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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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Select one or more organisms in this record:
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
ceramide synthase, cers2, cers6, lass2, cers1, cers4, cers5, lass5, lag1p, cers3, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acyltransferase, sphingosine
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-
-
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ceramide synthase
ceramide synthase 2
280837
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ceramide synthase 6
280834
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ceramide synthetase
-
-
-
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CerS2
CerS3
244
-
CerS6
280834
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LAG1 longevity assurance homolog 1
280838
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LAG1 longevity assurance homolog 2
280837
-
LAG1 longevity assurance homolog 4
280836
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LAG1 longevity assurance homolog 5
280835
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LAG1 longevity assurance homolog 6
280834
-
Lass
280835
-
LASS1
Lass2
280837
-
LASS3
280841
-
Lass4
280836
-
LASS5
280835
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Lass6
280834
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longevity assurance homolog 5
280835
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longevity assurance homologue 3
280841
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sphingosine acyltransferase
-
-
-
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TRAM homolog 1
280836
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TRAM homolog 3
280837
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TRAM homolog 4
280835
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translocating chain-associating membrane protein homolog 1
280836
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translocating chain-associating membrane protein homolog 3
280837
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translocating chain-associating membrane protein homolog 4
280835
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UOG-1 protein
280838
-
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
-
-
?
acyl-CoA + sphingosine
CoA + N-acylsphingosine
show the reaction diagram
palmitoyl-CoA + sphingosine
CoA + N-palmitoyl-sphingosine
show the reaction diagram
-
-
-
-
?
2-hydroxystearoyl-CoA + dihydrosphingosine
CoA + N-(2-hydroxystearoyl)-dihydrosphingosine
show the reaction diagram
acyl-CoA + sphingosine
CoA + N-acylsphingosine
show the reaction diagram
nervonoyl-CoA + NBD-sphinganine
CoA + ?
show the reaction diagram
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
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-
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stearoyl-CoA + sphingosine
CoA + stearoylsphingosine
show the reaction diagram
-
-
-
-
-
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
-
-
?
acyl-CoA + sphingosine
CoA + N-acylsphingosine
show the reaction diagram
P27545, Q8C172, Q924Z4, Q9D6J1, Q9D6K9
Lass6 produces shorter ceramide species (C14:0- and C16:0-ceramides)
-
-
?
acyl-CoA + sphingosine
CoA + N-acylsphingosine
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
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fumonisin B1
SP600125
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-
additional information
-
no enzyme inhibition by curcumin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
daunorubicin
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0.01 mM, treatment of cell cultures for 6 h, 70% increase of activity in microsomes; anthracycline used in the treatment of leukemia
sphingosine 1-phosphate
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activity of isoform CerS2 can be regulated by sphingosine 1-phosphate, via interaction with two residues that are part of an sphingosine 1-phosphate receptor-like motif found only in CerS2
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.035
sphinganine
-
-
0.003
stearoyl-CoA
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-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000006 - 0.0000535
pH 7.4, 37°C, enzyme activity in mouse tissues, overview
0.000049
-
activity in endoplasmic reticulum vesicles from liver
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia
Manually annotated by BRENDA team
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reduced ceramide synthase activity in the inner epidermis of aged skin. Reduced ceramide synthase activity in the inner epidermis correlates with reduced capacity for permeability barrier repair in aging
Manually annotated by BRENDA team
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high expression level
Manually annotated by BRENDA team
of cerebrum and cerebellum as well as in the white matter
Manually annotated by BRENDA team
LASS3 mRNA expression is limited almost solely to testis, LASS3 plays an important role in this gland
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
the N-terminal region faces the luminal side and the C-terminal region the cytosolic side of the endoplasmic reticulum membrane
Manually annotated by BRENDA team
the N-terminal region faces the luminal side and the C-terminal region the cytosolic side of the endoplasmic reticulum membrane
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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due to the highly dynamic nature of sphingolipid metabolism, alterations in the expression of CerS6 may have impacts beyond increased generation of C16-ceramide
physiological function
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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)
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
CERS5_MOUSE
414
5
48167
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
LITERATURE
?
x * 42000, glycosylated enzyme, SDS-PAGE, x * 37000, deglycosylated enzyme, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
Lass5 is N-glycosylated at the N-terminal Asn residue
glycoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D210N
-
mutation results in loss of activity in cells and in vitro
D213N
-
mutation results in loss of activity in cells and in vitro
H182D
-
mutation results in loss of activity in cells and in vitro
H183D
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mutation results in loss of activity in cells and in vitro
H212A
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site-directed mutagenesis
K220L
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mutant enzyme is able to increase cellular C18 and C18:1 ceramide levels to a similar or slightly lesser extent than wild-type LASS1
L189E
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mutation results in loss of activity in cells and in vitro
L216E
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mutation results in loss of activity in cells and in vitro
S193A
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mutant enzyme is able to increase cellular C18 and C18:1 ceramide levels to a similar or slightly lesser extent than wild-type LASS1
additional information
-
enzyme knockout by shRNA
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
MLE cells transiently transfected with His-tagged LASS5 plasmid
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expression in HEK-293T cell and HeLa cell
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expression in HeLa cells
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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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gene cers2, expression analysis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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., Jr.; 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
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
Jensen, J.M.; Forl, M.; Winoto-Morbach, S.; Seite, S.; Schunck, M.; Proksch, E.; Schutze, S.
Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging
Exp. Dermatol.
14
609-618
2005
Mus musculus
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 (P27545), Mus musculus (Q8C172), Mus musculus (Q924Z4), Mus musculus (Q9D6J1), Mus musculus (Q9D6K9)
Manually annotated by BRENDA team
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, Mus musculus (Q1A3B0)
Manually annotated by BRENDA team
Spassieva, S.; Seo, J.G.; Jiang, J.C.; Bielawski, J.; Alvarez-Vasquez, F.; Jazwinski, S.M.; Hannun, Y.A.; Obeid, L.M.
Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity
J. Biol. Chem.
281
33931-33938
2006
Mus musculus
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)
Manually annotated by BRENDA team
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
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Mizutani, Y.; Kihara, A.; Chiba, H.; Tojo, H.; Igarashi, Y.
2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length
J. Lipid Res.
49
2356-2364
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
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, Mus musculus (Q924Z4), Mus musculus C57BL/6 (Q924Z4)
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
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