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Information on EC 2.3.1.24 - sphingosine N-acyltransferase and Organism(s) Mus musculus and UniProt Accession Q9D6K9

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IUBMB Comments
Acts on sphingosine or its 2-epimer.
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This record set is specific for:
Mus musculus
UNIPROT: Q9D6K9
Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Synonyms
(dihydro)ceramide synthase, acyl-CoA : sphingosine N-acyltramferase, acyl-CoA : sphingosine N-acyltransferase, acyltransferase, sphingosine, C16:0-CerS, ceramide synthase, ceramide synthase 4, ceramide synthase 5, ceramide synthase 6, ceramide synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acyltransferase, sphingosine
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-
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ceramide synthase
244
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ceramide synthase 5
280835
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ceramide synthase 6
280834
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ceramide synthetase
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-
-
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CerS5
280835
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CerS6
280834
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LAG1 longevity assurance homolog 5
280835
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Lass6
280834
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longevity assurance homolog 5
280835
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SpAT
244
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sphinganine N-acyl transferase synthase
244
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sphinganine N-acyltransferase
244
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sphingosine acyltransferase
-
-
-
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TRAM homolog 4
280835
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translocating chain-associating membrane protein homolog 4
280835
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trh1-like
280834
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trh4
280835
-
additional information
244
see also EC 2.3.1.299 and EC 2.3.1.297
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
acyl-CoA:sphingosine N-acyltransferase
Acts on sphingosine or its 2-epimer.
CAS REGISTRY NUMBER
COMMENTARY hide
37257-09-3
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acyl-CoA + sphingosine
?
show the reaction diagram
LASS5 is the major ceramide synthase gene product involved in sphingolipid production that may also regulate PtdCho metabolism in pulmonary epithelia
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-
?
palmitoyl-CoA + sphingosine
CoA + N-palmitoyl-sphingosine
show the reaction diagram
-
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
show the reaction diagram
-
-
-
-
?
sphingosine + lauroyl-CoA
N-lauroylsphinganine + CoA
show the reaction diagram
-
low activity
-
-
?
sphingosine + myristoyl-CoA
N-myristoylsphinganine + CoA
show the reaction diagram
-
-
-
-
?
sphingosine + oleoyl-CoA
N-oleoylsphinganine + CoA
show the reaction diagram
-
low activity
-
-
?
sphingosine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
show the reaction diagram
-
-
-
-
?
sphingosine + palmitoyl-CoA
N-palmitoylsphingosine + CoA
show the reaction diagram
-
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphinganine + CoA
show the reaction diagram
-
low activity
-
-
?
3-dehydrosphinganine + palmitoyl-CoA
N-palmitoyl-3-dehydrosphinganine
show the reaction diagram
-
-
-
-
?
D-erythro-sphinganine + palmitoyl-CoA
N-palmitoyl-D-sphinganine
show the reaction diagram
-
low activity
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoyl-DL-dihydrosphingosine + CoA
show the reaction diagram
-
-
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine
show the reaction diagram
-
-
-
-
?
sphingosine + lauroyl-CoA
N-lauroylsphingosine + CoA
show the reaction diagram
-
low activity
-
-
?
sphingosine + myristoyl-CoA
N-myristoylsphingosine + CoA
show the reaction diagram
-
-
-
-
?
sphingosine + palmitoyl-CoA
N-palmitoylsphingosine + CoA
show the reaction diagram
-
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
show the reaction diagram
-
low activity
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acyl-CoA + sphingosine
?
show the reaction diagram
LASS5 is the major ceramide synthase gene product involved in sphingolipid production that may also regulate PtdCho metabolism in pulmonary epithelia
-
-
?
sphinganine + palmitoyl-CoA
N-palmitoylsphinganine + CoA
show the reaction diagram
-
-
-
-
?
additional information
?
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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
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
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activates
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
fumonisin B1
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knockdown using fumonisin B 1 reduces ceramide synthase activity by 78%
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
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fumonisin B1
SP600125
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-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
daunorubicin
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an anthracycline used in the treatment of leukemia, increases the enzyme activity and ceramide production, and inhibits the apoptosis of leukmeia cells, 70% increase of activity in microsomes at 0.01 mM in treatment of cell cultures for 6 h
additional information
-
vincristine (100 nM), methotrexate (200 nM), etoposide (0.003 mM), and cis-platinum (0.05 mM) do not stimulate ceramide synthase
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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kinetics in presence of daunorubicin
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
inhibition kinetics
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000049
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endoplasmic reticulum-derived membrane vesicles, pH 7.5, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
7.5
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assay at
7.2
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assay at
7.5
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
37
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assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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mouse lung epithelial cell
Manually annotated by BRENDA team
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high expression level
Manually annotated by BRENDA team
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high expression level
Manually annotated by BRENDA team
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high expression level
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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cerebellar
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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membrane-associated
Manually annotated by BRENDA team
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mainly, the enzyme faces the cytosolic side of the endoplasmic reticulum, so that substrates have free access to the active site
Manually annotated by BRENDA team
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the C-terminus of Lass6 is exposed to the cytosolic side of the endoplasmic reticulum membrane
Manually annotated by BRENDA team
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low enzyme level
Manually annotated by BRENDA team
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membrane vesicles derived from endoplasmic reticlum and Golgi membranes, mouse liver smooth and rough ER vesicles
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
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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
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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
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LASS5 expression alone reduces choline incorporation into phosphatidylcholine by 26%, whereas coexpression of LASS5 with sphingomyelinase produces a nearly 40% reduction in phosphatidylcholine synthesis
physiological function
evolution
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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
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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
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
CERS5_MOUSE
414
5
48167
Swiss-Prot
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 50000, recombinant FLAG3-tagged CerS5, SDS-PAGE
?
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x * 44800, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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the N-glycosylation of Lass5 appears as two bands, deglycosylation of Lass5 with PNGase F (N-glycosidase F)
glycoprotein
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Asn18, but not Asn285, of Lass6 is glycosylated, deglycosylation of Lass6 with PNGase F (N-glycosidase F). Lass6 is modified by N-glycosylation of a high-mannose and/or hybrid type. N-glycosylation is not essential for the dihydroceramide synthase activity of Lass6
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H212A
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site-directed mutagenesis
N18Q
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site-directed mutagenesis, a glycosylation site mutant
N285Q
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site-directed mutagenesis, a putative glycosylation site mutant
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged LASS5 from MLE cells by nickel affinity chromatography and ultrafiltration
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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
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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
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gene Cers5, transient recombinant expression of His-tagged LASS5 in MLE cells
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MLE cells transiently transfected with His-tagged LASS5 plasmid
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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
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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
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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, Mus musculus (Q9D6K9)
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
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, Mus musculus (Q8C172), Mus musculus (Q9D6K9)
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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, Mus musculus (Q9D6K9), Mus musculus C57BL/6 (Q9D6K9)
Manually annotated by BRENDA team
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