Information on EC 2.7.8.27 - sphingomyelin synthase

for references in articles please use BRENDA:EC2.7.8.27
Word Map on EC 2.7.8.27
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:


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

EC NUMBER
COMMENTARY hide
2.7.8.27
-
RECOMMENDED NAME
GeneOntology No.
sphingomyelin synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
substituted phospho group transfer
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
sphingolipid biosynthesis (mammals)
-
-
sphingomyelin metabolism
-
-
Sphingolipid metabolism
-
-
Metabolic pathways
-
-
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 hide
58703-97-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
breed Hi-Line Brown
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
; SMS1
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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
show the reaction diagram
-
-
-
?
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
show the reaction diagram
ceramide + phosphatidylcholine
sphingomyelin + 1,2-diacyl-sn-glycerol
show the reaction diagram
L-alpha-phosphatidylcholine + N-(6-[(7-nitro-benz-2-oxa-1,3-diazo-4-yl)amino]caproyl)-ceramide
?
show the reaction diagram
-
i.e. NBD-C6-ceramide
-
-
?
L-alpha-phosphatidylcholine + NBD-C6-ceramide
?
show the reaction diagram
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
show the reaction diagram
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
?
show the reaction diagram
-
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
show the reaction diagram
-
-
-
-
ir
phosphatidylcholine + C6-ceramide
?
show the reaction diagram
-
-
-
-
?
phosphatidylcholine + C6-ceramide
C6-sphingomyelin + 1,2-diacyl-sn-glycerol
show the reaction diagram
phosphatidylcholine + C6-NBD-ceramide
?
show the reaction diagram
-
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
show the reaction diagram
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
show the reaction diagram
phosphatidylcholine + ceramide
sphingomyelin + diacylglycerol
show the reaction diagram
sphingomyelin + diacylglycerol
ceramide + phosphatidylcholine
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
a ceramide + a phosphatidylcholine
a sphingomyelin + a 1,2-diacyl-sn-glycerol
show the reaction diagram
ceramide + phosphatidylcholine
sphingomyelin + 1,2-diacyl-sn-glycerol
show the reaction diagram
phosphatidylcholine + ceramide
sphingomyelin + 1,2-diacyl-sn-glycerol
show the reaction diagram
Q86VZ5, Q8NHU3
-
-
-
?
phosphatidylcholine + ceramide
sphingomyelin + diacylglycerol
show the reaction diagram
Q4JM44
SMS2 is crucial to cellular lipid metabolism
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
-
Mn2+
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(2-(benzyloxy)phenyl)-2-(phenylamino) acetonitrile
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(2-(trifluoromethoxy)phenyl)acetamide
-
-
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(o-tolyl)acetamide
-
-
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-phenylacetamide
-
-
4-(2-((4-chlorobenzyl)amino)-2-oxoethoxy)-N-(pyridin-4-yl)benzamide
-
-
4-(2-((4-chlorobenzyl)amino)-2-oxoethoxy)-N-phenethylbenzamide
-
-
ceramide
-
-
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
-
Mn2+
-
4 mM, about 40% inhibition
N-(2-cyanophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(2-nitrophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(3-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(3-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-bromobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-chlorobenzyl)-2-(4-(N-(3-phenylpropyl)sulfamoyl)phenoxy)acetamide
-
-
N-(4-chlorobenzyl)-2-(4-(N-(4-chlorobenzyl)sulfamoyl)phenoxy)acetamide
-
-
N-(4-chlorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-chlorobenzyl)-2-(4-(N-phenylsulfamoyl)phenoxy)acetamide
-
-
N-(4-chlorophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-fluoro-2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-fluorophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-methoxybenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-(4-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-benzyl-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
N-phenethyl-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
-
-
Ni2+
-
2 mM, 75% inhibition
potassium tricyclodecan-9-yl-xanthogenate
-
i.e. D609, decreases enzyme activity an sphingomyelin levels in different human cell lines in vivo
sphingosine
-
-
tricyclodecan-9-yl-xanthogenate
-
tumor necrosis factor-alpha
-
-
-
Zn2+
-
0.5 mM, about 95% inhibition
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.006277 - 0.007235
C6-ceramide
0.00538 - 0.005549
C8-ceramide
0.112
diacylglycerol
-
-
0.0356
sphingomyelin
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0135 - 0.025
2-(2-(benzyloxy)phenyl)-2-(phenylamino) acetonitrile
0.1
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(2-(trifluoromethoxy)phenyl)acetamide
Homo sapiens
-
pH 7.4, 37C
0.1
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-(o-tolyl)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0147
2-(4-(N-phenethylsulfamoyl)phenoxy)-N-phenylacetamide
Homo sapiens
-
pH 7.4, 37C
0.1
4-(2-((4-chlorobenzyl)amino)-2-oxoethoxy)-N-(pyridin-4-yl)benzamide
Homo sapiens
-
pH 7.4, 37C
0.1
4-(2-((4-chlorobenzyl)amino)-2-oxoethoxy)-N-phenethylbenzamide
Homo sapiens
-
pH 7.4, 37C
0.622 - 1.065
D609
0.1
N-(2-cyanophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0142
N-(2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.1
N-(2-nitrophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0156
N-(3-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0092
N-(3-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0021
N-(4-bromobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.1
N-(4-chlorobenzyl)-2-(4-(N-(3-phenylpropyl)sulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.05
N-(4-chlorobenzyl)-2-(4-(N-(4-chlorobenzyl)sulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0052
N-(4-chlorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.1
N-(4-chlorobenzyl)-2-(4-(N-phenylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0066
N-(4-chlorophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.1
N-(4-fluoro-2-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0081
N-(4-fluorobenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0105
N-(4-fluorophenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0059
N-(4-methoxybenzyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.05
N-(4-methoxyphenyl)-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.0231
N-benzyl-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.05
N-phenethyl-2-(4-(N-phenethylsulfamoyl)phenoxy)acetamide
Homo sapiens
-
pH 7.4, 37C
0.219 - 0.4027
tricyclodecan-9-yl-xanthogenate
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9.5
-
pH 7: about 50% of maximal activity, pH 9.5: 65% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
; high expression of SMS1 mRNA
Manually annotated by BRENDA team
-
infected with Semliki forest virus
Manually annotated by BRENDA team
-
isozymes SMS1 and SMS2
Manually annotated by BRENDA team
; high expression of SMS1 mRNA
Manually annotated by BRENDA team
; moderate expression of SMS1 mRNA
Manually annotated by BRENDA team
low SMS1 expression level; weak expression of SMS1 mRNA
Manually annotated by BRENDA team
; moderate expression of SMS1 mRNA
Manually annotated by BRENDA team
-
isozymes SMS1 and SMS2
Manually annotated by BRENDA team
primary culture
Manually annotated by BRENDA team
-
a hepatoma cell line
Manually annotated by BRENDA team
; high expression of SMS1 mRNA
Manually annotated by BRENDA team
; weak expression of SMS1 mRNA
Manually annotated by BRENDA team
-
basolateral cell surface
Manually annotated by BRENDA team
-
isozymes SMS1 and SMS2
Manually annotated by BRENDA team
; weak expression of SMS1 mRNA
Manually annotated by BRENDA team
-
isozymes SMS1 and SMS2
Manually annotated by BRENDA team
-
the enzyme is localized within the plasma mebrane
Manually annotated by BRENDA team
-
isozymes SMS1 and SMS2
Manually annotated by BRENDA team
-
exports a substantial fraction of sphingomyelin synthase activity to membranes beyond their plasma membrane
Manually annotated by BRENDA team
-
lymphoma cell line, expression of SMS1, not of SMS2
Manually annotated by BRENDA team
primary culture
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
; high expression of SMS1 mRNA
Manually annotated by BRENDA team
; seminiferous epithelium of adult rat
Manually annotated by BRENDA team
-
exports a substantial fraction of sphingomyelin synthase activity to membranes beyond their plasma membrane
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
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
-
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
a small portion of SMS2 is found in the perinuclear region
-
Manually annotated by BRENDA team
-
Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubovesicular network in the cytoplasm of mature erythrocytes
-
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
48540
x * 48540, calculated from amino acid sequence
54000
x * 54000, SDS-PAGE; x * 54000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
side-chain modification
-
SMS2 is palmitoylated at cysteine residues via thioester bonds in the COOH-terminal cytoplasmic tail, SMS1 is not palmitoylated
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; gene SMS1, DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis, quantitative expression analysis by real-time RT-PCR
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 Chinese hamster ovary cells
-
expressed in Escherichia coli DH5alpha cells
expressed in HeLa cells
expressed in in Sf9 insect cells; expressed in in Sf9 insect cells
expressed in Mus musculus (ApoE knockout mice)
-
expression analysis of isozymes SMS1 and SMS2 by RT-PCR
-
expression analysis of isozymes SMS1 and SMS2 by RT-PCR, recombinant overexpression of isozymes SMS1 and SMS2 in HeLa cells
-
expression in mouse lymphoid cell line
-
expression in yeast cells
-
gene SGMS1, recombinnat overexpression of isozyme SMS1 in HeLa cells
-
gene Sgms2, relative real-time PCR expression analysis
-
gene SMS1
-
gene SMS1, expression analysis in healthy and ischemic neurons, effect of permanent middle cerebral artery occlusion on expression of SMS1 transcripts, overview
-
gene SMS1, expression in Jurkat cells, expression levels, overview
-
gene SMS2 from testis, DNA and amino acid sequence determination and analysis, sequence comparison, tissue expression analysis, overview; SMS2
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
-
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
pharmacology