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http://purl.uniprot.org/citations/35849604 | http://www.w3.org/2000/01/rdf-schema#comment | "The important membrane lipid, ceramide, is generated by a family of homologous enzymes, the ceramide synthases (CerSs), multi-spanning membrane proteins located in the endoplasmic reticulum. Six CerS isoforms exist in mammals with each using a subset of acyl-CoAs for (dihydro)ceramide synthesis. A number of mice have been generated in which one or other CerS has been genetically manipulated, including complete knock-outs, with each displaying phenotypes concomitant with the expression levels of the CerS in question and the presumed biological function of the ceramide species that it generates. We recently described a short C-terminal motif in the CerS which is involved in CerS dimer formation; deleting this motif had no effect on the ability of the CerS to synthesize ceramide in vitro. In the current study, we generated a CerS6 mouse using CRISPR-Cas9, in which the DDRSDIE motif was replaced by ADAAAIA. While levels of CerS6ADAAAIA expression were unaffected in the CerS6ADAAAIA mouse, and CerS6ADAAAIA was able to generate C16-ceramide in vitro, ceramide levels were significantly reduced in the CerS6ADAAAIA mouse, suggesting that replacing this motif affects an as-yet unknown mechanism of regulation of ceramide synthesis via the DDRSDIE motif in vivo. Crossing CerS6ADAAAIA mice with CerS5 null mice led to generation of viable mice in which C16-ceramide levels were reduced by up to 90%, suggesting that depletion of C16-ceramide levels is compensated for by other ceramide species with different acyl chain lengths."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0271675"xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/author | "Kim J."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/author | "Ben-Dor S."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/author | "Futerman A.H."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/author | "Pewzner-Jung Y."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/author | "Joseph T."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/pages | "e0271675"xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/title | "Generation of a ceramide synthase 6 mouse lacking the DDRSDIE C-terminal motif."xsd:string |
http://purl.uniprot.org/citations/35849604 | http://purl.uniprot.org/core/volume | "17"xsd:string |
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