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Literature summary extracted from

  • Rodriguez-Cuenca, S.; Barbarroja, N.; Vidal-Puig, A.
    Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity (2015), Biochim. Biophys. Acta, 1851, 40-50 .
    View publication on PubMed

Protein Variants

EC Number Protein Variants Comment Organism
1.14.19.17 L175Q naturally occuring mutation, the mutation is is associated with increased levels of dihydroceramides, decreased levels of cholesterol esters and decreased waist to hip ratio Homo sapiens
1.14.19.17 additional information generation of DEGS1 knockout mice Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.19.17 celecoxib
-
Homo sapiens
1.14.19.17 curcumin
-
Homo sapiens
1.14.19.17 DELTA9-tetrahydrocannabinol
-
Homo sapiens
1.14.19.17 fenretinide i.e. N-(4-hydroxyphenyl) retinamide, fenretinide directly targets and irreversibly inhibits DEGS1 in a time-dependent manner, by disrupting the electron transport necessary for desaturation Homo sapiens
1.14.19.17 GT11 a cyclopropenylceramide (C8CCP) that acts in primary neuronal cultures as a potent specific and competitive inhibitor of DESG1 at concentrations up to 0.001 mM Homo sapiens
1.14.19.17 resveratrol
-
Homo sapiens
1.14.19.17 XM462
-
Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.14.19.17 endoplasmic reticulum
-
Homo sapiens 5783
-
1.14.19.17 endoplasmic reticulum
-
Mus musculus 5783
-
1.14.19.17 endoplasmic reticulum
-
Drosophila melanogaster 5783
-
1.14.19.17 endoplasmic reticulum N-myristoylation targets DEGS1 from the endoplasmic reticulum to the mitochondrial outer membrane, the effect is specific for myristic acid Chlorocebus aethiops 5783
-
1.14.19.17 mitochondrial outer membrane N-myristoylation targets DEGS1 from the endoplasmic reticulum to the mitochondrial outer membrane, the effect is specific for myristic acid Chlorocebus aethiops 5741
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ Chlorocebus aethiops
-
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ Homo sapiens
-
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ Mus musculus
-
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ Drosophila melanogaster
-
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.14.19.17 Chlorocebus aethiops
-
-
-
1.14.19.17 Drosophila melanogaster Q94515
-
-
1.14.19.17 Homo sapiens O15121
-
-
1.14.19.17 Mus musculus O09005
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
1.14.19.17 lipoprotein N-myristoylation targets DEGS1 from the endoplasmic reticulum to the mitochondrial outer membrane and increases its activity leading to an excess of ceramides and subsequent apoptosis in COS-7 cells, the effect is specific for myristic acid Chlorocebus aethiops

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.19.17 adipose tissue
-
Homo sapiens
-
1.14.19.17 breast cancer cell
-
Homo sapiens
-
1.14.19.17 C2C12 cell
-
Mus musculus
-
1.14.19.17 COS-7 cell
-
Chlorocebus aethiops
-
1.14.19.17 fat body
-
Drosophila melanogaster
-
1.14.19.17 liver
-
Homo sapiens
-
1.14.19.17 MCF-7 cell
-
Homo sapiens
-
1.14.19.17 Mueller glial cell
-
Homo sapiens
-
1.14.19.17 muscle
-
Homo sapiens
-
1.14.19.17 neuronal cell primary Homo sapiens
-
1.14.19.17 retina
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
-
Chlorocebus aethiops a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
-
Homo sapiens a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
-
Mus musculus a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?
1.14.19.17 a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
-
Drosophila melanogaster a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
?

Synonyms

EC Number Synonyms Comment Organism
1.14.19.17 Degs1
-
Chlorocebus aethiops
1.14.19.17 Degs1
-
Homo sapiens
1.14.19.17 Degs1
-
Mus musculus
1.14.19.17 Degs1
-
Drosophila melanogaster
1.14.19.17 DES-1
-
Drosophila melanogaster
1.14.19.17 DES1
-
Chlorocebus aethiops
1.14.19.17 DES1
-
Homo sapiens
1.14.19.17 DES1
-
Mus musculus
1.14.19.17 DES1
-
Drosophila melanogaster
1.14.19.17 dihydroceramide desaturase
-
Chlorocebus aethiops
1.14.19.17 dihydroceramide desaturase
-
Homo sapiens
1.14.19.17 dihydroceramide desaturase
-
Mus musculus
1.14.19.17 dihydroceramide desaturase
-
Drosophila melanogaster
1.14.19.17 ifc
-
Drosophila melanogaster

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.19.17 cytochrome b5
-
Chlorocebus aethiops
1.14.19.17 cytochrome b5
-
Homo sapiens
1.14.19.17 cytochrome b5
-
Mus musculus
1.14.19.17 cytochrome b5
-
Drosophila melanogaster
1.14.19.17 NAD(P)H Des1 requires NADPH or NADH as electron donor and oxygen as electron acceptor Homo sapiens

Expression

EC Number Organism Comment Expression
1.14.19.17 Homo sapiens natural forms of vitamin E can induce dihydroceramide levels by repressing DEGS1 activity. Adiponectin represses the expression of degs1 in MCF-7 cells down
1.14.19.17 Homo sapiens interferon gamma upregulates expression levels of DEGS1 in the human mononuclear cell line THP-1, similarly, interleukin 2 increases expression levels of DEGS1 in human natural killer cells. all trans-Retinoic acid increases the enzyme expression up
1.14.19.17 Mus musculus palmitate induces the expression of DEGS1 leading to an associated increase in ceramide levels. Increased levels of palmitate may enhance the synthesis of ceramides by increasing the flux of palmitate substrate and expression rates of DEGS1. Monounsaturated fatty acids, including oleate, are able to attenuate the induction elicited by palmitate and prevent ceramide production up

General Information

EC Number General Information Comment Organism
1.14.19.17 malfunction DEGS1 ablation induces fat body cell hypertrophy, increased fat body lipid droplet size, and increased abdominal adiposity. In flies, genetic ablation of ifc gene (orthologue for degs1) causes an obese phenotype (larger fat bodies) independent of the caloric intake Drosophila melanogaster
1.14.19.17 malfunction DEGS1 inhibition enhances insulin sensitivity, DEGS1 ablation induces autophagy and blocks cellular proliferation, and provides protection from chemotherapeutic agents through the activation of prosurvival pathways. Homozygous DEGS1 knockout mouse exhibits a severe phenotype characterised by low survival rate and multiple abnormalities. The heterozygous mice are viable with normal birth Mendelian rates, superficial biochemical phenotypical analysis reveals that mutant degs1 hets mice show higher DhCer/Cer ratios in multiple organs. This is associated with enhanced insulin sensitivity, normal glucose tolerance and resistance to dexamethasone induced insulin resistance. Embryonic fibroblasts from DEGS1knockout mice show enhanced AKT signalling, likely due to the absence of ceramides and not a result of the direct effect of dihydroceramide accumulation. DEGS1 heterozygotes gain more weight over time in comparison to wild-type mice Mus musculus
1.14.19.17 malfunction DESG1 inhibition block the cell growth, cell migration, cytoskeleton modification, response to insulin, impair of endomembrane trafficking. Fenretinide can exert part of its insulin sensitising effects in liver and muscle by inhibiting DEGS1 and hence decreasing the synthesis of ceramides with the concomitant increase in diydroceramide levels Homo sapiens
1.14.19.17 malfunction increased DEGS1 activation through myristoylation induces apoptosis mediated by the increase of ceramides Chlorocebus aethiops
1.14.19.17 metabolism the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides Chlorocebus aethiops
1.14.19.17 metabolism the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides Homo sapiens
1.14.19.17 metabolism the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides Mus musculus
1.14.19.17 metabolism the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides Drosophila melanogaster
1.14.19.17 physiological function enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. DEGS1 is required for the condensation of chromatin (essential in the initiation of the meiosis in the spermatogenesis). Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview Drosophila melanogaster
1.14.19.17 physiological function enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. DEGS1 mediates the adaptation to chronic hypoxia and is involved in the induction of insulin resistance mediated by palmitate. Role of fatty acids as modulators of DEGS1 activity and ceramide synthesis. DEGS1 may have a part in fatty acid induced insulin resistance and apoptosis. Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview Mus musculus
1.14.19.17 physiological function enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. DESG1 acts as a vitamin A isomerase in Muller glial cells of the retina. DEGS1 acts as oxygen biosensor. It is involved in the inflammation signalling initiated by interferon gamma and in the inflammation signalling mediated by interleukin-2, IL-2. DEGS1 may play a role in controlling and participating in the levels of ceramides normally associated to inflammation processes. Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview. Dihydroceramides correlate better than ceramides with body mass index (BMI) and waist circumference in cohorts of overweight-obese subjects Homo sapiens
1.14.19.17 physiological function enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. Increased DEGS1 activation through myristoylation induces apoptosis mediated by the increase of ceramides. Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview Chlorocebus aethiops