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PXD029496-1

PXD029496 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA novel C-terminal DxRSDxE motif in ceramide synthases involved in dimer formation
DescriptionCeramide is synthesized via the ceramide synthases (CerSs), six of which have been identified in mammalian cells, with each using a unique subset of acyl-CoAs for ceramide synthesis. The CerSs are part of a larger gene family, the Tram-Lag-CLN8 (TLC) domain family. We now identify a unique, C-terminal motif, the DxRSDxE motif, which is only found in CerS and not in other TLC family members. Deletion of this motif in either CerS2-HA or in CerS6-Flag did not affect the ability of either to generate ceramide using both an in vitro assay and upon metabolic labeling, but deletion of this motif did affect the activity of CerS2-HA when co-expressed with CerS6-Flag. Surprisingly, transfection of cells with either CerS2-HA or CerS6-Flag lacking the motif did not result in changes in cellular ceramide levels. CerS2-HA and CerS6-Flag interact with each other, as shown by immunoprecipitation, but deletion of the DxRSDxE motif impedes this interaction. Moreover, proteomics analysis of cells transfected with CerS6Δ338-344-Flag indicated that deletion of the C-terminal motif impacted cellular protein expression, and in particular, levels of ORMDL1, a negative regulator of sphingolipid synthesis. We suggest that this novel C-terminus motif regulates CerS dimer formation and thereby impacts ceramide synthesis.
HostingRepositoryPRIDE
AnnounceDate2022-02-18
AnnouncementXMLSubmission_2022-02-18_09:11:04.519.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMeital Kupervaser
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-02 03:54:49ID requested
12022-02-18 09:11:04announced
22023-11-14 08:54:40announced2023-11-14: Updated project metadata.
Publication List
10.1016/J.JBC.2021.101517;
Keyword List
submitter keyword: Ceramide, ceramide synthase, dimer, motif, sphingolipids
Contact List
Anthony, H, Futerman
contact affiliationDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
contact emailtony.futerman@weizmann.ac.il
lab head
Meital Kupervaser
contact affiliationWeizmann Institute of Science
contact emailmeital.kupervaser@weizmann.ac.il
dataset submitter
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Dataset FTP location
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