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Information on EC 2.3.1.297 - very-long-chain ceramide synthase and Organism(s) Mus musculus and UniProt Accession Q924Z4
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2.3.1.297 very-long-chain ceramide synthaseIUBMB Comments
This entry describes ceramide synthase enzymes that are specific for very-long-chain fatty acyl-CoA substrates. The two isoforms from yeast and the plant LOH1 and LOH3 isoforms transfer 24:0 and 26:0 acyl chains preferentially and use phytosphingosine as the preferred sphingoid base. The mammalian CERS2 isoform is specific for acyl donors of 20-26 carbons, which can be saturated or unsaturated. The mammalian CERS3 isoform catalyses this activity, but has a broader substrate range and also catalyses the activity of EC 2.3.1.298, ultra-long-chain ceramide synthase. Both mammalian enzymes can use multiple sphingoid bases, including sphinganine, sphingosine, and phytosphingosine.
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Word Map
- 2.3.1.297
- sphingolipids
- sphingomyelins
- dihydroceramide
-
cers1-6
- elovl1
- pnpla1
- cyp4f22
- alox12b
-
sdr9c7
-
nipal4
-
abca12
-
cerss
- aloxe3
- diagnostics
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
a very-long-chain fatty acyl-CoA
+
=
a very-long-chain ceramide
+
Synonyms
cers2, lass2, cers3, ceramide synthase 2, ceramide synthase 3, lass4, lass3, longevity assurance homologue 2, lag13, lag11, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CerS3
LAC1
-
-
-
-
LAG1
-
-
-
-
LASS3
LOH1
-
-
-
-
LOH3
-
-
-
-
mammalian ceramide synthase 2
-
-
-
-
sphingoid base N-very-long-chain fatty acyl-coA transferase
-
-
-
-
CerS3
-
-
-
-
LASS3
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
very-long-chain fatty acyl-coA:sphingoid base N-acyltransferase
This entry describes ceramide synthase enzymes that are specific for very-long-chain fatty acyl-CoA substrates. The two isoforms from yeast and the plant LOH1 and LOH3 isoforms transfer 24:0 and 26:0 acyl chains preferentially and use phytosphingosine as the preferred sphingoid base. The mammalian CERS2 isoform is specific for acyl donors of 20-26 carbons, which can be saturated or unsaturated. The mammalian CERS3 isoform catalyses this activity, but has a broader substrate range and also catalyses the activity of EC 2.3.1.298, ultra-long-chain ceramide synthase. Both mammalian enzymes can use multiple sphingoid bases, including sphinganine, sphingosine, and phytosphingosine.
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
D-erythro-sphinganine + arachidoyl-CoA
N-arachidoyl-D-sphinganine + CoA
-
-
-
?
D-erythro-sphinganine + cerotoyl-CoA
N-cerotoyl-D-sphinganine + CoA
-
-
-
?
nervonoyl-CoA + NBD-sphinganine
CoA + N-nervonoyl-NBD-sphinganine
C24:1-CoA substrate and NBD-labeled sphinganine substrate, i.e. omega(7-nitro-2-1,3-benzoxadiazole-4-yl)(2S,3R)-2-aminooctadecane-1,3-diol
-
-
?
sphinganine + cerotoyl-CoA
N-cerotoylsphinganine + CoA
low activity
-
-
?
sphingosine + arachidoyl-CoA
N-arachidoylsphingosine + CoA
low activity
-
-
?
sphingosine + hexacosanoyl-CoA
N-hexacosanoylsphingosine + CoA
low activity
-
-
?
sphingosine + lignoceroyl-CoA
N-lignoceroylsphingosine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
low activity
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
-
-
-
-
?
sphingosine + arachidoyl-CoA
N-arachidoylsphingosine + CoA
low activity
-
-
?
sphingosine + hexacosanoyl-CoA
N-hexacosanoylsphingosine + CoA
low activity
-
-
?
sphingosine + lignoceroyl-CoA
N-lignoceroylsphingosine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
low activity
-
-
?
D-erythro-sphinganine + behenoyl-CoA
N-behenoyl-D-sphinganine + CoA
-
-
-
?
D-erythro-sphinganine + behenoyl-CoA
N-behenoyl-D-sphinganine + CoA
preferred substrate
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
-
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
-
-
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
preferred substrate
-
-
?
D-erythro-sphinganine + nervonoyl-CoA
N-nervonoyl-D-sphinganine + CoA
-
-
-
?
a very-long-chain fatty acyl-CoA + a sphingoid base
a very-long-chain ceramide + CoA
-
-
-
-
?
a very-long-chain fatty acyl-CoA + a sphingoid base
a very-long-chain ceramide + CoA
-
the enzyme synthesizes ceramides with very-long (C22-C24) acyl chains
-
-
?
sphinganine + arachidoyl-CoA
N-arachidoylsphinganine + CoA
low activity
-
-
?
sphinganine + behenoyl-CoA
N-behenoylsphinganine + CoA
moderate activity
-
-
?
sphinganine + cerotoyl-CoA
N-cerotoylsphinganine + CoA
low activity
-
-
?
sphinganine + lignoceroyl-CoA
N-lignoceroylsphinganine + CoA
high activity
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
low activity
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
preferred substrate
-
-
?
additional information
?
-
ceramide synthase 2 catalyzes the synthesis of dihydroceramides from dihydrosphingosine and very long fatty acyl (C22-C24)-CoAs
-
-
?
additional information
?
-
-
ceramide synthase 2 catalyzes the synthesis of dihydroceramides from dihydrosphingosine and very long fatty acyl (C22-C24)-CoAs
-
-
?
additional information
?
-
both C22:0- and C24:0-CoAs are used effectively for Lass2- and Lass4-dependent ceramide synthesis, and C26:0-, C20:0-, and C18:0-CoAs also act as substrates, albeit weakly. Recombinant Lass2 produces longer ceramides such as C22:0 ceramides and C24:0 ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
both C22:0- and C24:0-CoAs are used effectively for Lass2- and Lass4-dependent ceramide synthesis, and C26:0-, C20:0-, and C18:0-CoAs also act as substrates, albeit weakly. Recombinant Lass2 produces longer ceramides such as C22:0 ceramides and C24:0 ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
-
both C22:0- and C24:0-CoAs are used effectively for Lass2- and Lass4-dependent ceramide synthesis, and C26:0-, C20:0-, and C18:0-CoAs also act as substrates, albeit weakly. Recombinant Lass2 produces longer ceramides such as C22:0 ceramides and C24:0 ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
CerS2 can utilize a wider range of fatty acyl-CoAs but uses mainly C22 to C24
-
-
?
additional information
?
-
-
CerS2 can utilize a wider range of fatty acyl-CoAs but uses mainly C22 to C24
-
-
?
additional information
?
-
CerS2 has a remarkable acyl-CoA specificity, it uses a wider range of acyl-CoAs, synthesizing ceramides containing C20:0, C22:0, C24:1, C24:0, C26:1, and C26:0 fatty acids, but does not synthesize ceramides containing C16:0 fatty acids and synthesizes only low, and statistically insignificant levels of C18:0-ceramide, overview
-
-
?
additional information
?
-
both C22:0- and C24:0-CoAs are used effectively for Lass2- and Lass4-dependent ceramide synthesis, and C26:0-, C20:0-, and C18:0-CoAs also act as substrates, albeit weakly. Recombinant Lass4 produces longer ceramides such as C22:0 and C24:0 ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
both C22:0- and C24:0-CoAs are used effectively for Lass2- and Lass4-dependent ceramide synthesis, and C26:0-, C20:0-, and C18:0-CoAs also act as substrates, albeit weakly. Recombinant Lass4 produces longer ceramides such as C22:0 and C24:0 ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
-
both C22:0- and C24:0-CoAs are used effectively for Lass2- and Lass4-dependent ceramide synthesis, and C26:0-, C20:0-, and C18:0-CoAs also act as substrates, albeit weakly. Recombinant Lass4 produces longer ceramides such as C22:0 and C24:0 ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
enzyme LASS3 shows a relatively broad substrate specificity. Both LASS3 isoforms increase the production of several ceramide species, including C18:0- and C24:0-ceramides. LASS3 exhibits relatively low substrate specificity toward fatty acyl-CoAs. Lysates prepared from LASS3-overproducing cells show significant activity toward several fatty acyl-CoAs, including C18:0-, C22:0-, and C24:0-CoA, with the highest activity for C18:0. C16:0-, C20:0-, and C26:0-CoA are also used as substrates by LASS3, albeit with low activity. LASS3-overproducing cells synthesize ceramide from C18:0-CoA with the highest activity at all concentrations tested. This in vitro result is quite consistent with the in vivo results
-
-
?
additional information
?
-
-
enzyme LASS3 shows a relatively broad substrate specificity. Both LASS3 isoforms increase the production of several ceramide species, including C18:0- and C24:0-ceramides. LASS3 exhibits relatively low substrate specificity toward fatty acyl-CoAs. Lysates prepared from LASS3-overproducing cells show significant activity toward several fatty acyl-CoAs, including C18:0-, C22:0-, and C24:0-CoA, with the highest activity for C18:0. C16:0-, C20:0-, and C26:0-CoA are also used as substrates by LASS3, albeit with low activity. LASS3-overproducing cells synthesize ceramide from C18:0-CoA with the highest activity at all concentrations tested. This in vitro result is quite consistent with the in vivo results
-
-
?
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
D-erythro-sphinganine + arachidoyl-CoA
N-arachidoyl-D-sphinganine + CoA
-
-
-
?
D-erythro-sphinganine + cerotoyl-CoA
N-cerotoyl-D-sphinganine + CoA
-
-
-
?
sphinganine + cerotoyl-CoA
N-cerotoylsphinganine + CoA
low activity
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
-
-
-
-
?
D-erythro-sphinganine + behenoyl-CoA
N-behenoyl-D-sphinganine + CoA
-
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
-
-
-
?
D-erythro-sphinganine + lignoceroyl-CoA
N-lignoceroyl-D-sphinganine + CoA
-
-
-
-
?
D-erythro-sphinganine + nervonoyl-CoA
N-nervonoyl-D-sphinganine + CoA
-
-
-
?
a very-long-chain fatty acyl-CoA + a sphingoid base
a very-long-chain ceramide + CoA
-
-
-
-
?
a very-long-chain fatty acyl-CoA + a sphingoid base
a very-long-chain ceramide + CoA
-
the enzyme synthesizes ceramides with very-long (C22-C24) acyl chains
-
-
?
additional information
?
-
ceramide synthase 2 catalyzes the synthesis of dihydroceramides from dihydrosphingosine and very long fatty acyl (C22-C24)-CoAs
-
-
?
additional information
?
-
-
ceramide synthase 2 catalyzes the synthesis of dihydroceramides from dihydrosphingosine and very long fatty acyl (C22-C24)-CoAs
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
sphingosine 1-phosphate
S1P, noncompetitive inhibition. Bioactive sphingolipid sphingosine 1-phosphate has a regulatory function for CerS2. Residues Arg230 and Arg325 are essential for S1P binding to the S1P1 receptor. Mutation of both residues to alanine completely abolishes the inhibitory effect of S1P on CerS2 without affecting the basal activity of CerS2. Thus, S1P can regulate CerS2 activity via a direct interaction with an S1P receptor-like motif found uniquely in CerS2
additional information
-
fumonisins block sphingosine biosynthesis by inhibiting the conversion of sphinganine to dihydroceramides, which precedes introduction of the 4,5-trans-double bond of sphingosine. Fumonisins, mycotoxins produced by Fusarium moniliforme and a number of other fungi, cause neuronal degeneration, liver and renal toxicity, cancer, and other injury to animals. Fumonisin Bl inhibits complex sphirqolipid synthesis from galactose and sphinganine, effects on the amounts of free sphingosine and sphinganine and on total complex sphingolipids, overview
-
fumonisin B1
-
reversible competitive inhibition, inhibits ceramide synthase in mouse brain microsomes with a competitive-like kinetic behavior with respect to both sphinganine and stearoyl-CoA. Fumonisin B1 inhibits ceramide synthase activity when palmitoyl-CoA, stearoyl-CoA, or lignoceroyl-CoA are used as the co-substrate, cf. EC 2.3.1.297 and 2.3.1.24
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acyl-coenzyme A-binding protein
-
increases the activity of ceramide synthase 2 by more than 2fold. The compound binds very-long chain acyl-CoA esters, which is required for its ability to stimulate enzyme activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten kinetics
-
0.0032
D-erythro-sphinganine
pH 7.5, 37°C, recombinant enzyme, in presence of inhibitor sphingosine 1-phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000006 - 0.0000535
pH 7.4, 37°C, enzyme activity in mouse tissues, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
cell-type-specific expression pattern of CerS2 protein, immunohistochemic analysis
additional information
-
cell-type-specific expression pattern of CerS2 protein, immunohistochemic analysis
additional information
CerS2 tissue expression analysis, comparisons with the other CerS isozymes (CerS1, 3, 4-6). CerS2 mRNA is widely distributed and found at high levels in various tissues
additional information
isozymes mRNAs for Lass2, Lass4, Lass5 and Lass6 are found to be mostly ubiquitous, although no expression is detected in muscle for any of these. Lass2 shows the highest expression in liver, but also high expression in kidney
additional information
isozymes mRNAs for Lass2, Lass4, Lass5 and Lass6 are found to be mostly ubiquitous, although no expression is detected in muscle for any of these. Lass2 shows the highest expression in liver, but also high expression in kidney
additional information
-
isozymes mRNAs for Lass2, Lass4, Lass5 and Lass6 are found to be mostly ubiquitous, although no expression is detected in muscle for any of these. Lass2 shows the highest expression in liver, but also high expression in kidney
additional information
isozymes mRNAs for Lass2, Lass4, Lass5 and Lass6 are found to be mostly ubiquitous, although no expression is detected in muscle for any of these. Lass4 is strongly expressed in skin, with no apparent expression in muscle, testis, or thymus
additional information
isozymes mRNAs for Lass2, Lass4, Lass5 and Lass6 are found to be mostly ubiquitous, although no expression is detected in muscle for any of these. Lass4 is strongly expressed in skin, with no apparent expression in muscle, testis, or thymus
additional information
-
isozymes mRNAs for Lass2, Lass4, Lass5 and Lass6 are found to be mostly ubiquitous, although no expression is detected in muscle for any of these. Lass4 is strongly expressed in skin, with no apparent expression in muscle, testis, or thymus
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
liver microsomal membranes from CerS2 null mice display higher membrane fluidity and show morphological changes. Membrane morphology is studied by fluorescence microscopy, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
Lass proteins are known to contain a TLC [TRAM/Lag1p/CLN8 (ceroid-lipofuscinoses, neuronal 8)] homology domain with the Lag1 motif. Lass family members Lass2, Lass4 and Lass5, but not Lass1, also contain a HOX (homeobox) domain
malfunction
physiological function
evolution
Lass proteins are known to contain a TLC [TRAM/Lag1p/CLN8 (ceroid-lipofuscinoses, neuronal 8)] homology domain with the Lag1 motif. Lass family members Lass2, Lass4 and Lass5, but not Lass1, also contain a HOX (homeobox) domain
malfunction
physiological function
overproduction of LASS3 causes increased levels of C18:0-, C22:0-, and C24:0-ceramides
additional information
malfunction
CerS2-deficient (gene trap) mice exhibit myelin and behavioral abnormalities
malfunction
CerS2 null mouse show ceramide and downstream sphingolipids devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. C16-ceramide levels are elevated, and as a result, total ceramide levels are unaltered. C16-ceramide synthesis in vitro is not increased. Levels of C22-, C24:0-, and C24:1-sphingolipids are reduced by 10-100fold in the CerS2 null mouse, but no significant reduction is seen in C20-sphingolipids. Levels of C26:1- and C26:0-sphingolipids are relatively low in the wild-type, and only a small reduction is observed in the CerS2 null mouse. Levels of sphinganine are significantly elevated by up to 50fold, reminiscent of the effect of the ceramide synthase inhibitor fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways are significantly changed. Total glycerophospholipid and cholesterol levels are unaltered, although there is a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids. Liver microsomal membranes from CerS2 null mice display higher membrane fluidity and show morphological changes. Expression of CerS5 is increased in the Cers2 mutants, and of CerS6 slightly. Mutant phenotype, overview
physiological function
critical role for ceramide synthase 2 in liver homeostasis, molecular changes leading to hepatopathy, overview. Isozyme CerS2 can utilize a wider range of fatty acyl-CoAs but uses mainly C22 to C24. In addition, CerS2 displays complex modes of regulation and has genomic features characteristic of a housekeeping gene, no other CerS genes display these characteristics
physiological function
good correlation between CerS2 mRNA levels and levels of ceramide and sphingomyelin containing long acyl chains in tissues with CerS2 mRNA expression at high levels. The activity of CerS2 can be regulated by another bioactive sphingolipid, sphingosine 1-phosphate (S1P), via interaction of S1P with two residues that are part of an S1P receptor-like motif found only in CerS2
malfunction
Lass4 overproduction caused increases in both middle- and long-chain ceramides
malfunction
-
about 50% of enzyme-null mice develop pheochromocytoma by about 13 months, and the rest shows signs of medullary hyperplasia
malfunction
-
ceramide synthase 2 null mice are more susceptible to dextran sodium sulfate-induced colitis, and their survival rate is markedly decreased compared with that of wild type littermates. In the colon of enzyme-deficient mice, the expression of junctional adhesion molecule-A is markedly decreased and the phosphorylation of myosin light chain 2 is increased. Enzyme deficiency influences intestinal barrier function and the severity of experimental colitis
malfunction
-
enzyme-deficient mice show increased susceptibility to LCMV infection. Reduced levels of invariant natural killer T cells in the thymus of enzyme-null mice is due to their impaired maturation in the thymus
additional information
the N-terminus is essential for catalytic activity
additional information
the N-terminus is essential for catalytic activity
additional information
the N-terminus is essential for catalytic activity
additional information
the N-terminus is essential for catalytic activity
additional information
two transcriptional variants of mouse LASS3 cDNA encoding the LASS3 isoforms, which differ in transcriptional initiation sites and polypeptides length, LASS3 and LASS3-long
additional information
-
two transcriptional variants of mouse LASS3 cDNA encoding the LASS3 isoforms, which differ in transcriptional initiation sites and polypeptides length, LASS3 and LASS3-long
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). CERS2_MOUSE
380
6
45024
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37000
x * 42000, glycosylated enzyme, SDS-PAGE, x * 37000, deglycosylated enzyme, SDS-PAGE
42000
x * 42000, glycosylated enzyme, SDS-PAGE, x * 37000, deglycosylated enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 42000, glycosylated enzyme, SDS-PAGE, x * 37000, deglycosylated enzyme, SDS-PAGE
?
x * 46100, about, isozyme LASS3, sequence calculation, x * 50000, about, isozyme LASS3-long, sequence calculation
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
the N-glycosylation of Lass2 appears as three bands, deglycosylation of Lass2 with PNGase F (N-glycosidase F)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
CerS2 null mouse generation from embryonic stem cells harboring a gene trap (GT) retroviral vector insertion in the first intron of the CerS2 gene, and characterization of the changes in the long chain base and sphingolipid composition of livers from these mice. Ceramide and downstream sphingolipids are devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. C16-ceramide levels are elevated, and as a result, total ceramide levels are unaltered. C16-ceramide synthesis in vitro is not increased. Levels of sphinganine are significantly elevated by up to 50fold, reminiscent of the effect of the ceramide synthase inhibitor fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways are significantly changed. Total glycerophospholipid and cholesterol levels are unaltered, although there is a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids
additional information
-
CerS2 null mouse generation from embryonic stem cells harboring a gene trap (GT) retroviral vector insertion in the first intron of the CerS2 gene, and characterization of the changes in the long chain base and sphingolipid composition of livers from these mice. Ceramide and downstream sphingolipids are devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. C16-ceramide levels are elevated, and as a result, total ceramide levels are unaltered. C16-ceramide synthesis in vitro is not increased. Levels of sphinganine are significantly elevated by up to 50fold, reminiscent of the effect of the ceramide synthase inhibitor fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways are significantly changed. Total glycerophospholipid and cholesterol levels are unaltered, although there is a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids
additional information
Lass4 overproduction causing increases in both middle- and long-chain ceramides
additional information
Lass4 overproduction causing increases in both middle- and long-chain ceramides
additional information
-
Lass4 overproduction causing increases in both middle- and long-chain ceramides
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic tree, recombinant expression of HA-tagged enzyme in HEK-293T cells
gene CERS2, quantitative real-time PCR expression analysis, recombinant expression of C-terminally HA-tagged CerS2 in the endoplasmic reticulum of yeast cells, recombinant expression of FLAG-tagged CerS2 in HEK-293T cells
DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic tree, recombinant expression of HA-tagged enzyme in HEK-293T cells
gene CERS3, DNA and amino acid sequence determination and analysis, cloning of two transcriptional variants of LASS3 cDNA, which encode a 384-amino-acid protein (LASS3) and a 419-amino-acid protein (LASS3-long), reverse transcription (RT)-PCR expression analysis, recombinant expression in HEK-293T cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ceramide synthase 2 activity is significantly reduced in the testes of acyl-coenzyme A-binding protein-deficient mice
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kremser, C.; Klemm, A.L.; van Uelft, M.; Imgrund, S.; Ginkel, C.; Hartmann, D.; Willecke, K.
Cell-type-specific expression pattern of ceramide synthase 2 protein in mouse tissues
Histochem. Cell Biol.
140
533-547
2013
Mus musculus (Q924Z4), Mus musculus, Mus musculus C57BL/6 (Q924Z4)
Mizutani, Y.; Kihara, A.; Igarashi, Y.
Mammalian Lass6 and its related family members regulate synthesis of specific ceramides
Biochem. J.
390
263-271
2005
Mus musculus (Q924Z4), Mus musculus (Q9D6J1), Mus musculus
Mizutani, Y.; Kihara, A.; Igarashi, Y.
LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity
Biochem. J.
398
531-538
2006
Mus musculus (Q1A3B0), Mus musculus
Merrill, A.H.; van Echten, G.; Wang, E.; Sandhoff, K.
Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ
J. Biol. Chem.
268
27299-27306
1993
Mus musculus, Mus musculus NMRI
Laviad, E.L.; Albee, L.; Pankova-Kholmyansky, I.; Epstein, S.; Park, H.; Merrill, A.H.; Futerman, A.H.
Characterization of ceramide synthase 2 tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate
J. Biol. Chem.
283
5677-5684
2008
Mus musculus (Q924Z4), Mus musculus C57BL/6 (Q924Z4)
Pewzner-Jung, Y.; Brenner, O.; Braun, S.; Laviad, E.L.; Ben-Dor, S.; Feldmesser, E.; Horn-Saban, S.; Amann-Zalcenstein, D.; Raanan, C.; Berkutzki, T.; Erez-Roman, R.; Ben-David, O.; Levy, M.; Holzman, D.; Park, H.; Nyska, A.; Merrill, A.H.; Futerman, A.H.
A critical role for ceramide synthase 2 in liver homeostasis II. insights into molecular changes leading to hepatopathy
J. Biol. Chem.
285
10911-10923
2010
Mus musculus (Q924Z4), Mus musculus
Ferreira, N.S.; Engelsby, H.; Neess, D.; Kelly, S.L.; Volpert, G.; Merrill, A.H.; Futerman, A.H.; Faergeman, N.J.
Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein
J. Biol. Chem.
292
7588-7597
2017
Mus musculus
Park, W.J.; Brenner, O.; Kogot-Levin, A.; Saada, A.; Merrill, A.H.; Pewzner-Jung, Y.; Futerman, A.H.
Development of pheochromocytoma in ceramide synthase 2 null mice
Endocr. Relat. Cancer
22
623-632
2015
Mus musculus
Saroha, A.; Pewzner-Jung, Y.; Ferreira, N.S.; Sharma, P.; Jouan, Y.; Kelly, S.L.; Feldmesser, E.; Merrill, A.H.; Trottein, F.; Paget, C.; Lang, K.S.; Futerman, A.H.
Critical role for very-long chain sphingolipids in invariant natural killer T cell development and homeostasis
Front. Immunol.
8
1386
2017
Mus musculus
Kim, Y.R.; Volpert, G.; Shin, K.O.; Kim, S.Y.; Shin, S.H.; Lee, Y.; Sung, S.H.; Lee, Y.M.; Ahn, J.H.; Pewzner-Jung, Y.; Park, W.J.; Futerman, A.H.; Park, J.W.
Ablation of ceramide synthase 2 exacerbates dextran sodium sulphate-induced colitis in mice due to increased intestinal permeability
J. Cell. Mol. Med.
21
3565-3578
2017
Mus musculus
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