PXD049174 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis |
Description | Dolichol is a lipid critical for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. It is commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires a three-step detour involving additional metabolites, where SRD5A3 catalyzes only the second reaction. The first and third steps are performed by DHRSX, whose gene resides on the pseudoautosomal regions of the X and Y chromosomes. Accordingly, we report a pseudoautosomal-recessive disease presenting as a congenital disorder of glycosylation in patients with missense variants in DHRSX (DHRSX-CDG). Of note, DHRSX has a unique dual substrate and cofactor specificity, allowing it to act as a NAD+-dependent dehydrogenase and as a NADPH-dependent reductase in two non-consecutive steps. Thus, our work reveals unexpected complexity in the terminal steps of dolichol biosynthesis. Furthermore, we provide insights into the mechanism by which dolichol metabolism defects contribute to disease. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:44:33.455.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD049174 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Francesco Caligiore |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Hex1HexNAc2 N4-glycosylated asparagine; Hex7HexNAc2 N4-glycosylated asparagine; Hex3HexNAc2 N4-glycosylated asparagine; Hex2HexNAc2 N4-glycosylated asparagine; Hex9HexNAc2 N4-glycosylated asparagine; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-02-05 03:44:37 | ID requested | |
1 | 2024-06-12 00:28:59 | announced | |
⏵ 2 | 2024-10-22 06:44:34 | announced | 2024-10-22: Updated project metadata. |
Publication List
Wilson MP, Kentache T, Althoff CR, Schulz C, de Bettignies G, Mateu Cabrera G, Cimbalistiene L, Burnyte B, Yoon G, Costain G, Vuillaumier-Barrot S, Cheillan D, Rymen D, Rychtarova L, Hansikova H, Bury M, Dewulf JP, Caligiore F, Jaeken J, Cantagrel V, Van Schaftingen E, Matthijs G, Foulquier F, Bommer GT, A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. Cell, 187(14):3585-3601.e22(2024) [pubmed] |
10.6019/PXD049174; |
10.1016/j.cell.2024.04.041; |
Keyword List
submitter keyword: Lipid droplets, Congenital Disorders of Glycosylation, Polyprenal, N-glycosylation, Dolichal, Pseudoautosomal Region,Dolichol, Polyprenol |
Contact List
Guido T. |
contact affiliation | de Duve Institute UCLouvain and WELBIO |
contact email | guido.bommer@uclouvain.be |
lab head | |
Francesco Caligiore |
contact affiliation | UCLouvain |
contact email | francesco.caligiore@uclouvain.be |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD049174 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD049174
- Label: PRIDE project
- Name: A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis