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Information on EC 3.5.1.23 - ceramidase and Organism(s) Rattus norvegicus and UniProt Accession Q91XT9
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3.5.1.23 ceramidaseSpecify your search results
Word Map
- 3.5.1.23
-
adipor1
- sphingolipids
- obesity
-
adipokine
- agonist
- sphingomyelinase
- sphingomyelin
- lysosomal
- farber
-
obese
- leptin
- adipocytes
-
amp-activated
- sphingosine-1-phosphate
- peroxisome
- cardiovascular
-
proliferator-activated
- triglyceride
-
globular
-
insulin-sensitizing
-
high-fat
- tnf
- smases
-
adipocytokine
-
adipocyte-derived
-
monophosphate-activated
-
anti-atherogenic
-
t-cadherin
- steatosis
-
adiposity
- glucosylceramide
- glycosphingolipids
-
obesity-related
-
antidiabetic
- 1-phosphate
-
seven-transmembrane
- gaucher
- dihydrosphingosine
-
p-ampk
- palmitoyltransferase
-
homa-ir
-
sphingoid
- hoarseness
-
ceramide-induced
- sphinganine
-
ceramide-mediated
- dihydroceramide
-
myoclonic
-
adipocyte-secreted
- analysis
- pharmacology
- drug development
- medicine
-
hypoadiponectinemia
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
adipor2, adiponectin receptor, ceramidase, acid ceramidase, asah1, neutral ceramidase, acdase, ncdase, acer2, acer3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acylsphingosine deacylase
-
-
-
-
glycosphingolipid ceramide deacylase
-
-
-
-
N-acylsphingosine amidohydrolase
-
-
-
-
PHP32
-
-
-
-
Putative 32 KDA heart protein
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a ceramide + H2O = a carboxylate + sphingosine
neutral CDase contains a zinc ion in the active site that functions as a catalytic center, and the hydrolysis of the N-acyl linkage in ceramide proceeds through a mechanism that is similar to that described for zinc-dependent carboxypeptidase, reaction mechanism, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
N-acylsphingosine amidohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY
37289-06-8
-
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
4-nitrobenzo-2-oxa-1,3-diazoyl-N-dodecanoylsphingosine + H2O
4-nitrobenzo-2-oxa-1,3-diazoyl-dodecanoic acid + sphingosine
much faster hydrolysis than of N-lauroylsphingosine
-
-
?
C12-4-nitrobenzo-2-oxa-1,3-diazole-ceramide + H2O
?
substrate activity assay
-
-
?
D-erythro-4-nitrobenzo-2-oxa-1,3-diazole-C12-ceramide + H2O
D-erythro-4-nitrobenzo-2-oxa-1,3-diazole-dodecanoic acid + ceramide
-
-
-
?
N-acylsphingosine + H2O
a carboxylate + sphingosine
CDase catalyzes the hydrolysis of the N-acyl linkage of ceramide to produce sphingosine
-
-
?
N-lauroylsphingosine + H2O
laurate + sphingosine
more efficient hydrolysis than of N-palmitoylsphingosine and N-stearoylsphingosine, less efficient hydrolysis than of 4-nitrobenzo-2-oxa-1,3-diazoyl-N-dodecanoylsphingosine
-
-
?
N-palmitoylsphinganine + H2O
palmitate + sphinganine
low hydrolysis rate
-
-
?
N-palmitoylsphingosine + H2O
palmitate + sphingosine
less efficient hydrolysis than of N-lauroylsphingosine, more efficient hydrolysis than of N-stearoylsphingosine
-
-
?
N-stearoylsphinganine + H2O
stearate + sphinganine
low hydrolysis rate
-
-
?
N-stearoylsphingosine + H2O
stearate + sphingosine
less efficient hydrolysis than of N-lauroylsphingosine and N-palmitoylsphingosine
-
-
?
4-nitrobenzo-2-oxa-1,3-diazoyl-N-dodecanoylsphingosine + H2O
4-nitrobenzo-2-oxa-1,3-diazoyl-dodecanoic acid + sphingosine
-
-
-
-
r
ceramide + H2O
sphingosine + a fatty acid
-
-
sphongosine is an apoptosis mediator
-
?
D-erythro-dihydrosphingosine + fatty acid
?
-
very low ceramide synthesis activity
-
-
?
D-erythro-dodecanoyl-7-nitrobenz-2-oxa-1,3-diazol-4-yl-ceramide + H2O
12-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]dodecanoic acid + sphingosine
-
-
-
-
r
D-erythro-octadecanoyl-ceramide + H2O
D-erythro-sphingosine + palmitic acid
-
mtCDase specifically hydrolyzes the D-erythro-isomer of ceramide, requirements for ceramide-enzyme interaction, ligand interaction with the enzyme occurs in a high affinity low specificity manner, in contrast to catalysis which is highly specific for D-erythro-ceramide but occurs with a lower affinity
-
-
?
D-erythro-sphingosine + fatty acid
?
-
highest ceramide synthesis activity with D-erythro-sphingosine
-
-
?
dihydro-N-myristoyl-D-erythro-sphingosine + H2O
dihydro-D-erythro-sphingosine + myristate
-
55.9% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
?
dihydro-N-palmitoyl-D-erythro-sphingosine + H2O
dihydro-D-erythro-sphingosine + palmitate
-
4.5% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
?
L-erythro-sphingosine + fatty acid
?
-
low ceramide synthesis activity
-
-
?
myristic acid + sphingosine
N-myristoylsphingosine + H2O
-
highest ceramide synthesis activity with myristic acid
-
-
?
N-acylsphingosine + H2O
carboxylate + sphingosine
the carboxylate is a fatty acid
-
-
?
N-hexanoyl-D-erythro-sphingosine + H2O
sphingosine + hexanoate
-
100.3% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
?
N-lauroyl-D-erythro-sphingosine + H2O
sphingosine + dodecanoate
-
most efficient substrate, 293.2% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
r
N-lignoceroyl-D-erythro-sphingosine + H2O
sphingosine + tetracosanoate
-
25.1% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
?
N-myristoyl-D-erythro-sphingosine + H2O
sphingosine + myristate
-
212.2% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
?
N-palmitoyl-D-erythro-sphingosine + H2O
sphingosine + palmitate
-
100% hydrolysis
-
-
r
N-stearoyl-D-erythro-sphingosine + H2O
sphingosine + stearate
-
98.5% hydrolysis compared to N-palmitoyl-D-erythro-sphingosine
-
-
?
N-acylsphingosine + H2O
a carboxylate + sphingosine
-
CDase cleaves the N-acyl linkage of ceramide into sphingosine and free fatty acid, brain CDase is able to catalyze the reverse reaction, i.e. ceramide synthesis
-
-
r
N-acylsphingosine + H2O
a carboxylate + sphingosine
-
CDase cleaves the N-acyl linkage of ceramide to produce sphingosine and free fatty acid
-
-
?
additional information
?
-
not: glycosphingolipids, e.g. GalCer, sulfatide, Galbeta(1-3)GalNAcbeta(1-4)(NeuAcalpha(2-3))Galbeta(1-4)Glcbeta(1-1)ceramide, sphingomyelin
-
-
?
additional information
?
-
ceramidase catalyzes the hydrolysis of ceramide to generate sphingosine and fatty acid, also found to catalyze the reverse reaction
-
-
?
additional information
?
-
ceramidase deacylates ceramide to form sphingosine
-
-
?
additional information
?
-
-
neutral ceramidase is involved in the regulation of ceramide-mediated signaling
-
-
?
additional information
?
-
-
no substrate in the ceramide synthesis reaction: palmitoyl-CoA
-
-
?
additional information
?
-
-
the C-terminal residues Ile-758 and Phe-756 are essential for enzyme function, the C-terminal tail is indispensable for the correct folding, localization and enzyme activity
-
-
?
additional information
?
-
-
the enzyme is important in digestion of sphingolipids
-
-
?
additional information
?
-
-
neutral ceramidase is a key enzyme for hydrolysis of sphingomyelin in the gut
-
-
?
additional information
?
-
-
long chain dihydroceramide dihydro-hexanoyl-D-erythro-sphingosine is resistant to the enzyme
-
-
?
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
ceramide + H2O
sphingosine + a fatty acid
-
-
sphongosine is an apoptosis mediator
-
?
N-acylsphingosine + H2O
carboxylate + sphingosine
the carboxylate is a fatty acid
-
-
?
additional information
?
-
ceramidase catalyzes the hydrolysis of ceramide to generate sphingosine and fatty acid, also found to catalyze the reverse reaction
-
-
?
additional information
?
-
ceramidase deacylates ceramide to form sphingosine
-
-
?
additional information
?
-
-
neutral ceramidase is involved in the regulation of ceramide-mediated signaling
-
-
?
additional information
?
-
-
the enzyme is important in digestion of sphingolipids
-
-
?
additional information
?
-
-
neutral ceramidase is a key enzyme for hydrolysis of sphingomyelin in the gut
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Zn2+
additional information
Zn2+
neutral CDase contains a zinc ion in the active site that functions as a catalytic center
additional information
112 kDa CDase from kidney is not activated by Ca2+
additional information
-
the ceramide synthesis activity is totally independent of stimulating cations
additional information
-
the enzyme is not affected by Li+, Na+, Mn2+ and Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
di-isopropyl fluorophosphate
the substrate protects against inhibition
Triton X-100
2fold activation at 0.1-0.2%, but inhibitory beyond the optimum concentration
(1R,2R)-2-(N-tetradecanoylamino)-1-(4-nitrophenyl)-1,3-propanediol
-
3-(6-phenylhexanoyl)-1,3-oxazolidin-2-one
above, pH and temperature not specified in the publication, 9.4% inhibition at 0.02 mM
3-(cyclopropylmethyl)-5-fluoro-N-hexyl-2,4-dioxopyrimidine-1-carboxamide
-
3-[4-(cyclohexyloxy)benzoyl]-1,3-oxazolidin-2-one
above, pH and temperature not specified in the publication, 18.3% inhibition at 0.02 mM
3-[6-(3-chlorophenyl)hexanoyl]-1,3-oxazolidin-2-one
above, pH and temperature not specified in the publication, 14.7% inhibition at 0.02 mM
3-[6-(4-hydroxyphenyl)hexanoyl]-1,3-oxazolidin-2-one
above, pH and temperature not specified in the publication, 4.9% inhibition at 0.02 mM
5-chloro-N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
-
5-fluoro-N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
-
5-fluoro-N-hexyl-3-(2-methylpropanoyl)-2,4-dioxopyrimidine-1-carboxamide
-
6-chloro-N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
-
cardiolipin
-
inhibits the ceramide synthesis activity: total inhibition at 2.5-5 mol%, activates the ceramidase activity, mechanism
D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol
-
inhibitor of alkaline ceramidase
D-erythro-sphingosine
-
IC50: 0.04 mol%, mt-CDase is inhibited by all stereoisomers of sphingosine with IC50 ranging from 0.04 to 0.14 mol%
D-erythro-urea-C16-ceramide
-
mtCDase, competitive inhibition, IC50: 0.33 mol%
ethyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
-
isobutyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
-
L-erythro-sphingosine
-
competitive inhibitor of ceramide synthesis activity
lysophosphatidylcholine
-
ceramide synthesis activity, 10 mol%, moderate inhibition
methyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
-
methyl 5-fluoro-3-(octylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
-
myristaldehyde
-
competitively inhibits the ceramide synthesis activity, 2.5-3 mol%, about 50% inhibition
N-hexyl-2,4-dioxo-5-(trifluoromethyl)-3,4-dihydropyrimidine-1(2H)-carboxamide
-
N-hexyl-5,6-dimethyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
-
N-hexyl-5-(4-methylpiperazin-1-yl)-2,4-dioxopyrimidine-1-carboxamide
-
N-hexyl-5-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
-
palmitaldehyde
-
ceramide synthesis activity, 2.5-3 mol%, about 50% inhibition
phosphatidic acid
-
ceramide synthesis activity, 2.5-5 mol%, total inhibition
phosphatidylcholine
-
ceramide synthesis activity, 10 mol%, moderate inhibition
phosphatidylglycerol
-
ceramide synthesis activity, 10 mol%, moderate inhibition
phosphatidylserine
-
ceramide synthesis activity, 10 mol%, moderate inhibition
2-mercaptoethanol
-
inhibits both ceramidase and ceramide synthesis activity
carmofur
a drug used in treatment of human colorectal cancers and a potent noncompetitive inhibitor in vivo active inhibitor of intracellular acid ceramidase activity
additional information
EDTA, Mn2+ and Mg2+ have little effect on activity of 112 kDa CDase from kidney
-
additional information
no inhibition by protease inhibitors such as aprotinin, PMSF, leupeptin, and pepstatin
-
additional information
-
not inhibited by N-methyl-hexadecanoyl-ceramide, 1-O-methyl-hexadecanoyl-ceramide, 3-O-methyl-hexadecanoyl-ceramide, cis-D-erythro-hexadecanoyl-ceramide, 3-O-methyl-D-erythro-sphingosine, requirements for inhibition of mtCDase
-
additional information
-
the ceramide synthesis activity is not inhibited in vitro and in cells by fuminosin B1, not inhibited by EDTA or ATP, both up to 10 mM
-
additional information
-
the enzyme is stable to trypsin and chymotrypsin exposure
-
additional information
-
GMP, GDT, GTP, TDP, TTP, UDP, and UTP, ADP and AMP have no significant effects on the enzyme activity. S-1-P has no inhibitory effect
-
additional information
synthesis and evaluation of a series of 2,4-dioxopyrimidine-1-carboxamides as acid ceramidase enzyme inhibitors, structural features of uracil derivatives that are critical for inhibition, overview. No inhibition by 7 and 27b, while 4o, 26 and 30 are unstable
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cytokine
a cytokine mixture of interleukin-1beta, tumor necrose factor-alpha and interferon-gamma is used
-
sodium cholate
112 kDa CDase from kidney, optimum concentration: 0.4-2%, 4-5fold activation
sodium taurodeoxycholate
112 kDa CDase from kidney, optimum concentration: 0.1-0.2%, 4-5fold activation
Triton X-100
2fold activation at 0.1-0.2%, but inhibitory beyond the optimum concentration
3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate
-
a bile salt analog
cardiolipin
-
activates the ceramidase activity by 2.5fold at 8-10 mol%, inhibits the ceramide synthesis activity, mechanism
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetic data for the ceramide synthesis reaction, random sequential kinetic mechanism
-
additional information
additional information
Michaelis-Menten kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00027
3-(6-phenylhexanoyl)-1,3-oxazolidin-2-one
Rattus norvegicus
above, pH and temperature not specified in the publication
0.000061
3-(cyclopropylmethyl)-5-fluoro-N-hexyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.00002
3-benzoyl-5-fluoro-N-hexyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000018
3-ethyl-5-fluoro-N-hexyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000092
3-[4-(cyclohexyloxy)benzoyl]-1,3-oxazolidin-2-one
Rattus norvegicus
above, pH and temperature not specified in the publication
0.000009
3-[6-(3-chlorophenyl)hexanoyl]-1,3-oxazolidin-2-one
Rattus norvegicus
above, pH and temperature not specified in the publication
0.000061
3-[6-(4-hydroxyphenyl)hexanoyl]-1,3-oxazolidin-2-one
Rattus norvegicus
above, pH and temperature not specified in the publication
0.0055
5-(benzyl(methyl)amino)-N-hexyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000067
5-chloro-N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000067
5-chloro-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.000733
5-ethyl-N-hexyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000029
5-fluoro-N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000021
5-fluoro-N-hexyl-3-(2-methylpropanoyl)-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000013
5-fluoro-N-hexyl-3-methyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.0000046
5-fluoro-N-octyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000012
5-trifluoromethyl-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.000029
carmofur
Rattus norvegicus
pH and temperature not specified in the publication
20
EDTA
Rattus norvegicus
-
in 50 mM Tris (pH 7.5) containing 0.3% (v/v) Triton X-100, at 37°C
0.000012
ethyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
Rattus norvegicus
pH 4.5, 37°C
1
Fe3+
Rattus norvegicus
-
in 50 mM Tris (pH 7.5) containing 0.3% (v/v) Triton X-100, at 37°C
0.000016
isobutyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
Rattus norvegicus
pH 4.5, 37°C
0.000007
methyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
Rattus norvegicus
pH 4.5, 37°C
0.000004
methyl 5-fluoro-3-(octylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate
Rattus norvegicus
pH 4.5, 37°C
0.000426
N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000012
N-hexyl-2,4-dioxo-5-(trifluoromethyl)-3,4-dihydropyrimidine-1(2H)-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000177
N-hexyl-2,4-dioxo-5-phenylpyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000426
N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.000053
N-hexyl-3-methyl-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.0014
N-hexyl-5-(4-methylpiperazin-1-yl)-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000417
N-hexyl-5-(hydroxymethyl)-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000051
N-hexyl-5-bromo-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000147
N-hexyl-5-iodo-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.0011
N-hexyl-5-methoxy-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.00146
N-hexyl-5-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.0015
N-hexyl-5-methyl-2,4-dioxo-pyrimidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.0034
N-hexyl-5-methylamino-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000875
N-hexyl-5-morpholino-2,4-dioxopyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
0.000007
N-octyl-2,4-dioxo-5-(trifluoromethyl)pyrimidine-1-carboxamide
Rattus norvegicus
pH 4.5, 37°C
5
Zn2+
Rattus norvegicus
-
in 50 mM Tris (pH 7.5) containing 0.3% (v/v) Triton X-100, at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1.91
pH 7.5, 37°C, 112 kDa CDase from kidney, hydrolysis of 4-nitrobenzo-2-oxa-1,3-diazoyl-N-dodecanoylsphingosine
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 7
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
neutral ceramidase activities both in the intestinal mucosa and content are reduced by bile diversion. The presence of bile salts is important for maintaining high intraluminal levels of neutral ceramidase
additional information
neutral ceramidase is ubiquitously expressed in various mammalian tissues
in rat hepatocytes, neutral CDase signals appear as many foci distributed throughout the cytoplasm partially co-localizing with the LPG85 signal, a marker for lysosomes/late endosomes
high CDase expression, enzyme is mainly localized at the apical membrane of proximal tubules, distal tubules and collecting ducts, enzyme is enriched in the raft microdomains with cholesterol and GM1 ganglioside
high expression level of neutral ceramidase, at the top of themicrovilli in proximal tubule cells
low CDase expression, enzyme is distributed with late endosomes/lysosomes in hepatocytes
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
113 kDa developing form, enzyme which is truncated at the C-terminus by four amino acids is retained in the endoplasmic reticulum and rapidly degraded without transportation to the Golgi apparatus
additional information
Myc-tagged CDase expressed in HEK-239 cells, a 113 kDa endoplasmic reticulum-form matures into a 133 kDa CDase during processing in the Golgi apparatus
a rat neutral CDase-GFP chimera protein, with GFP fused to the COOH terminus of the enzyme, is distributed in the ER/Golgi compartments and the plasma membrane of HEK293 cells
CDase is distributed with late endosomes/lysosomes in hepatocytes
Myc-tagged CDase expressed in HEK-239 cells, a 113 kDa endoplasmic reticulum-form matures into a 133 kDa CDase during processing in the Golgi apparatus
a rat neutral CDase-GFP chimera protein, with GFP fused to the COOH terminus of the enzyme, is distributed in the ER/Golgi compartments and the plasma membrane of HEK293 cells
CDase is distributed with late endosomes/lysosomes in hepatocytes
membrane-bound, 112 kDa-form, mainly localized at the apical membrane of proximal tubules, distal tubules and collecting ducts of kidney, microsome, sequence contains one possible transmembrane domain
membrane topology of rat neutral CDase, overview. A rat neutral CDase-GFP chimera protein, with GFP fused to the COOH terminus of the enzyme, is distributed in the ER/Golgi compartments and the plasma membrane of HEK293 cells
kidney, microsomal fraction contains a large amount of membrane-bound 112 kDa neutral CDase
-
a rat neutral CDase-GFP chimera protein, with GFP fused to the COOH terminus of the enzyme, is distributed in the ER/Golgi compartments and the plasma membrane of HEK293 cells. The CDase is transported to the plasma membrane through the classical ER/Golgi pathway
additional information
the cell-surface expression of CDase is strongly inhibited by brefeldin A or treatment at 5°C, neutral and alkaline enzyme membrane topology, overview
-
additional information
-
subcellular localization of wild-type and several C-terminal truncated CDases
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
NS-1 cell nCDase-containing exosomes block apoptosis induced by palmitate
physiological function
nCDase regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. Exosomes expressing nCDase can protect INS-1 cells or rat primary Langerhans islets against apoptosis induced by high dose cytokines
malfunction
inhibition of acid ceramidase activity sensitizes tumor cells to the effects of antineoplastic agents and radiation
physiological function
additional information
enzyme structure-function relationship, homology modeling of the enzymes using Pseudomonas CDase as the template, overview. The enzyme contains a signal/anchor sequence and a mucin box
evolution
ceramidases are classified into three distinct groups, acid (Asah1), neutral (Asah2), and alkaline (Asah3) CDases, based on their primary structure and optimum pH. Acid CDase catabolizes ceramide in lysosomes and is found only in vertebrates. In contrast, the distribution of neutral and alkaline CDases is broad, with both being found in species ranging from lower eukaryotes to mammals; however, only neutral CDase is found in prokaryotes, including some pathogenic bacteria. Neutral CDase is thought to have gained a specific domain (mucin box) in the N-terminal region after the vertebrate split, allowing the enzyme to be stably expressed at the plasmamembrane as a type II membrane protein. Molecular evolution of neutral ceramidase acquiring a mucin box, overview
evolution
distant homologues from nCDase are found in taxa all over evolution reinforcing a crucial role for ceramide
physiological function
-
synthesis of sphingosine is essential for oxidative stress-induced apoptosis of photoreceptors, pathway regulation, overview
physiological function
-
neutral ceramidase is a key participant of ceramide formation in liver mitochondria. The reverse activity of neutral ceramidase contributes to sphingolipid homeostasis in this organelle in vivo. The enzyme contributes to the overall ceramide profile of liver mitochondria at basal conditions in vivo
physiological function
acid ceramidase is a cysteine amidase that hydrolyses the proapoptotic lipid ceramide, and is abnormally high in several human tumors, which is suggestive of a role in chemoresistance. The enzyme is involved in the regulation of ceramide levels in cells and modulates the ability of this lipid messenger to influence the survival, growth and death of tumor cells
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). ASAH2_RAT
761
1
83488
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
112000
x * 112000, membrane-bound CDase from kidney, SDS-PAGE, x * 83483, CDase from kidney, sequence calculation, x * 113000, endoplasmic reticulum-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE, x * 133000, Golgi-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE
113000
x * 112000, membrane-bound CDase from kidney, SDS-PAGE, x * 83483, CDase from kidney, sequence calculation, x * 113000, endoplasmic reticulum-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE, x * 133000, Golgi-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE
133000
x * 112000, membrane-bound CDase from kidney, SDS-PAGE, x * 83483, CDase from kidney, sequence calculation, x * 113000, endoplasmic reticulum-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE, x * 133000, Golgi-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE
83483
x * 112000, membrane-bound CDase from kidney, SDS-PAGE, x * 83483, CDase from kidney, sequence calculation, x * 113000, endoplasmic reticulum-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE, x * 133000, Golgi-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE
95000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 112000, membrane-bound CDase from kidney, SDS-PAGE, x * 83483, CDase from kidney, sequence calculation, x * 113000, endoplasmic reticulum-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE, x * 133000, Golgi-form of Myc-tagged CDase expressed in HEK-239, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
112 kDa CDase from kidney, highly N-glycosylated, sequence contains 9 putative N-glycosylation sites, the N-glycosylation process is indispensable for enzyme activity
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E757R
-
mutation has no effect on activity, subcellular localization of mutant CDase expressed in HEK-293 cells
F756D
-
inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
F756I
-
mutation has little effect on activity, subcellular localization of mutant CDase expressed in HEK-293 cells
F756R
-
inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
I758D
-
inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
I758F
-
mutation decreases activity to 20% of wild-type CDase activity, subcellular localization of mutant CDase expressed in HEK-293 cells
I758R
-
inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
I758V
-
same activity as wild-type CDase, subcellular localization of mutant CDase expressed in HEK-293 cells
additional information
additional information
a rat neutral CDase-GFP chimera protein, with GFP fused to the COOH terminus of the enzyme, is distributed in the ER/Golgi compartments and the plasma membrane of HEK293 cells
additional information
-
truncation of four, but not three, amino acid residues at the C-terminus results in a complete loss of activity as well as surface expression in HEK-293 cells, the truncated enzymes are retained in the endoplasmic reticulum and rapidly degraded without transportation to the Golgi apparatus also leading to an immature/incorrect glycosylation of the protein
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
112 kDa-form from kidney: 3604fold, completely insoluble by freeze-thawing in contrast to liver CDase
native enzyme 20000fold from brain by anion exchange chromatography, affinity and hydrophobic interaction chromatography, and cation exchange chromatography, to homogeneity
native intestinal enzyme over 307fold by acetone precipitation and ion-exchange, hydrophobic-interaction chromatography, and gel filtration, to homogeneity
-
Q-Sepharose column chromatography, Superdex 200 gel filtration, heparin-Sepharose column chromatography, phenyl-Sepharose column chromatography, and Mono Q column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
112 kDa-form from kidney, expression in Escherichia coli BL21(DE3), in CHOP cells and overexpression in HEK-239 cells
DNA and amino acid determination, phylogenetic tree, recombinant expression of myc-tagged or GFP-tagged neutral CDase in HEK293 cells. When expressed in HEK293 or CHOP cells, both wild-type and mutant rat neutral CDase with a deleted mucin box are released into the medium
cloned from a brain cDNA library, stable overexpression of V5/His-tagged enzyme in HEK-293 cells
recombinant expression of V5/His-tagged enzyme using vector pEF6-V5/His in HEK-293 cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gatt, S.
Enzymatic hydrolysis of sphingolipids. I. Hydrolysis and synthesis of ceramides by an enzyme from rat brain
J. Biol. Chem.
241
3724-3730
1966
Rattus norvegicus
Bawab, S.E; Bielawska, A.; Hannun, Y.A.
Purification and characterization of a membrane-bound nonlysosomal ceramidase from rat brain
J. Biol. Chem.
274
27948-27955
1999
Rattus norvegicus
Usta, J.; El Bawab, S.; Roddy, P.; Szulc, Z.M.; Yusuf; Hannun, A.; Bielawska, A.
Structural requirements of ceramide and sphingosine based inhibitors of mitochondrial ceramidase
Biochemistry
40
9657-9668
2001
Rattus norvegicus
El Bawab, S.; Birbes, H.; Roddy, P.; Szulc, Z.M.; Bielawska, A.; Hannun, Y.A.
Biochemical characterization of the reverse activity of rat brain ceramidase. A CoA-independent and fumonisin B1-insensitive ceramide synthase
J. Biol. Chem.
276
16758-16766
2001
Rattus norvegicus
Mitsutake, S.; Tani, M.; Okino, N.; Mori, K.; Ichinose, S.; Omori, A.; Iida, H.; Nakamura, T.; Ito, M.
Purification, characterization, molecular cloning, and subcellular distribution of neutral ceramidase of rat kidney
J. Biol. Chem.
276
26249-26259
2001
Rattus norvegicus (Q91XT9)
Tani, M.; Okino, N.; Sueyoshi, N.; Ito, M.
Conserved amino acid residues in the COOH-terminal tail are indispensable for the correct folding and localization and enzyme activity of neutral ceramidase
J. Biol. Chem.
279
29351-29358
2004
Pseudomonas aeruginosa, Rattus norvegicus
Olsson, M.; Duan, R.D.; Ohlsson, L.; Nilsson, A.
Rat intestinal ceramidase: purification, properties, and physiological relevance
Am. J. Physiol. Gastrointest. Liver Physiol.
287
G929-G937
2004
Rattus norvegicus
Galadari, S.; Wu, B.X.; Mao, C.; Roddy, P.; El Bawab, S.; Hannun, Y.A.
Identification of a novel amidase motif in neutral ceramidase
Biochem. J.
393
687-695
2006
no activity in Saccharomyces cerevisiae, Rattus norvegicus (Q91XT9), Homo sapiens (Q9NR71), Homo sapiens
Duan, R.D.; Verkade, H.J.; Cheng, Y.; Havinga, R.; Nilsson, A.
Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase
Biochim. Biophys. Acta
1771
196-201
2007
Rattus norvegicus
Zhu, Q.; Jin, J.F.; Shan, X.H.; Liu, C.P.; Mao, X.D.; Xu, K.F.; Liu, C.
Chronic activation of neutral ceramidase protects beta-cells against cytokine-induced apoptosis
Acta Pharmacol. Sin.
29
593-599
2008
Rattus norvegicus (Q91XT9)
Inoue, T.; Okino, N.; Kakuta, Y.; Hijikata, A.; Okano, H.; Goda, H.M.; Tani, M.; Sueyoshi, N.; Kambayashi, K.; Matsumura, H.; Kai, Y.; Ito, M.
Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase
J. Biol. Chem.
284
9566-9577
2009
Rattus norvegicus (Q91XT9), Pseudomonas aeruginosa (Q9I596), Pseudomonas aeruginosa
Abrahan, C.E.; Miranda, G.E.; Agnolazza, D.L.; Politi, L.E.; Rotstein, N.P.
Synthesis of sphingosine is essential for oxidative stress-induced apoptosis of photoreceptors
Invest. Ophthalmol. Vis. Sci.
51
1171-1180
2010
Rattus norvegicus
Novgorodov, S.A.; Wu, B.X.; Gudz, T.I.; Bielawski, J.; Ovchinnikova, T.V.; Hannun, Y.A.; Obeid, L.M.
Novel pathway of ceramide production in mitochondria: thioesterase and neutral ceramidase produce ceramide from sphingosine and acyl-CoA
J. Biol. Chem.
286
25352-25362
2011
Mus musculus, Rattus norvegicus
Thayyullathil, F.; Chathoth, S.; Hago, A.; Patel, M.; Szulc, Z.M.; Hannun, Y.; Galadari, S.
Purification and characterization of a second type of neutral ceramidase from rat brain: a second more hydrophobic form of rat brain ceramidase
Biochim. Biophys. Acta
1811
242-252
2011
Rattus norvegicus
Ito, M.; Okino, N.; Tani, M.
New insight into the structure, reaction mechanism, and biological functions of neutral ceramidase
Biochim. Biophys. Acta
1841
682-691
2014
Dictyostelium discoideum, Mycobacterium tuberculosis, Oryza sativa, Pseudomonas aeruginosa, Tribolium castaneum, Dermatophilus congolensis, Triticum aestivum (A9YFM2), Aspergillus oryzae (Q5B5D5), Danio rerio (Q5W7F1), Rattus norvegicus (Q91XT9), Mus musculus (Q9JHE3), Homo sapiens (Q9NR71), Drosophila melanogaster (Q9VA70), Laodelphax striatellus (R4N4U2)
Pizzirani, D.; Pagliuca, C.; Realini, N.; Branduardi, D.; Bottegoni, G.; Mor, M.; Bertozzi, F.; Scarpelli, R.; Piomelli, D.; Bandiera, T.
Discovery of a new class of highly potent inhibitors of acid ceramidase: synthesis and structure-activity relationship (SAR)
J. Med. Chem.
56
3518-3530
2013
Rattus norvegicus (Q6P7S1)
Realini, N.; Solorzano, C.; Pagliuca, C.; Pizzirani, D.; Armirotti, A.; Luciani, R.; Costi, M.P.; Bandiera, T.; Piomelli, D.
Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity
Sci. Rep.
3
1035
2013
Homo sapiens (Q13510), Homo sapiens, Rattus norvegicus (Q6P7S1)
Coant, N.; Hannun, Y.A.
Neutral ceramidase advances in mechanisms, cell regulation, and roles in cancer
Adv. Biol. Regul.
71
141-146
2019
Nilaparvata lugens, Amorphophallus muelleri (A0A2D1WBF2), Rattus norvegicus (Q91XT9), Mus musculus (Q9JHE3), Homo sapiens (Q9NR71)
Li, Y.; Chen, Q.; Yang, L.; Li, Y.; Zhang, Y.; Qiu, Y.; Ren, J.; Lu, C.
Identification of highly potent N-acylethanolamine acid amidase (NAAA) inhibitors optimization of the terminal phenyl moiety of oxazolidone derivatives
Eur. J. Med. Chem.
139
214-221
2017
Rattus norvegicus (Q6P7S1)
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