3.5.1.23: ceramidase
This is an abbreviated version!
For detailed information about ceramidase, go to the full flat file.
Word Map on EC 3.5.1.23
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3.5.1.23
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adipor1
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sphingolipids
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obesity
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adipokine
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agonist
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sphingomyelinase
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sphingomyelin
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lysosomal
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farber
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obese
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leptin
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adipocytes
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amp-activated
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sphingosine-1-phosphate
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peroxisome
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cardiovascular
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proliferator-activated
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triglyceride
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globular
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insulin-sensitizing
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high-fat
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tnf
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smases
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adipocytokine
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adipocyte-derived
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monophosphate-activated
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anti-atherogenic
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t-cadherin
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steatosis
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adiposity
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glucosylceramide
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glycosphingolipids
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obesity-related
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antidiabetic
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1-phosphate
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seven-transmembrane
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gaucher
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dihydrosphingosine
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p-ampk
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palmitoyltransferase
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homa-ir
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sphingoid
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hoarseness
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ceramide-induced
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sphinganine
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ceramide-mediated
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dihydroceramide
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myoclonic
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adipocyte-secreted
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analysis
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pharmacology
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drug development
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medicine
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hypoadiponectinemia
- 3.5.1.23
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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
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p-ampk
- palmitoyltransferase
-
homa-ir
-
sphingoid
- hoarseness
-
ceramide-induced
- sphinganine
-
ceramide-mediated
- dihydroceramide
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myoclonic
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adipocyte-secreted
- analysis
- pharmacology
- drug development
- medicine
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hypoadiponectinemia
Reaction
Synonyms
(dihydro)ceramidase, AC, aCDase, ACER, ACER type 3, ACER-2, ACER1, ACER2, ACER3, acid ceramidase, acylsphingosine deacylase, adiponectin receptor, ADIPOR2, alkaline ceramidase, alkaline ceramidase 1, alkaline ceramidase 2, alkaline ceramidase 3, alkCDase, alkCDase-1, alkCDase-2, ASAH-1, ASAH1, asah1b, ASAH2, ASAH2B, ASAH3, AsahA, AtACER, AtNCER1, bwa, CBCDase, CDase, CDase II, CER2, ceramidase, Dacer, Drosophila alkaline ceramidase, glycosphingolipid ceramide deacylase, Golgi alkaline ceramidase, haCER1, intramembrane ceramidase, LsnCer, maCER1, mt-CDase, N-acylsphingosine amidohydrolase, N-acylsphingosine amidohydrolase 2, N-acylsphingosine amidohydrolase-1, N-acylsphingosine aminohydrolase, N-acylsphingosine deacylase, N-CDase, nCDase, ncer1, neutral CDase, neutral ceramidase, neutral ceramidase 2, NlnCDase, OsCDase, PaCD, PaCDase, pan-ceramidase, PHP32, phytoalkaline ceramidase, phytoCDase, Putative 32 KDA heart protein, SCDase, sphingolipid ceramide N-deacylase, Tncer, TOD1, turgor regulation defect 1, Ydc1p, yeast dihydroceramidase 1, yeast phyto-ceramidase 1, Ypc1p, znCD
ECTree
3.5.1.23 ceramidaseAdvanced search results
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results (Engineering
Engineering on EC 3.5.1.23 - ceramidase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D331N
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
E138V
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
E180K
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
E33G
naturally occuring inactive mutant, the mutation results in the destabilization of the calcium binding site
F136L
naturally occuring disease mutation, F136 is located near the lipid tails of the modeled substrate and at the alpha-beta interface, the F136L mutation can destabilize the heterodimer and substrate interactions, affects the hydrophobic surface of the protein
F328Q/F329Q/L330Q
site-directed mutagenesis, hydrophobic patches mutated near the substrate binding channel, the mutant shows reduced ceramide hydrolysis compared with wild-type in the liposomal assay
F87Q/V88Q/V93Q
site-directed mutagenesis, mutation of a site further from the substrate-binding site, the mutant shows reduced ceramide hydrolysis compared with wild-type in the liposomal assay
G168W
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
G235D
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
G235R
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
L182V
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
L80Q/V165Q/L167Q
site-directed mutagenesis, hydrophobic patches mutated near the substrate binding channel, the mutant shows reduced ceramide hydrolysis compared with wild-type in the liposomal assay
N320D
N320S
N320X
naturally occuring disease mutation, active site residue mutation, inhibits autocleavage and/or substrate hydrolysis
P362R
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
P362T
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
R226P
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
R254G
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
R333G
naturally occuring disease mutation, active site residue mutation, that hinders the R333 function, affects the activation of the proenzyme
R333H
naturally occuring disease mutation, active site residue mutation, that hinders the R333 function, affects the activation of the proenzyme
R333X
naturally occuring disease mutation, active site residue mutation, inhibits autocleavage and/or substrate hydrolysis
S258A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
S354A
S374A
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S396A
site-directed mutagenesis, the mutant shows slightly reduced activity compared to the wild-type enzyme
S595A
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S729A
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T179I
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
T222K
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
T42A
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
T42M
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
V97D
naturally occuring disease mutation, the mutation inhibit the interaction of aCDase with negatively charged liposomes
V97E
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
V97G
naturally occuring disease mutation, the mutation likely destabilizes helix-alpha2 in the alpha-subunit in which it resides
W169Q/I171Q/W176Q
site-directed mutagenesis, mutation of the L4-6 loop in the beta-subunit, the mutant shows reduced ceramide hydrolysis compared with wild-type in the liposomal assay
W169R
naturally occuring disease mutation, the mutation affects the hydrophobic surface of the protein
Y36C
naturally occuring disease mutation, the mutation is predicted to affect the folding or stability of the protein
H97A/H99A
mutant, Zn2+-binding site and deprotonation site mutated
E757R
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mutation has no effect on activity, subcellular localization of mutant CDase expressed in HEK-293 cells
F756D
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inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
F756I
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mutation has little effect on activity, subcellular localization of mutant CDase expressed in HEK-293 cells
F756R
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inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
I758D
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inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
I758F
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mutation decreases activity to 20% of wild-type CDase activity, subcellular localization of mutant CDase expressed in HEK-293 cells
I758R
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inactive mutant, subcellular localization of mutant CDase expressed in HEK-293 cells
I758V
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same activity as wild-type CDase, subcellular localization of mutant CDase expressed in HEK-293 cells
additional information
N320D
naturally occuring disease mutation, active site residue mutation, disrupts the functional requirement for an asparagine side chain at this position
N320D
naturally occuring disease mutation, affects the activation of the proenzyme
N320S
naturally occuring disease mutation, active site residue mutation, disrupts the functional requirement for an asparagine side chain at this position
N320S
naturally occuring disease mutation, affects the activation of the proenzyme
additional information
construction of an acer-1 T-DNA insertion mutant, the acer-1 allele has a T-DNA insertion in the 50 untranslated region (5'-UTR) of AtACER, phenotype with reduced stature, with smaller, narrower, glossier leaves and smaller flowers than wild-type plants, sphingolipid profiles in acer-1, overview. The AtACER transgene can complement the phenotypes of the acer-1 mutant
additional information
construction of T-DNA insertion mutants harboring the mutation in exn tod1-1 or tod1-2
additional information
the Arabidopsis thaliana neutral ceramidase DNA insertion mutant ncer1 has no visible phenotype, but accumulates hydroxyceramides, and shows increased sensitivity to oxidative stress induced by methyl viologen. Plants overexpressing AtNCER1 show increased tolerance to oxidative stress. Neutral ceramidase mutants have increased sensitivity to C2-ceramide induced cell death
additional information
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the Arabidopsis thaliana neutral ceramidase DNA insertion mutant ncer1 has no visible phenotype, but accumulates hydroxyceramides, and shows increased sensitivity to oxidative stress induced by methyl viologen. Plants overexpressing AtNCER1 show increased tolerance to oxidative stress. Neutral ceramidase mutants have increased sensitivity to C2-ceramide induced cell death
additional information
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the Arabidopsis thaliana neutral ceramidase DNA insertion mutant ncer1 has no visible phenotype, but accumulates hydroxyceramides, and shows increased sensitivity to oxidative stress induced by methyl viologen. Plants overexpressing AtNCER1 show increased tolerance to oxidative stress. Neutral ceramidase mutants have increased sensitivity to C2-ceramide induced cell death
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additional information
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construction of T-DNA insertion mutants harboring the mutation in exn tod1-1 or tod1-2
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additional information
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enzyme knockout, via antisense construct using three different antisense morpholino oligonucleotides (AMOs 1, 2, and 3) that are designed based on sequences at different sites of the 5'-untranslated region, leads to an increase in the number of zebrafish embryos with severe morphological qand cellular abnormalities such as abnormal morphogenesis inhead and tail, pericardiac edema, defect of blood cell circulation, and an increase in apoptotic cells, phenotype, overview
additional information
insertional mutagenesis leading to enzyme inactivation, transposon location of the dacer mutant, overview. The mutation increases the levels of ceamides in both the pupal and adult stages, and increases pre-adult development time, lifespan, and anti-oxidative stress capacity, overview
additional information
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insertional mutagenesis leading to enzyme inactivation, transposon location of the dacer mutant, overview. The mutation increases the levels of ceamides in both the pupal and adult stages, and increases pre-adult development time, lifespan, and anti-oxidative stress capacity, overview
additional information
targeted expression of neutral CDase can rescue retinal degeneration in a subset of Drosophila phototransduction mutants
additional information
generation of a Dacer-deficient Drosophila melanogaster mutant, which has higher catalase (CAT) activity and CAT transcription level, leading to higher resistance to oxidative stress induced by paraquat, quantitative proteomic analysis of wild-type and mutant cells. Three oxidoreductases, including two cytochrome P450 (CG3050, CG9438) and an oxoglutarate/iron-dependent dioxygenase (CG17807), are most significantly upregulated in the Dacer overexpressing mutant. Altered antioxidative activity in Dacer mutant might be responsible for increased oxidative stress resistance
additional information
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generation of a Dacer-deficient Drosophila melanogaster mutant, which has higher catalase (CAT) activity and CAT transcription level, leading to higher resistance to oxidative stress induced by paraquat, quantitative proteomic analysis of wild-type and mutant cells. Three oxidoreductases, including two cytochrome P450 (CG3050, CG9438) and an oxoglutarate/iron-dependent dioxygenase (CG17807), are most significantly upregulated in the Dacer overexpressing mutant. Altered antioxidative activity in Dacer mutant might be responsible for increased oxidative stress resistance
additional information
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insertional mutagenesis leading to enzyme inactivation, transposon location of the dacer mutant, overview. The mutation increases the levels of ceamides in both the pupal and adult stages, and increases pre-adult development time, lifespan, and anti-oxidative stress capacity, overview
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additional information
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blocking of acid ceramidase but not sphingosine kinase activity in alveolar macrophages leads to decreased ERK and Akt activity and induction of cell death, sphingosine and L-threo-dihydrosphingosine reverse the antisurvival effects of acid ceramidase inhibition in alveolar macrophages
additional information
high ectopic expression of haCER2 causes fragmentation of the Golgi complex and growth arrest in HeLa cells due to sphingosine accumulation, low ectopic expression increases sphingosine 1-phosphate level without sphingosine accumulation, promoting cell proliferation in serum-free medium, this proliferative effect is suppressed by dimethylsphingosine, an inhibitor of the S1P formation, or by RNAi -mediated inhibition of S1P1, a G-protein-coupled receptor for S1P, the RNAi-mediated down-regulation of haCER2 enhances the serum deprivation-induced growth arrest and apoptosis of HeLa cells, which is inhibited by addition of exogenous S1P, serum deprivation up-regulates both haCER2 mRNA and activity in recombinant HeLa cells, haCER2mRNA is also up-regulated in some tumors, overview
additional information
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high ectopic expression of haCER2 causes fragmentation of the Golgi complex and growth arrest in HeLa cells due to sphingosine accumulation, low ectopic expression increases sphingosine 1-phosphate level without sphingosine accumulation, promoting cell proliferation in serum-free medium, this proliferative effect is suppressed by dimethylsphingosine, an inhibitor of the S1P formation, or by RNAi -mediated inhibition of S1P1, a G-protein-coupled receptor for S1P, the RNAi-mediated down-regulation of haCER2 enhances the serum deprivation-induced growth arrest and apoptosis of HeLa cells, which is inhibited by addition of exogenous S1P, serum deprivation up-regulates both haCER2 mRNA and activity in recombinant HeLa cells, haCER2mRNA is also up-regulated in some tumors, overview
additional information
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no accumulation of diacylglycerol occurs due to overexpression of the recombinant enzyme in myoblasts, but the recombinant enzyme prevents the inhibition of insulin signaling by palmitate in C1c12 myotubes, overview
additional information
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a germ line single nucleotide polymorphism creates a splice site resulting in alternatively-spliced KLF6 isoforms, termed KLF6 SV1, SV2 and SV3. The splice variants show that SV1 has a counteracting effect on the wild-type KLF6 tumor suppressor activity, thus permitting tumor progression
additional information
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ACER2 mutant, ACER2DELTAN36, lacking the N-terminal tail, the first 36 amino acid residues, exhibits undetectable activity and is mislocalized to the endoplasmic reticulum. Overexpression of ACER2, ACER2DELTAN13, but not ACER2DELTAN36 increased the release of sphingosine 1-phosphate from cells, suggesting that its mislocalization does not affect the ability of ACER2 to regulate sphingosine 1-phosphate secretion. However, overexpression of ACER2 but not ACER2DELTAN13 or ACER2DELTAN36 inhibits the glycosylation of integrin beta1 subunit and Lamp1, suggesting that its mistargeting abolishes the ability of ACER2 to regulation protein glycosylation
additional information
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knockdown of ACER1, ACER2, and ACEr3 in K562 cells by siRNA and lentiviral shRNA transduction. Transduction with lentiviral particles expressing an ACER3-specific shRNA decreases ACER3 mRNA but increased ACER2 mRNA in K562 cells, and transduction with lentiviral particles expressing ACER2-specific shRNA decreases ACER2 mRNA but increased ACER1 mRNA and vice versa. Thus knocking down the expression of one alkaline ceramidase up-regulates another
additional information
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overexpression of ACER2 augments the 4-N-(4-hydroxyphenyl)retinamide-induced generation of dihydrosphingosine, as well as 4-N-(4-hydroxyphenyl)retinamide cytotoxicity and death in tumor cells, whereas knocking down ACER2 had the opposite effects. ACER2 overexpression or GT11, a dihydrosphingosine desaturase inhibitor, treatment alone caused little or no decrease in cell viability, whereas ACER2 overexpression along with GT11 treatment markedly decreased cell viability
additional information
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generation of a tetracycline-inducible ASAH1 short hairpin RNA H295R human adrenocortical stable cell line
additional information
generation of a tetracycline-inducible ASAH1 short hairpin RNA H295R human adrenocortical stable cell line
additional information
ASAH1 silencing by siRNA. An increase in expression in the cell cycle inhibitor p27 is observed upon MITF inhibition by siRNA, but does not occur in these cells when they are transduced with ASAH1
additional information
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ASAH1 silencing by siRNA. An increase in expression in the cell cycle inhibitor p27 is observed upon MITF inhibition by siRNA, but does not occur in these cells when they are transduced with ASAH1
additional information
ATRA downregulates nCDase expression at the message level results in less protein and activity in SH-SY5Y neuroblastoma cells
additional information
overexpression and knockdown of acid ceramidase via lentiviral transduction in HEK-293T/17 cells
additional information
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overexpression and knockdown of acid ceramidase via lentiviral transduction in HEK-293T/17 cells
additional information
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construction of disruption mutant of Asah2 by using a targeted ES clone to produce chimeras and subsequently heterozygous mice, interbreeding of the Asah2 heterozygous mice yielded wild-type, heterozygous, and homozygous mutant null offspring, Asah2 null mice are deficient in the intestinal degradation of ceramide, Asah2 null mice have a normal life span and do not show obvious abnormalities or major alterations in total ceramide levels in tissues
additional information
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RNA interference gene silencing of the neutral CDase in mouse B16 cells leading to reduced enzyme activity and reduced levels of sphingosine and sphingosine 1-phosphate
additional information
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truncation of six C-terminal amino acids, but not of five, results in complete loss of CDase activity
additional information
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construction of a CDase-null mutant via homologous recombination and gene disruption, CDase-deficient mutants lack any CDase activity, the hemolytic activity by the CDase mutants against human erythrocytes is significantly reduced compared with that by the wild-type
additional information
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construction of a CDase-null mutant via homologous recombination and gene disruption, CDase-deficient mutants lack any CDase activity, the hemolytic activity by the CDase mutants against human erythrocytes is significantly reduced compared with that by the wild-type
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additional information
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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
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
comparison of membrane topology of wild-type and mutant enzymes, overview
additional information
comparison of membrane topology of wild-type and mutant enzymes, overview
additional information
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comparison of membrane topology of wild-type and mutant enzymes, overview
