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Literature summary for 2.3.1.297 extracted from

  • Pewzner-Jung, Y.; Brenner, O.; Braun, S.; Laviad, E.L.; Ben-Dor, S.; Feldmesser, E.; Horn-Saban, S.; Amann-Zalcenstein, D.; Raanan, C.; Berkutzki, T.; Erez-Roman, R.; Ben-David, O.; Levy, M.; Holzman, D.; Park, H.; Nyska, A.; Merrill, A.H.; Futerman, A.H.
    A critical role for ceramide synthase 2 in liver homeostasis II. insights into molecular changes leading to hepatopathy (2010), J. Biol. Chem., 285, 10911-10923 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene CERS2, genotyping, quantitative PCR enzyme expression analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information CerS2 null mouse generation from embryonic stem cells harboring a gene trap (GT) retroviral vector insertion in the first intron of the CerS2 gene, and characterization of the changes in the long chain base and sphingolipid composition of livers from these mice. Ceramide and downstream sphingolipids are devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. C16-ceramide levels are elevated, and as a result, total ceramide levels are unaltered. C16-ceramide synthesis in vitro is not increased. Levels of sphinganine are significantly elevated by up to 50fold, reminiscent of the effect of the ceramide synthase inhibitor fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways are significantly changed. Total glycerophospholipid and cholesterol levels are unaltered, although there is a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
fumonisin B1
-
Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane liver microsomal membranes from CerS2 null mice display higher membrane fluidity and show morphological changes. Membrane morphology is studied by fluorescence microscopy, overview Mus musculus 16020
-
microsome
-
Mus musculus
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
D-erythro-sphinganine + behenoyl-CoA Mus musculus
-
N-behenoyl-D-sphinganine + CoA
-
?
D-erythro-sphinganine + lignoceroyl-CoA Mus musculus
-
N-lignoceroyl-D-sphinganine + CoA
-
?
D-erythro-sphinganine + nervonoyl-CoA Mus musculus
-
N-nervonoyl-D-sphinganine + CoA
-
?
sphinganine + cerotoyl-CoA Mus musculus low activity N-cerotoylsphinganine + CoA
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q924Z4
-
-

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-erythro-sphinganine + behenoyl-CoA
-
Mus musculus N-behenoyl-D-sphinganine + CoA
-
?
D-erythro-sphinganine + behenoyl-CoA preferred substrate Mus musculus N-behenoyl-D-sphinganine + CoA
-
?
D-erythro-sphinganine + lignoceroyl-CoA
-
Mus musculus N-lignoceroyl-D-sphinganine + CoA
-
?
D-erythro-sphinganine + lignoceroyl-CoA preferred substrate Mus musculus N-lignoceroyl-D-sphinganine + CoA
-
?
D-erythro-sphinganine + nervonoyl-CoA
-
Mus musculus N-nervonoyl-D-sphinganine + CoA
-
?
additional information CerS2 can utilize a wider range of fatty acyl-CoAs but uses mainly C22 to C24 Mus musculus ?
-
?
sphinganine + cerotoyl-CoA low activity Mus musculus N-cerotoylsphinganine + CoA
-
?

Synonyms

Synonyms Comment Organism
ceramide synthase 2
-
Mus musculus
CerS2
-
Mus musculus

General Information

General Information Comment Organism
malfunction CerS2 null mouse show ceramide and downstream sphingolipids devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. C16-ceramide levels are elevated, and as a result, total ceramide levels are unaltered. C16-ceramide synthesis in vitro is not increased. Levels of C22-, C24:0-, and C24:1-sphingolipids are reduced by 10-100fold in the CerS2 null mouse, but no significant reduction is seen in C20-sphingolipids. Levels of C26:1- and C26:0-sphingolipids are relatively low in the wild-type, and only a small reduction is observed in the CerS2 null mouse. Levels of sphinganine are significantly elevated by up to 50fold, reminiscent of the effect of the ceramide synthase inhibitor fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways are significantly changed. Total glycerophospholipid and cholesterol levels are unaltered, although there is a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids. Liver microsomal membranes from CerS2 null mice display higher membrane fluidity and show morphological changes. Expression of CerS5 is increased in the Cers2 mutants, and of CerS6 slightly. Mutant phenotype, overview Mus musculus
physiological function critical role for ceramide synthase 2 in liver homeostasis, molecular changes leading to hepatopathy, overview. Isozyme CerS2 can utilize a wider range of fatty acyl-CoAs but uses mainly C22 to C24. In addition, CerS2 displays complex modes of regulation and has genomic features characteristic of a housekeeping gene, no other CerS genes display these characteristics Mus musculus