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Literature summary extracted from

  • 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 (2009), Biochim. Biophys. Acta, 1793, 1218-1227 .
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.3.1.299 cisplatin
-
 Homo sapiens
2.3.1.299 dithiothreitol
-
 Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.24 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 Mus musculus
2.3.1.299 gene CERS1, ectopic expression of N-terminally FLAG3-tagged CerS1 in HEK-293 or HeLa cells, recombinant expression of enzyme mutant H182A/H183A Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.24 additional information in HEK-293 cells, ectopically expressed murine CerS5 only sensitized cells to doxorubicin and vincristine Mus musculus
2.3.1.299 H182A/H183A site-directed mutagenesis Mus musculus
2.3.1.299 H182A/H183A the mutant shows greatly reduced activity compared to the wild type enzyme Homo sapiens
2.3.1.299 additional information in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, CerS1 proteasomal degradation is ubiquitin mediated. The turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. Recombinantly expressed murine isozyme CerS1 sensitizes cells to a wide range of drugs including cisplatin, carboplatin, doxorubicin and vincristine, incontrast to isozymes CerS4 and CerS5. The specific effect of CerS1 is mediated through the activation of the MAP kinase p38 Mus musculus
2.3.1.299 additional information in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. Recombinant isozyme CerS1 sensitizes cells to a wide range of drugs including cisplatin, carboplatin, doxorubicin and vincristine, in contrast to isozymes CerS4 and CerS5. The specific effect of CerS1 is mediated through the activation of the MAP kinase p38 Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.299 MG132
-
 Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.1.24 Mg2+ activates Mus musculus
2.3.1.299 Mg2+ activates Mus musculus
2.3.1.299 Mg2+ activates Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.24 sphinganine + palmitoyl-CoA Mus musculus
-
 N-palmitoylsphinganine + CoA
-
 ?
2.3.1.299 sphinganine + stearoyl-CoA Mus musculus
-
 N-stearoylsphinganine + CoA
-
 ?
2.3.1.299 sphinganine + stearoyl-CoA Homo sapiens
-
 N-stearoylsphinganine + CoA
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.24 Mus musculus Q9D6K9
-
-
2.3.1.299 Homo sapiens
-
-
-
2.3.1.299 Homo sapiens P27544
-
-
2.3.1.299 Mus musculus P27545
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.3.1.299 phosphoprotein CerS1 is phosphorylated in vivo and activation of protein kinase C increases the phosphorylation of the protein Mus musculus
2.3.1.299 phosphoprotein CerS1 is phosphorylated in vivo and activation of protein kinase C increases the phosphorylation of the protein Homo sapiens
2.3.1.299 phosphoprotein the enzyme turnover is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC). p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. The enzyme is phosphorylated in vivo and activation of PKC increases the phosphorylation of the protein Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.299 A-549 cell
-
 Homo sapiens
-
2.3.1.299 HEK-293 cell
-
 Homo sapiens
-
2.3.1.299 HeLa cell
-
 Homo sapiens
-
2.3.1.299 U-373MG cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.24 sphinganine + palmitoyl-CoA
-
 Mus musculus N-palmitoylsphinganine + CoA
-
 ?
2.3.1.299 sphinganine + stearoyl-CoA
-
 Mus musculus N-stearoylsphinganine + CoA
-
 ?
2.3.1.299 sphinganine + stearoyl-CoA
-
 Homo sapiens N-stearoylsphinganine + CoA
-
 ?
2.3.1.299 stearoyl-CoA + sphinganine
-
 Homo sapiens N-(stearoyl)-sphinganine + CoA
-
 ?

Subunits

EC Number Subunits Comment Organism
2.3.1.24 ? x * 50000, recombinant FLAG3-tagged CerS5, SDS-PAGE Mus musculus
2.3.1.299 ? x * 39000, FLAG-tagged enzyme, SDS-PAGE Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.3.1.24 ceramide synthase 5
-
 Mus musculus
2.3.1.24 CerS5
-
 Mus musculus
2.3.1.299 ceramide synthase 1
-
 Homo sapiens
2.3.1.299 ceramide synthase 1
-
 Mus musculus
2.3.1.299 CerS1
-
 Homo sapiens
2.3.1.299 CerS1
-
 Mus musculus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.24 37
-
 assay at Mus musculus
2.3.1.299 37
-
 assay at Mus musculus
2.3.1.299 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.24 7.5
-
 assay at Mus musculus
2.3.1.299 7.5
-
 assay at Mus musculus
2.3.1.299 7.5
-
 assay at Homo sapiens

Expression

EC Number Organism Comment Expression
2.3.1.299 Mus musculus diverse stresses including chemotherapeutic drugs, UV light and DTT can induce CerS1 turnover up
2.3.1.299 Homo sapiens diverse stresses including chemotherapeutic drugs, UV light and DTT can induce CerS1 turnover up

General Information

EC Number General Information Comment Organism
2.3.1.24 physiological function isozyme CerS5 sensitizes cells to doxorubicin and vincristine Mus musculus
2.3.1.299 metabolism in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover Mus musculus
2.3.1.299 metabolism in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover Homo sapiens
2.3.1.299 physiological function ceramide synthase 1 (CerS1) is the most structurally and functionally distinct from the other CerS enzymes, the enzyme is regulated via a regulatory mechanism that specifically controls the level of CerS1 via ubiquitination and proteasome dependent protein turnover Mus musculus
2.3.1.299 physiological function ceramide synthase 1 (CerS1) is the most structurally and functionally distinct from the other CerS enzymes, the enzyme is regulated via a regulatory mechanism that specifically controls the level of CerS1 via ubiquitination and proteasome dependent protein turnover Homo sapiens