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PXD053014

PXD053014 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIn vivo Mapping of the Mouse Galnt3-specific O-Glycoproteome
DescriptionThe UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The GALNT3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis (HFTC) due to impaired glycosylation of the phosphate-regulating hormone FGF23 within osteocytes of the bone. Patients with hyperphosphatemia present altered bone density, abnormal tooth structure and calcified masses throughout the body. It is therefore important to identify all potential substrates of GalNAc-T3 throughout the body to understand the complex disease phenotypes. Here, we compared the Galnt3-/- mouse model, which partially phenocopies GALNT3-CDG, with wild-type mice and employed a multi-component approach utilizing chemoenzymatic conditions, a product-dependent method constructed using EThcD triggered scans in a mass spectrometry workflow, quantitative O-glycoproteomics, and global proteomics to identify 663 Galnt3-specific O-glycosites from 269 glycoproteins across multiple tissues. Consistent with the mouse and human phenotypes, functional networks of glycoproteins that contain GalNAc-T3-specific O-glycosites involved in skeletal morphology, mineral level maintenance and hemostasis were identified. This library of in vivo GalNAc-T3-specific substrate proteins and O-glycosites will serve as a valuable resource to understand the functional implications of O-glycosylation and to unravel the underlying causes of complex human GALNT3-CDG phenotypes.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-06_19:04:24.021.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKruti Dalal
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListcomplex glycosylation
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-06-11 09:27:42ID requested
12025-05-06 19:04:26announced
Publication List
10.1016/j.jbc.2024.107628;
Dalal K, Yang W, Tian E, Chernish A, McCluggage P, Lara AJ, Ten Hagen KG, Tabak LA, vivo mapping of the mouse Galnt3-specific O-glycoproteome. J Biol Chem, 300(9):107628(2024) [pubmed]
Keyword List
submitter keyword: mass spectrometry,GalNAc-T
GALNT
Glycopeptides
Glycosyltransferase
Hyperphosphatemic Familial Tumoral Calcinosis (HFTC)
O-GalNAc
O-glycosylation
Contact List
Lawrence A. Tabak
contact affiliationBiological Chemistry Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States
contact emaillawrence.tabak@nih.gov
lab head
Kruti Dalal
contact affiliationNational Institute of Dental and Craniofacial Research, National Institutes of Health
contact emailkruti.dalal@nih.gov
dataset submitter
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Dataset FTP location
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