Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
3-dehydrosphinganine + palmitoyl-CoA
N-palmitoyl-3-dehydrosphinganine
-
-
-
-
?
acyl-CoA + sphingosine
?
LASS5 is the major ceramide synthase gene product involved in sphingolipid production that may also regulate PtdCho metabolism in pulmonary epithelia
-
-
?
D-erythro-sphinganine + palmitoyl-CoA
N-palmitoyl-D-sphinganine
-
low activity
-
-
?
palmitoyl-CoA + sphingosine
CoA + N-palmitoylsphingosine
-
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoyl-DL-dihydrosphingosine + CoA
-
-
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
sphingosine + lauroyl-CoA
N-lauroylsphingosine + CoA
low activity
-
-
?
sphingosine + myristoyl-CoA
N-myristoylsphingosine + CoA
-
-
-
?
sphingosine + oleoyl-CoA
N-oleoylsphingosine + CoA
low activity
-
-
?
sphingosine + palmitoyl-CoA
N-palmitoylsphingosine + CoA
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
low activity
-
-
?
tetracosanoyl-CoA + sphingosine
CoA + N-tetracosanoylsphingosine
-
-
-
?
additional information
?
-
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
-
-
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
-
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
-
-
-
-
?
sphingosine + palmitoyl-CoA
N-palmitoylsphingosine + CoA
-
-
-
?
sphingosine + palmitoyl-CoA
N-palmitoylsphingosine + CoA
-
-
-
?
additional information
?
-
the enzyme catalyzes the synthesis of significantly more 17C16- and 17C24:1-ceramides and significantly less 17C22:0-, 17C24:0, and 17C26:0-ceramides in vivo, analysis of sphingosine and ceramidases in different cells, overview
-
-
?
additional information
?
-
both Lass5- and Lass6-overproducing cells exhibit high dihydroceramide synthesis activity using C16:0- and C14:0-CoAs and low activity with C12:0- and C18:0-CoAs. On the other hand, whereas the Lass5-overproducing cells demonstrates significant C18:1-ceramide synthesis, the Lass6-overproducing cells do not show any such increase. Recombinant Lass6 produces shorter ceramide species (C14:0- and C16:0-ceramides) in transgenic HEK-293T cells
-
-
?
additional information
?
-
both Lass5- and Lass6-overproducing cells exhibit high dihydroceramide synthesis activity using C16:0- and C14:0-CoAs and low activity with C12:0- and C18:0-CoAs. On the other hand, whereas the Lass5-overproducing cells demonstrates significant C18:1-ceramide synthesis, the Lass6-overproducing cells do not show any such increase. Recombinant Lass6 produces shorter ceramide species (C14:0- and C16:0-ceramides) in transgenic HEK-293T cells
-
-
?
additional information
?
-
-
both Lass5- and Lass6-overproducing cells exhibit high dihydroceramide synthesis activity using C16:0- and C14:0-CoAs and low activity with C12:0- and C18:0-CoAs. On the other hand, whereas the Lass5-overproducing cells demonstrates significant C18:1-ceramide synthesis, the Lass6-overproducing cells do not show any such increase. Recombinant Lass6 produces shorter ceramide species (C14:0- and C16:0-ceramides) in transgenic HEK-293T cells
-
-
?
additional information
?
-
both Lass5- and Lass6-overproducing cells exhibit high dihydroceramide synthesis activity using C16:0- and C14:0-CoAs and low activity with C12:0- and C18:0-CoAs. On the other hand, whereas the Lass5-overproducing cells demonstrates significant C18:1-ceramide synthesis, the Lass6-overproducing cells do not show any such increase. The recombinant Lass5 shows a preference for C16 substrates in transgenic HEK-293T cells
-
-
?
additional information
?
-
both Lass5- and Lass6-overproducing cells exhibit high dihydroceramide synthesis activity using C16:0- and C14:0-CoAs and low activity with C12:0- and C18:0-CoAs. On the other hand, whereas the Lass5-overproducing cells demonstrates significant C18:1-ceramide synthesis, the Lass6-overproducing cells do not show any such increase. The recombinant Lass5 shows a preference for C16 substrates in transgenic HEK-293T cells
-
-
?
additional information
?
-
-
both Lass5- and Lass6-overproducing cells exhibit high dihydroceramide synthesis activity using C16:0- and C14:0-CoAs and low activity with C12:0- and C18:0-CoAs. On the other hand, whereas the Lass5-overproducing cells demonstrates significant C18:1-ceramide synthesis, the Lass6-overproducing cells do not show any such increase. The recombinant Lass5 shows a preference for C16 substrates in transgenic HEK-293T cells
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
-
-
fumonisin B1
-
a natural product of the fungus Fusarium moniliforme that acts as a mycotoxin in mammalian cells. It does not affect the rate of cell proliferation or cell viability of P338 cells during 24 h at 0.1 mM, but inhibits 80% and 60% of the apoptotic lethal effect produced by 200 nM and 300 nM daunorubicin, respectively. Increasing the dose of daunorubicin to greater than 500 nM, it also abrogates the inhibitory effect of fumonisin B1
fumonisin B1
knockdown using fumonisin B 1 reduces ceramide synthase activity by 78%
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
additional information
no enzyme inhibition by curcumin
-
additional information
-
enzyme activitiy does not change by pretreating the endoplasmic reticulum-derived membrane vesicles with detergent
-
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
-
brenda
-
brenda
-
-
brenda
-
brenda
-
brenda
-
-
brenda
-
brenda
-
brenda
-
brenda
mouse lung epithelial cell
brenda
-
cerebellar
brenda
-
-
brenda
-
brenda
high expression level
brenda
-
-
brenda
-
brenda
-
brenda
-
brenda
-
brenda
high expression level
brenda
-
brenda
high expression level
brenda
-
-
brenda
-
brenda
-
brenda
LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia
brenda
high enzyme expression level, pulmonary LASS5 is developmentally regulated, but its expression is spatially and gender-nonspecific
brenda
additional information
in primary type II epithelial cells, murine lung fibroblasts, and MLE cells, LASS5 is the predominant ceramide synthase species identified
brenda
additional information
-
in primary type II epithelial cells, murine lung fibroblasts, and MLE cells, LASS5 is the predominant ceramide synthase species identified
brenda
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. No expression of Lass6 is observed in heart, muscle, spleen or stomach. Lass6 is most highly expressed in kidney, followed by brain
brenda
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. No expression of Lass6 is observed in heart, muscle, spleen or stomach. Lass6 is most highly expressed in kidney, followed by brain
brenda
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. No expression of Lass6 is observed in heart, muscle, spleen or stomach. Lass6 is most highly expressed in kidney, followed by brain
brenda
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. The highest expression of Lass5 is in testis, and the expression in kidney is also high
brenda
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. The highest expression of Lass5 is in testis, and the expression in kidney is also high
brenda
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. The highest expression of Lass5 is in testis, and the expression in kidney is also high
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
evolution
murine Lass6 is a member of the mouse Lass family. It exhibits the highest identity with Lass5 (61.7% identity and 68.2% similarity) and the lowest identity with Lass1 (16.0% identity and 27.4%similarity). 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
decreased enzyme expression induces endoplasmic reticulum stress and apoptosis in head and neck squamous carcinoma cells but not in A-549, MCF-7, or SW-480 cells, which are derived from lung, breast, and colon cancer, respectively, detailed overview
malfunction
knockdown using fumonisin B 1 or LASS5 small, interfering RNA reduced ceramide synthase activity by 78% or 45%, respectively. Exogenously expressed LASS5 in lung epithelia is membrane-associated, triggering increased ceramide synthesis. Compared with control cells, cells transfected with LASS5 siRNA exhibit a 43% increase in rates of phosphatidylcholine synthesis
metabolism
due to the highly dynamic nature of sphingolipid metabolism, alterations in the expression of CerS6 may have impacts beyond increased generation of C16-ceramide
metabolism
LASS5 expression alone reduces choline incorporation into phosphatidylcholine by 26%, whereas coexpression of LASS5 with sphingomyelinase produces a nearly 40% reduction in phosphatidylcholine synthesis
metabolism
-
serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase are responsible for the first steps in sphingolipid biosynthesis forming 3-oxosphinganine, sphinganine, and dihydroceramide, respectively
metabolism
-
the sphingomyelin pathway, which is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide, signals apoptosis for tumor necrosis factor a, Fas, and ionizing radiation
physiological function
activity of CerS in the salvage pathway in which sphingosine is recycled into ceramides. Upregulation of CerS6 expression increases C16-ceramide generation at the expense of very long chain ceramides. Increased expression of acid ceramidase in response to CerS6 expression occurs via a JNK-AP1-dependent mechanism and is important for survival. Enzyme CerS6 may transcriptionally activate the expression of acid ceramidase (ASAH1)
physiological function
-
ceramide synthase mediates daunorubicin-induced apoptosis, an alternative mechanism for generating death signals. Ceramide synthesis appears obligatory for daunorubicin-induced apoptosis, since fumonisin B1, a natural specific inhibitor of ceramide synthase, blocks daunorubicin-induced ceramide elevation and apoptosis. Ceramide mimics daunorubicin in inducing apoptosis
physiological function
isozyme CerS5 sensitizes cells to doxorubicin and vincristine
physiological function
LASS5 is the major ceramide synthase gene product involved in sphingolipid production that may also regulate PtdCho metabolism in pulmonary epithelia. LASS5 regulates surfactant phosphatidylcholine (PtdCho) synthesis
physiological function
CerS6 overexpression elevates TNFalpha secretion via p38 mitogen-activated protein kinase activation. The treatment of CerS6 overexpressing cells with palmitate synergistically increases cytokine secretion. Neither palmitate treatment nor CerS6 overexpression alter lipopolysaccharide-induced cytokine secretion
physiological function
inhibition by fumosinin and siRNA for isoforms CerS5 or CerS6 suppresses myristate-induced C14-ceramide generation and XBP1 splicing. Increased XBP1 splicing induces the downstream expression of IL-6 in a CerS5/CerS6-dependent manner. A myristate-enriched milk fat-based diet, but not a lard-based diet, increases C14-ceramide, XBP1 splicing and IL-6 expression in vivo
physiological function
inhibition by fumosinin and siRNA for isoforms CerS5 or CerS6 suppresses myristate-induced C14-ceramide generation and XBP1 splicing. Increased XBP1 splicing induces the downstream expression of IL-6 in a CerS5/CerS6-dependent manner. A myristate-enriched milk fat-based diet, but not a lard-based diet, increases C14-ceramide,XBP1 splicing and IL-6 expression in vivo
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
H212A
site-directed mutagenesis
N18Q
site-directed mutagenesis, a glycosylation site mutant
N285Q
site-directed mutagenesis, a putative glycosylation site mutant
S341A
mutation in potential phosphorylation site, about 45% of wild-type activity, substrate tetracosanoyl-CoA
S349A
mutation in potential phosphorylation site, about 90% of wild-type activity, substrate tetracosanoyl-CoA
T346A
mutation in potential phosphorylation site, about 80% of wild-type activity, substrate tetracosanoyl-CoA
additional information
enzyme knockout by shRNA
additional information
in HEK-293 cells, ectopically expressed murine CerS5 only sensitized cells to doxorubicin and vincristine
additional information
LASS5 gene silencing by siRNAexogenously expressed LASS5 in lung epithelia is membrane-associated, triggering increased ceramide synthesis. Maximal inhibition is achieved when LASS5 is coexpressed with a plasmid encoding a neutral sphingomyelinase involved in sphingomyelin hydrolysis. Compared with control cells, cells transfected with LASS5 siRNA exhibit a 43% increase in rates of phosphatidylcholine synthesis
additional information
-
LASS5 gene silencing by siRNAexogenously expressed LASS5 in lung epithelia is membrane-associated, triggering increased ceramide synthesis. Maximal inhibition is achieved when LASS5 is coexpressed with a plasmid encoding a neutral sphingomyelinase involved in sphingomyelin hydrolysis. Compared with control cells, cells transfected with LASS5 siRNA exhibit a 43% increase in rates of phosphatidylcholine synthesis
additional information
no loss of activity is observed for the unglycosylated mutant (HA-tagged Lass6-N18Q) when compared with either the glycosylated mutant HA-tagged Lass6-N285Q or the glycosylated wild-type Lass6
additional information
no loss of activity is observed for the unglycosylated mutant (HA-tagged Lass6-N18Q) when compared with either the glycosylated mutant HA-tagged Lass6-N285Q or the glycosylated wild-type Lass6
additional information
-
no loss of activity is observed for the unglycosylated mutant (HA-tagged Lass6-N18Q) when compared with either the glycosylated mutant HA-tagged Lass6-N285Q or the glycosylated wild-type Lass6
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic tree, recombinant expression of HA-tagged enzyme 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, and recombinant expression of C-terminally GFP-tagged Lass6
expression of wild-type and mutant enzymes in Escherichia coli strain BJ5183, and transient expression in HEK293A cells, HT29 cells, and SW620 cells from an adenovirus vector
gene CERS5, stable recombinant ectopic overexpression of N-terminally FLAG3-tagged CerS5 in HEK-293 or HeLa cells, the level of FLAG-tagged CerS5 remains constant after exposure to cisplatin, doxorubicin, or UV light
gene Cers5, transient recombinant expression of His-tagged LASS5 in MLE cells
MLE cells transiently transfected with His-tagged LASS5 plasmid
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Xu, Z.; Zhou, J.; McCoy, D.M.; Mallampalli, R.K.
LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia
J. Lipid Res.
46
1229-1238
2005
Mus musculus (Q9D6K9), Mus musculus
brenda
Tirodkar, T.S.; Lu, P.; Bai, A.; Scheffel, M.J.; Gencer, S.; Garrett-Mayer, E.; Bielawska, A.; Ogretmen, B.; Voelkel-Johnson, C.
Expression of ceramide synthase 6 transcriptionally activates acid ceramidase in a c-Jun N-terminal kinase (JNK)-dependent manner
J. Biol. Chem.
290
13157-13167
2015
Mus musculus (Q8C172)
brenda
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 (Q8C172), Mus musculus (Q9D6K9), Mus musculus
brenda
Sridevi, P.; Alexander, H.; Laviad, E.L.; Pewzner-Jung, Y.; Hannink, M.; Futerman, A.H.; Alexander, S.
Ceramide synthase 1 is regulated by proteasomal mediated turnover
Biochim. Biophys. Acta
1793
1218-1227
2009
Mus musculus (Q9D6K9)
brenda
Bose, R.; Verheji, M.; Haimovitz-Friedman, A.; Scotto, K.; Fuks, Z.; Kolesnick, R.
Ceramide synthase mediates daunorubicin-induced apoptosis an alternative mechanism for generating death signals
Cell
82
405-414
1995
Homo sapiens, Mus musculus
brenda
Choi, S.; Snider, J.M.; Olakkengil, N.; Lambert, J.M.; Anderson, A.K.; Ross-Evans, J.S.; Cowart, L.A.; Snider, A.J.
Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cells
FASEB J.
32
5724-5736
2018
Mus musculus (Q8C172), Mus musculus (Q9D6K9)
brenda
Mandon, E.C.; Ehses, I.; Rother, J.; van Echten, G.; Sandhoff, K.
Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver
J. Biol. Chem.
267
11144-11148
1992
Mus musculus
brenda
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
brenda
Sassa, T.; Hirayama, T.; Kihara, A.
Enzyme activities of the ceramide synthases CERS2-6 are regulated by phosphorylation in the C-terminal region
J. Biol. Chem.
291
7477-7487
2016
Homo sapiens (Q8IU89), Homo sapiens (Q8N5B7), Homo sapiens (Q96G23), Homo sapiens (Q9HA82), Homo sapiens (Q9NTG7), Mus musculus (Q924Z4), Mus musculus
brenda
Xu, Z.; Zhou, J.; McCoy, D.M.; Mallampalli, R.K.
LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia
J. Lipid Res.
46
1229-1238
2005
Mus musculus (Q9D6K9), Mus musculus, Mus musculus C57BL/6 (Q9D6K9)
brenda
Williams, B.; Correnti, J.; Oranu, A.; Lin, A.; Scott, V.; Annoh, M.; Beck, J.; Furth, E.; Mitchell, V.; Senkal, C.E.; Obeid, L.; Carr, R.M.
A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis
FASEB J.
32
130-142
2018
Homo sapiens (Q6ZMG9), Homo sapiens, Mus musculus (Q8C172), Mus musculus
brenda
Kim, M.H.; Ahn, H.K.; Lee, E.J.; Kim, S.J.; Kim, Y.R.; Park, J.W.; Park, W.J.
Hepatic inflammatory cytokine production can be regulated by modulating sphingomyelinase and ceramide synthase 6
Int. J. Mol. Med.
39
453-462
2017
Mus musculus (Q8C172)
brenda