PXD055397

PXD055397 is an original dataset announced via ProteomeXchange.

Title	Glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts
Description	SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3 and follows an autosomal recessive inheritance pattern. The enzyme encoded by SRD5A3, polyprenal reductase, plays a crucial role in synthesizing lipid precursors essential for N-linked glycosylation. Despite insights from functional studies into its enzymatic function, there remains a gap in understanding global changes in patient cells. We sought to identify glycoproteomic and proteomic signatures specific to SRD5A3-CDG, potentially aiding in biomarker discovery and advancing our understanding of disease mechanisms. Using tandem mass tag (TMT)-based relative quantitation, we analyzed fibroblasts derived from five patients along with control fibroblasts. Glycoproteomics analysis by liquid chromatography–tandem mass spectrometry (LC-MS/MS) identified 3,047 glycopeptides with 544 unique glycosylation sites from 276 glycoproteins. Of these, 418 glycopeptides showed statistically significant changes with 379 glycopeptides decreased (p<0.05) in SRD5A3-CDG patient-derived samples. These included high mannose, complex and hybrid glycan-bearing glycopeptides. High mannose glycopeptides from protocadherin Fat 4 and integrin alpha-11 and complex glycopeptides from CD55 were among the most significantly decreased glycopeptides. Proteomics analysis led to the identification of 5,933 proteins, of which 873 proteins showed statistically significant changes. Decreased proteins included cell surface glycoproteins, various mitochondrial protein populations and proteins involved in the N-glycosylation pathway. Lysosomal proteins such as N-acetylglucosamine-6-sulfatase and procathepsin-L also showed reduced levels of phosphorylated mannose-containing glycopeptides. Our findings point to disruptions in glycosylation pathways as well as energy metabolism and lysosomal functions in SRD5A3-CDG, providing clues to improved understanding and management of patients with this disorder.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_02:41:44.020.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; complex glycosylation; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-30 10:56:33	ID requested
⏵ 1	2025-05-07 02:41:44	announced

Garapati K, Ranatunga W, Joshi N, Budhraja R, Sabu S, Kantautas KA, Preston G, Perlstein EO, Kozicz T, Morava E, Pandey A, N-glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts. Glycobiology, 34(11):(2024) [pubmed]

10.1093/glycob/cwae076;

submitter keyword: dolichol, lipid-linked oligosaccharide, CDG type I,N-glycosylation, polyprenol

Akhilesh Pandey, M.D., Ph.D.
contact affiliation	Akhilesh Pandey, M.D., Ph.D. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, United States
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.edu
dataset submitter

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/2025/05/PXD055397

PRIDE project URI

• PRIDE
  1. PXD055397
     1. Label: PRIDE project
     2. Name: Glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts