its two enzymatic products, sphingomyelin and diacylglycerol, play an important role in new lipid raft formation and secretory vesicle formation at the trans-Golgi network for transport to the plasma membrane, sphingomyelin synthesis through SMS1 depends on cholesterol homeostasis. S49AR cells are unable to synthesize sphingomyelin due to downregulated SMS1 expression
-
-
?
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
?
-
-
SMS2 may play a crucial role in the lipid metabolism in arosome formation and the plasma membrane restructuring from late round spermatids to early elongating spermatids
-
-
?
additional information
?
-
SMS2 may play a crucial role in the lipid metabolism in arosome formation and the plasma membrane restructuring from late round spermatids to early elongating spermatids
-
-
?
additional information
?
-
-
SMS1 is a key enzyme in the sphingomyelin cycle, metabolites of the cycle play an important role in neuronal death after ischemia, mechanism underlying cerebral ischemia, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
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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
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; 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
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-(4-(N-phenethylsulfamoyl)phenoxy)-N-(2-(trifluoromethoxy)phenyl)acetamide
-
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; 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; more than 100fold selectivity for isoform SGMS2 over SGMS1
N-(4-fluoro-2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
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
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-dihydro-1,8-naphthyridin-4-yl)oxy)propyl)piperidine-1-carboxylate
-
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; potent and selective inhibitor of isoform SGMS2. A repeated treatment in mice leads to significant reduction in hepatic sphingomyelin levels
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
-
2-(2-(benzyloxy)phenyl)-2-(phenylamino) acetonitrile
i.e. D2, development of a HPLC-FLD method for real-time monitoring of relative SMS activity based on the measurement of C6-NBD-Cer and C6-NBDCerPCho in plasma, which is then used to assess the SMS inhibitory activity of D2 in vivo, overview
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-((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
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
-
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-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
-
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-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
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
-
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
-
photosensitizer Pc 4, PDT, induces inhibition of SMS in Jurkat cells
-
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
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
-
additional information
-
disturbance of cholesterol homoeostasis by 3-beta-[2-(diethylamino)-ethoxy]androst-5-en-17-one, i.e. U18666A, indirectly inhibits sphingomyelin biosynthesis, overview
-
additional information
turpentine leads to downregulation of SMS1 expression in liver
-
additional information
-
turpentine leads to downregulation of SMS1 expression in liver
-
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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
Thioacetamide
-
thioacetamide-induced increase in microsomal sphingomyelin by a stimulation of sphingomyelin synthase
additional information
-
early response of the SMS1 gene that can be induced by both ischemia and stress
-
additional information
-
induction of SMS2 during Adjudin-induced AJ restructuring and disruption
-
additional information
induction of SMS2 during Adjudin-induced AJ restructuring and disruption
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00749
6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl)-sphingosine
-
at pH 7.4 and 37°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
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
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000003 - 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
0.0000065 - 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
0.0000022 - 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
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
0.1
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
0.0017
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
0.1
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
0.0000077 - 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
0.00061 - 0.015
4-(3-(benzyloxy)pyrrolidin-1-yl)-N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
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
0.000016 - 0.014
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-((2-phenylpyridin-4-yl)methoxy)-1,2-dihydroquinoline-3-carboxamide
0.00012 - 0.025
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
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
0.0156
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
0.0021
N-(pyridin-3-yl)-2-((2-(trifluoromethyl)benzyl)oxy)benzamide
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
0.0021
N-[(4-bromophenyl)methyl]-2-[4-[(2-phenylethyl)sulfamoyl]phenoxy]acetamide
Homo sapiens
pH 7.4, 37°C
0.000032 - 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
0.000019 - 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
0.000003
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
Mus musculus
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
0.00085
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
0.0000065
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
0.001
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
0.0000022
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
Mus musculus
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
0.0024
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
0.0135
2-(2-(benzyloxy)phenyl)-2-(phenylamino) acetonitrile
Mus musculus
SMS2, pH and temperature not specified in the publication
0.0245
2-(2-(benzyloxy)phenyl)-2-(phenylamino) acetonitrile
Mus musculus
SMS in liver homogenate, pH and temperature not specified in the publication
0.0000077
4-(3-((3-((3,5-bis(trifluoromethyl)benzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Mus musculus
pH 7.5, 23°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
0.0034
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
0.00061
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
0.00066
4-(3-(benzyloxy)pyrrolidin-1-yl)-N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide
Mus musculus
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
0.000016
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
0.014
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
0.00012
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
0.00024
N-(3,5-bis(trifluoromethyl)benzyl)-N,1-dimethyl-2-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydroquinoline-3-carboxamide
Mus musculus
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
0.000032
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
Mus musculus
pH 7.5, 23°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
0.01
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
0.000019
tert-butyl 4-(3-((3-((3,5-dimethoxybenzyl)(methyl)carbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)propyl)piperidine-1-carboxylate
Mus musculus
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
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
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9.5
-
pH 7: about 50% of maximal activity, pH 9.5: 65% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
the mouse SMS1 gene is subject to alternative splicing and gives rise to full-length SMS1 as well as two truncated proteins that contain the N-terminal SAM domain and the first two of the six transmembrane domains
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
exports a substantial fraction of sphingomyelin synthase activity to membranes beyond their plasma membrane
brenda
SMS2 mRNA levels are decreased by about 80.67, and protein levels are reduced to approximately 71.33 % in asthenospermia compared to normozoospermia
brenda
expression of SMS2 is limited to late round spermatids and elongating spermatids, not detected in late elongate spermatids. SMS2 associates with the developing acrosome beginning in late round spermatids through elongating spermatids and in the cell membrane. SMS2 may play a crucial role in the plasma membrane restructuring from late round spermatids to early elongating spermatids
brenda
-
exports a substantial fraction of sphingomyelin synthase activity to membranes beyond their plasma membrane
brenda
-
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
brenda
additional information
the enzyme SGMS1 expression, but not SGMS2 expression, is significantly elevated in the hippocampus of Alzheimer's disease brains, but not in the cerebellum
brenda
-
changes in the mRNA expression of the SMS1 gene occur in rats after focal cerebral ischemia. In damaged ipsilateral cortex in the ischemic cortex, the level of SMS1 transcripts is decreased, overview
brenda
-
in cerebellum, isoform SMS1 is barely detectable both in granule and Purkinje cells while SMS2 is markedly expressed in Purkinje cells and inner granule cells
brenda
-
SMS1 represents a major whereas SMS2 represents a minor SM-synthase activity in HeLa cells
brenda
-
in hippocampus, both isoforms SMS1 and SMS2 are expressed in granule cells while SMS2 expression is stronger in dentate gyrus
brenda
moderate expression of SMS1 mRNA. DEcrease in mRNA expression and protein expression following turpentine treatment
brenda
-
only isoform SMS2 proteins localize in neurites of hippocampal neurons
brenda
additional information
SMS isoform SMS1 is expressed ubiquitously in all the tested tissues
brenda
additional information
-
no expression of SMS1 and SMS2 in alkyl-lysophospholipid-resistant S49AR mouse lymphoma cells
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
SMS2 associates with the developing acrosome beginning in late round spermatids through elongating spermatids. SMS2 may play a crucial role in the arosome formation
-
brenda
-
a small portion of SMS2 is found in the perinuclear region
-
brenda
additional information
-
high activity. The presence of sphingomyelin synthase in chromatin may have a relevant influence in regulating the diacylglycerol/ceramide ratio at this particular subcellular level
brenda
-
functional reconstitution of sphingomyelin synthase in Chinese hamster ovary cell membranes
brenda
additional information
-
Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubovesicular network in the cytoplasm of mature erythrocytes
-
brenda
additional information
-
SMS2 topology with intracellular, membrane, and extracellular protein parts, detailed overview, SMS2 tissue expression analysis by immunohistochemistry, immunofluorescence microscopy, and immunogold electron microscopy, overview
-
brenda
additional information
SMS2 topology with intracellular, membrane, and extracellular protein parts, detailed overview, SMS2 tissue expression analysis by immunohistochemistry, immunofluorescence microscopy, and immunogold electron microscopy, overview
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
sphingomyelin synthase (SMS) is the last key enzyme in the sphingosine-1-phosphocholine synthesis process
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
malfunction
-
SMS2 deficiency causes significant induction of cholesterol efflux in vitro and in vivo, SMS2 deficiency in the macrophages reduces atherosclerosis in mice
malfunction
-
down-regulation of isoform SMS1 and SMS2 reduces the localization of the DAG-binding protein, protein kinase D to the Golgi
malfunction
-
down-regulation of isoform SMS1 and SMS2 reduces the localization of the DAG-binding protein, protein kinase D to the Golgi. Inhibition of the enzyme significantly reduces insulin secretion in rat INS-1 cells
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
malfunction
-
sphingomyelin synthase (SMS) deficiency promotes cell migration through a CXCL12/CXCR4-dependent signaling pathway involving extracellular signal-regulated kinase activation. In addition, SMS1/SMS2 double-knockout cells have heightened sensitivity to CXCL12. SMS deficiency facilitates relocalization of CXCR4 to lipid rafts, which form platforms for the regulation and transduction of receptor-mediated signaling. Furthermore, SMS deficiency potentiates CXCR4 dimerization, which is required for signal transduction
malfunction
glucose kinetics study using the radiolabeled glucose analog 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG), in wild-type (WT) and SMS2 knockout (KO) mice: insulin signaling is enhanced in the liver, white adipose tissue and skeletal muscle of SMS2 KO mice compared with those of wild-type mice. In addition, compared with in wild-type mice, blood clearance of 18F-FDG is accelerated in SMS2 KO mice when they are fed either a normal or a high fat diet. 18F-FDG uptake is also increased in insulin-targeted tissues such as skeletal muscle in the SMS2 KO mice, whereas skeletal muscle sphingolipid content is not clearly affected. Plasma levels of very long-chain fatty acid (VLCFA)-containing ceramides are markedly increased in SMS2 KO mice compared with in wild-type mice. Genetic inhibition of SMS2 elevates glucose clearance through activation of glucose uptake into insulin-targeted tissues such as skeletal muscle by a mechanism independent of hepatic SMS2. This occurs, at least in part, via indirect mechanisms such as elevation of VLCFA-containing ceramides
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
malfunction
-
glucose kinetics study using the radiolabeled glucose analog 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG), in wild-type (WT) and SMS2 knockout (KO) mice: insulin signaling is enhanced in the liver, white adipose tissue and skeletal muscle of SMS2 KO mice compared with those of wild-type mice. In addition, compared with in wild-type mice, blood clearance of 18F-FDG is accelerated in SMS2 KO mice when they are fed either a normal or a high fat diet. 18F-FDG uptake is also increased in insulin-targeted tissues such as skeletal muscle in the SMS2 KO mice, whereas skeletal muscle sphingolipid content is not clearly affected. Plasma levels of very long-chain fatty acid (VLCFA)-containing ceramides are markedly increased in SMS2 KO mice compared with in wild-type mice. Genetic inhibition of SMS2 elevates glucose clearance through activation of glucose uptake into insulin-targeted tissues such as skeletal muscle by a mechanism independent of hepatic SMS2. This occurs, at least in part, via indirect mechanisms such as elevation of VLCFA-containing ceramides
-
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 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
-
isoform SMS2, rather than isoform SMS1, is the major enzyme that is important for sphingomyelin synthesis in the long neurites and the growth cone
physiological function
-
sphingomyelin synthase-generated sphingomyelin is involed in the regulation of cell migration
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
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
physiological function
role of sphingomyelin synthase 2 in glucose metabolism in whole-body and peripheral tissues in mice
physiological function
sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin. Effect of SMS on the inflammatory pathway involving nuclear factor (NF)kappaB induced by lipopolysaccharide is analyzed in an ALI mouse model, overview. Compared with the control group, the mRNA and protein levels of CD14 are significantly increased, and the activity of SMS and expression of SMS2 are significantly upregulated in the model group. The expression of SMS2 may affect the induction of the NFkappaB pathway by LPS through CD14
physiological function
in SMS2 knockout mice, SMS2 deficiency significantly decreases very long chain sphingomyelin (d18:1/22:0 and d18:1/24:0 or d18:0/24:1) and increases very long chain ceramie (d18:1/24:0 or d18:0/24:1 and d18:1/24:1), but not long chain sphingomyelin (d18:1/16:0, d18:1/18:0 or d18:0/18:1 and d18:1/18:1) in plasma. Presence of sphingomyelin d18:1/24:0 strongly upregulated several macrophage activation markers, sphingomyelin d18:1/6:0 and ceramide d18:1/24:0 however, does not
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
physiological function
Sms1-/- mice show a spermatogenesis defect, characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. A reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids is observed in the testes of mutants, together with blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminishes germ cell sloughing from the seminiferous epithelium and restores spermatogenesis and fertility in 50% of previously infertile mutants
physiological function
-
sphingomyelins are abundant in Nilaparvata lugens and synthesized by sphingomyelin synthase-like protein SMSL2. Contrary to other insects, high concentrations of sphingomyelins rather than ceramide phosphoethanolamines exist in Nilaparvata lugens. Knockdowns of isoform SMSL2 decrease concentrations of sphingomyelins. The knockdown of SMSL1 or SMSL2 increases female body weight but not that of males
physiological function
treatment with bacterial lipopolysaccharide up-regulates the expression and activity of sphingomyelin synthases while exposure to inhibitor tricyclodecane-9-yl xanthogenate or silencing of isoforms SGMS1 and SGMS2 counteract this action. SGMS1 silencing leads to a depletion of sphingomyelin in cells. Concomitantly, the MyD88- and TRIF-dependent signaling pathways of TLR4 are inhibited with the latter being especially sensitive to the reduction of the SGMS1 and/or SGMS2 activity. The tricyclodecane-9-yl xanthogenate treatment and SMS1 and/or SMS2 depletion all reduce the level of CD14 protein in cells
physiological function
-
role of sphingomyelin synthase 2 in glucose metabolism in whole-body and peripheral tissues in mice
-
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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). SLS3_TRYBB
329
5
37084
Swiss-Prot
Mitochondrion (Reliability: 4)
SLS4_TRYB2
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
365
5
40857
Swiss-Prot
Secretory Pathway (Reliability: 5)
SLS4_TRYBB
365
5
40900
Swiss-Prot
Secretory Pathway (Reliability: 5)
SLS3_TRYB2
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
329
5
37180
Swiss-Prot
Mitochondrion (Reliability: 4)
SMS1_CAEEL
469
6
52642
Swiss-Prot
other Location (Reliability: 1)
SMS1_CHICK
417
6
49014
Swiss-Prot
other Location (Reliability: 2)
SMS1_HUMAN
413
6
48617
Swiss-Prot
other Location (Reliability: 2)
SMS1_MOUSE
419
6
49317
Swiss-Prot
other Location (Reliability: 2)
SMS1_PIG
418
6
48984
Swiss-Prot
other Location (Reliability: 2)
SMS1_RAT
419
6
49014
Swiss-Prot
other Location (Reliability: 2)
SMS2_CAEEL
335
6
38737
Swiss-Prot
other Location (Reliability: 2)
SMS2_HUMAN
365
6
42280
Swiss-Prot
other Location (Reliability: 1)
SMS2_MACFA
365
6
42352
Swiss-Prot
other Location (Reliability: 1)
SMS2_MOUSE
365
6
42248
Swiss-Prot
other Location (Reliability: 1)
SMS2_RAT
365
6
42223
Swiss-Prot
other Location (Reliability: 1)
SMS3_CAEEL
340
4
38185
Swiss-Prot
other Location (Reliability: 3)
A4HNG1_LEIBR
385
5
43189
TrEMBL
other Location (Reliability: 4)
A0A0B2QS84_GLYSO
229
2
26003
TrEMBL
Secretory Pathway (Reliability: 4)
C6KT87_PLAF7
399
6
46660
TrEMBL
other Location (Reliability: 2)
A0A653HP82_9APIC
467
6
55055
TrEMBL
other Location (Reliability: 1)
A0A0Y9XUN5_PLABE
389
6
45280
TrEMBL
other Location (Reliability: 2)
A0A1C6YK44_PLACH
400
6
45921
TrEMBL
other Location (Reliability: 2)
A0A1D3TJB1_9APIC
414
6
47815
TrEMBL
other Location (Reliability: 1)
A0A7R8H0K6_LEPSM
605
6
69735
TrEMBL
other Location (Reliability: 1)
A0A060RV24_PLARE
439
6
51995
TrEMBL
other Location (Reliability: 1)
Q28DN3_XENTR
365
6
42231
TrEMBL
other Location (Reliability: 1)
A0A653H6W6_9APIC
470
4
55198
TrEMBL
other Location (Reliability: 1)
A0A3R7MTS5_9TRYP
332
4
37140
TrEMBL
Secretory Pathway (Reliability: 2)
A0A1C3KU41_9APIC
478
6
56052
TrEMBL
other Location (Reliability: 4)
A0A1J1HBE6_PLARL
430
6
50488
TrEMBL
other Location (Reliability: 2)
A0A1C6YGL4_PLACH
394
6
46081
TrEMBL
other Location (Reliability: 2)
A0A5B6ZQJ3_DAVIN
292
3
33564
TrEMBL
other Location (Reliability: 4)
A0A061IQB3_CRIGR
374
6
43042
TrEMBL
other Location (Reliability: 1)
A0A3S7XA07_LEIDO
385
5
42645
TrEMBL
other Location (Reliability: 4)
A0A1C3KZH9_PLAMA
237
3
27923
TrEMBL
other Location (Reliability: 3)
Q6NTY1_XENLA
412
4
48152
TrEMBL
other Location (Reliability: 2)
A0A2T6IYT6_TOXGO
292
4
31997
TrEMBL
Mitochondrion (Reliability: 5)
A0A061IAB5_CRIGR
466
6
54456
TrEMBL
Mitochondrion (Reliability: 2)
A0A5B6ZQS6_DAVIN
311
3
35616
TrEMBL
other Location (Reliability: 4)
A0A077TQR3_PLACH
394
6
45957
TrEMBL
other Location (Reliability: 2)
A0A077Y675_PLAYE
395
6
45998
TrEMBL
other Location (Reliability: 2)
A0A5B6ZMV2_DAVIN
312
3
35679
TrEMBL
other Location (Reliability: 4)
A0A1C6YGR1_PLACH
400
6
45976
TrEMBL
other Location (Reliability: 2)
A0A060RVB7_PLARE
399
6
46720
TrEMBL
other Location (Reliability: 2)
G3I338_CRIGR
365
6
42077
TrEMBL
other Location (Reliability: 1)
A0A5K1TZ57_PLAKH
472
4
54556
TrEMBL
other Location (Reliability: 1)
A0A384LQJ1_PLAKH
472
4
54556
TrEMBL
other Location (Reliability: 1)
A0A143ZVB5_PLAF7
439
6
51828
TrEMBL
other Location (Reliability: 1)
A0A1D3RYC8_PLACH
394
6
45921
TrEMBL
other Location (Reliability: 2)
A4IC70_LEIIN
385
5
42701
TrEMBL
other Location (Reliability: 4)
A0JMN0_DANRE
404
6
46988
TrEMBL
other Location (Reliability: 1)
A0A5K1TW26_PLAKH
401
6
46366
TrEMBL
other Location (Reliability: 2)
A0A088S1L7_9TRYP
385
5
43285
TrEMBL
other Location (Reliability: 4)
A0A0B2RGX9_GLYSO
314
3
35698
TrEMBL
other Location (Reliability: 4)
A0A1D3TJB5_9APIC
478
6
56330
TrEMBL
other Location (Reliability: 3)
A0A1C3KU76_9APIC
414
6
47768
TrEMBL
other Location (Reliability: 1)
A0A7R8H3C6_LEPSM
540
6
61291
TrEMBL
other Location (Reliability: 4)
A0A1D3SP04_PLAMA
461
4
53737
TrEMBL
other Location (Reliability: 4)
Q640R5_XENTR
412
4
48085
TrEMBL
other Location (Reliability: 1)
A0A384K820_PLAKH
401
6
46366
TrEMBL
other Location (Reliability: 2)
A0A1J1H7G1_PLARL
399
6
46683
TrEMBL
other Location (Reliability: 1)
A0A8M1NT99_DANRE
351
6
40237
TrEMBL
other Location (Reliability: 1)
A0A0Y9XUM9_PLABE
401
6
46656
TrEMBL
other Location (Reliability: 1)
A0A1D3RY74_PLACH
394
6
45945
TrEMBL
other Location (Reliability: 2)
A0A1D3RYA0_PLACH
400
6
45852
TrEMBL
other Location (Reliability: 2)
A0A422NCN9_TRYRA
331
5
37218
TrEMBL
Secretory Pathway (Reliability: 3)
A0A1D3RYA1_PLACH
400
6
45993
TrEMBL
other Location (Reliability: 2)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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
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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
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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
-
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 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
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%
additional information
-
S49AR cells show a defect in the synthesis of sphingomyelin and downregulated SMS1, phenotype, overview. Resistance to ALP can be mimicked by small interfering RNA-induced SMS1 suppression, resulting in sphingomyelin deficiency and blockage of raft-dependent internalization of ALP and induction of apoptosis, overview
additional information
-
sphingomyelin synthase 2 knockout deficiency attenuates NFkappaB activation, it impairs TNF receptor 1 recruitment tolipid rafts and TLR4-MD2 complex recruitment to plasma membrane
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
adenovirus approach to overexpress SMS1 in mice to investigate the relationship between sphingomyelin synthase and sphingomyelin metabolism
adenovirus approach to overexpress SMS2 in mice to investigate the relationship between sphingomyelin synthase and sphingomyelin metabolism
expressed in HeLa cells
expression analysis of isozymes SMS1 and SMS2 by RT-PCR, recombinant overexpression of isozymes SMS1 and SMS2 in HeLa cells
-
expression in FreeStyle293 cells
gene SMS1, DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis, quantitative expression analysis by real-time RT-PCR
gene SMS1, expression analysis in healthy and ischemic neurons, effect of permanent middle cerebral artery occlusion on expression of SMS1 transcripts, overview
-
gene SMS2 from testis, DNA and amino acid sequence determination and analysis, sequence comparison, tissue expression analysis, overview
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
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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
-
lipopolysaccharide induction analyzed in an ALI mouse model, compared with the control group, the mRNA and protein levels of CD14 are significantly increased, and the activity of SMS and expression of SMS2 are significantly upregulated in the model group
treatment with bacterial lipopolysaccharide up-regulates the expression and activity of sphingomyelin synthases
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
pharmacology
drug development
enzyme SMS1 is a drug target for the treatment of atherosclerosis
medicine
adenovirus-mediated SMS1 overexpression increases lipoprotein atherogenic potential. Such an effect may contribute to the increased plasma sphingomyelin levels observed in animal models of atherosclerosis and in human patients with coronary artery disease
medicine
adenovirus-mediated SMS2 overexpression increases lipoprotein atherogenic potential. Such an effect may contribute to the increased plasma sphingomyelin levels observed in animal models of atherosclerosis and in human patients with coronary artery disease
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
medicine
-
regulation of liver SMS2 may be used as treatment for atherosclerosis
medicine
-
SMS2 is a potential therapeutic target for treatment of atherosclerosis
medicine
SMS inhibitors might be useful for the treatment of atherosclerosis or coronary artery disease
pharmacology
sphingomyelin synthase 2 (SMS2) is a potential therapeutic target for obesity and insulin resistance
pharmacology
-
sphingomyelin synthase 2 (SMS2) is a potential therapeutic target for obesity and insulin resistance
-
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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
brenda
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
brenda
Hanada, K.; Horii, M.; Akamatsu, Y.
Functional reconstitution of sphingomyelin synthase in Chinese hamster ovary cell membranes
Biochim. Biophys. Acta
1086
151-156
1991
Cricetulus griseus
brenda
Allan, D.; Obradors, M.J.
Enzyme distributions in subcellular fractions of BHK cells infected with Semliki forest virus: evidence for a major fraction of sphingomyelin synthase in the trans-Golgi network
Biochim. Biophys. Acta
1450
277-287
1999
Mesocricetus auratus
brenda
Miro-Obradors, M.J.; Osada, J.; Aylagas, H.; Sanchez-Vegazo, I.; Palacios-Alaiz, E.
Microsomal sphingomyelin accumulation in thioacetamide-injured regenerating rat liver: involvement of sphingomyelin synthase activity
Carcinogenesis
14
941-946
1993
Rattus norvegicus
brenda
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
brenda
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
brenda
Albi, E.; Magni, M.V.
Sphingomyelin synthase in rat liver nuclear membrane and chromatin
FEBS Lett.
460
369-372
1999
Rattus norvegicus
brenda
Albi, E.; Lazzarini, R.; Magni, M.V.
Reverse sphingomyelin-synthase in rat liver chromatin
FEBS Lett.
549
152-156
2003
Rattus norvegicus
brenda
Yang, Z.; Khoury, C.; Jean-Baptiste, G.; Greenwood, M.T.
Identification of mouse sphingomyelin synthase 1 as a suppressor of Bax-mediated cell death in yeast
FEMS Yeast Res.
6
751-762
2006
Mus musculus (Q8VCQ6), Mus musculus
brenda
Guillen, N.; Navarro, M.A.; Surra, J.C.; Arnal, C.; Fernandez-Juan, M.; Cebrian-Perez, J.A.; Osada, J.
Cloning, characterization, expression and comparative analysis of pig Golgi membrane sphingomyelin synthase 1
Gene
388
117-124
2007
Sus scrofa (A0AAS4), Sus scrofa
brenda
van Helvoort, A.; van't Hof, W.; Ritsema, T.; Sandra, A.; van Meer, G.
Conversion of diacylglycerol to phosphatidylcholine on the basolateral surface of epithelial (Madin-Darby canine kidney) cells. Evidence for the reverse action of a sphingomyelin synthase
J. Biol. Chem.
269
1763-1769
1994
Canis lupus familiaris
brenda
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
brenda
Luberto, C.; Stonehouse, M.J.; Collins, E.A.; Marchesini, N.; El-Bawab, S.; Vasil, A.I.; Vasil, M.L.; Hannun, Y.A.
Purification, characterization, and identification of a sphingomyelin synthase from Pseudomonas aeruginosa. PlcH is a multifunctional enzyme
J. Biol. Chem.
278
32733-32743
2003
Pseudomonas aeruginosa
brenda
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
brenda
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)
brenda
Elmendorf, H.G.; Haldar, K.
Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubovesicular network in the cytoplasm of mature erythrocytes
J. Cell Biol.
124
449-462
1994
Plasmodium falciparum
brenda
Lee, N.P.; Mruk, D.D.; Xia, W.; Cheng, C.Y.
Cellular localization of sphingomyelin synthase 2 in the seminiferous epithelium of adult rat testes
J. Endocrinol.
192
17-32
2007
Rattus norvegicus, Rattus norvegicus (Q4JM44)
brenda
Dong, J.; Liu, J.; Lou, B.; Li, Z.; Ye, X.; Wu, M.; Jiang, X.C.
Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice
J. Lipid Res.
47
1307-1314
2006
Mus musculus (Q8VCQ6), Mus musculus (Q9D4B1), Mus musculus
brenda
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
brenda
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
brenda
Van der luit, A.H.; Budde, M.; Zerp, S.; Caan, W.; Klarenbeek, J.B.; Verheij, M.; van Blitterswijk, W.J.
Resistance to alkyl-lysophospholipid-induced apoptosis due to downregulated sphingomyelin synthase 1 expression with consequent sphingomyelin- and cholesterol-deficiency in lipid rafts
Biochem. J.
401
541-549
2007
Mus musculus
brenda
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
brenda
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
brenda
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)
brenda
Dmitrieva, V.G.; Torshina, E.V.; Yuzhakov, V.V.; Povarova, O.V.; Skvortsova, V.I.; Limborska, S.A.; Dergunova, L.V.
Expression of sphingomyelin synthase 1 gene in rat brain focal ischemia
Brain Res.
1188
222-227
2008
Rattus norvegicus
brenda
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
brenda
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
brenda
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
brenda
Liu, J.; Zhang, H.; Li, Z.; Hailemariam, T.K.; Chakraborty, M.; Jiang, K.; Qiu, D.; Bui, H.H.; Peake, D.A.; Kuo, M.S.; Wadgaonkar, R.; Cao, G.; Jiang, X.C.
Sphingomyelin synthase 2 is one of the determinants for plasma and liver sphingomyelin levels in mice
Arterioscler. Thromb. Vasc. Biol.
29
850-856
2009
Mus musculus
brenda
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
brenda
Liu, J.; Huan, C.; Chakraborty, M.; Zhang, H.; Lu, D.; Kuo, M.S.; Cao, G.; Jiang, X.C.
Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice
Circ. Res.
105
295-303
2009
Mus musculus
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Kidani, Y.; Ohshima, K.; Sakai, H.; Kohno, T.; Baba, A.; Hattori, M.
Differential localization of sphingomyelin synthase isoforms in neurons regulates sphingomyelin cluster formation
Biochem. Biophys. Res. Commun.
417
1014-1017
2012
Mus musculus
brenda
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
brenda
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
brenda
Man, C.; Lee, J.
Molecular cloning, sequence characterization, and tissue expression analysis of chicken sphingomyelin synthase 1 (SMS1)
Mol. Cell. Biochem.
357
353-361
2011
Gallus gallus (Q7T3T4), Gallus gallus
brenda
Asano, S.; Kitatani, K.; Taniguchi, M.; Hashimoto, M.; Zama, K.; Mitsutake, S.; Igarashi, Y.; Takeya, H.; Kigawa, J.; Hayashi, A.; Umehara, H.; Okazaki, T.
Regulation of cell migration by sphingomyelin synthases: sphingomyelin in lipid rafts decreases responsiveness to signaling by the CXCL12/CXCR4 pathway
Mol. Cell. Biol.
32
3242-3252
2012
Mus musculus
brenda
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)
brenda
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
brenda
Subathra, M.; Qureshi, A.; Luberto, C.
Sphingomyelin synthases regulate protein trafficking and secretion
PLoS ONE
6
e23644
2011
Homo sapiens, Rattus norvegicus
brenda
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
brenda
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
brenda
Sugimoto, M.; Shimizu, Y.; Zhao, S.; Ukon, N.; Nishijima, K.; Wakabayashi, M.; Yoshioka, T.; Higashino, K.; Numata, Y.; Okuda, T.; Tamaki, N.; Hanamatsu, H.; Igarashi, Y.; Kuge, Y.
Characterization of the role of sphingomyelin synthase 2 in glucose metabolism in whole-body and peripheral tissues in mice
Biochim. Biophys. Acta
1861
688-702
2016
Mus musculus (Q9D4B1), Mus musculus C57BL/6N (Q9D4B1)
brenda
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)
brenda
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)
-
brenda
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)
brenda
Huang, T.; Li, X.; Hu, S.; Zhao, B.; Chen, P.; Liu, X.; Ye, D.; Cheng, N.
Analysis of fluorescent ceramide and sphingomyelin analogs: a novel approach for in vivo monitoring of sphingomyelin synthase activity
Lipids
49
1071-1079
2014
Mus musculus (Q9D4B1)
brenda
Hu, S.; Ding, Y.; Gong, J.; Yan, N.
Sphingomyelin synthase 2 affects CD14-associated induction of NF kappaB by lipopolysaccharides in acute lung injury in mice
Mol. Med. Rep.
14
3301-3306
2016
Mus musculus (Q9D4B1), Mus musculus
brenda
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
brenda
Deng, X.; Sun, H.; Gao, X.; Gong, H.; Lu, W.; Chu, Y.; Zhou, L.; Ye., D.
Development, validation, and application of a novel method for mammalian sphingomyelin synthase activity measurement
Anal. Lett.
45
1581-1589
2012
Mus musculus
-
brenda
Sakamoto, H.; Yoshida, T.; Sanaki, T.; Shigaki, S.; Morita, H.; Oyama, M.; Mitsui, M.; Tanaka, Y.; Nakano, T.; Mitsutake, S.; Igarashi, Y.; Takemoto, H.
Possible roles of long-chain sphingomyelines and sphingomyelin synthase 2 in mouse macrophage inflammatory response
Biochem. Biophys. Res. Commun.
482
202-207
2017
Mus musculus (Q9D4B1), Mus musculus
brenda
Prymas, K.; Swiatkowska, A.; Traczyk, G.; Ziemlinska, E.; Dziewulska, A.; Ciesielska, A.; Kwiatkowska, K.
Sphingomyelin synthase activity affects TRIF-dependent signaling of Toll-like receptor 4 in cells stimulated with lipopolysaccharide
Biochim. Biophys. Acta
1865
158549
2020
Mus musculus (Q8VCQ6), Mus musculus (Q9D4B1)
brenda
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)
brenda
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
brenda
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)
brenda
Shi, X.; Zhang, H.; Chen, M.; Zhang, Y.; Zhu, M.; Zhang, M.; Li, F.; Wratten, S.; Zhou, W.; Mao, C.; Zhu, Z.
Two sphingomyelin synthase homologues regulate body weight and sphingomyelin synthesis in female brown planthopper, N.xa0lugens (Stal)
Insect Mol. Biol.
28
253-263
2019
Nilaparvata lugens
brenda
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)
brenda
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)
-
brenda
Li, X.; Luo, T.; Li, H.; Yan, N.
Sphingomyelin synthase 2 participate in the regulation of sperm motility and apoptosis
Molecules
25
4231
2020
Homo sapiens (Q8NHU3), Homo sapiens
brenda
Wittmann, A.; Grimm, M.O.; Scherthan, H.; Horsch, M.; Beckers, J.; Fuchs, H.; Gailus-Durner, V.; Hrabe de Angelis, M.; Ford, S.J.; Burton, N.C.; Razansky, D.; Truembach, D.; Aichler, M.; Walch, A.K.; Calzada-Wack, J.; Neff, F.; Wurst, W.; Hartmann, T.; Floss, T.
Sphingomyelin synthase 1 is essential for male fertility in mice
PLoS ONE
11
e0164298
2016
Mus musculus (Q8VCQ6), Mus musculus
brenda
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