PXD029496-1

PXD029496 is an original dataset announced via ProteomeXchange.

Title	A novel C-terminal DxRSDxE motif in ceramide synthases involved in dimer formation
Description	Ceramide 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.
HostingRepository	PRIDE
AnnounceDate	2022-02-18
AnnouncementXML	Submission_2022-02-18_09:11:04.519.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meital Kupervaser
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-02 03:54:49	ID requested
⏵ 1	2022-02-18 09:11:04	announced
2	2023-11-14 08:54:40	announced	2023-11-14: Updated project metadata.

10.1016/J.JBC.2021.101517;

submitter keyword: Ceramide, ceramide synthase, dimer, motif, sphingolipids

Anthony, H, Futerman
contact affiliation	Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
contact email	tony.futerman@weizmann.ac.il
lab head
Meital Kupervaser
contact affiliation	Weizmann Institute of Science
contact email	meital.kupervaser@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029496
     1. Label: PRIDE project
     2. Name: A novel C-terminal DxRSDxE motif in ceramide synthases involved in dimer formation