PXD073179-1

PXD073179 is an original dataset announced via ProteomeXchange.

Title	Truncated N-glycans destabilize POMT1 and POMT2 but do not limit cellular O-mannosylation in HEK293 cells
Description	Protein O-mannosylation is initiated by the ER-resident enzymes POMT1 and POMT2, both of which carry multiple N-glycans essential for proper folding and activity. Although congenital disorders of glycosylation type I (CDG-I) disrupt the early N-glycosylation process, their impact on POMT biogenesis and O-mannosylation has remained unclear. Here, we show that ALG3-dependent N-glycan elongation is required to maintain normal abundance of POMT1 and POMT2. In ALG3-deficient HEK293 cells, POMTs carry truncated Man5-type N-glycans and their steady-state protein levels are reduced by more than half, despite unchanged transcript levels. In vitro, reduced POMT abundance resulted in a proportional decrease in mannosyltransferase activity. However, O-mannosylation in cells remained unaffected: α-dystroglycan displayed normal matriglycan extension and a highly O-mannosylated KIAA1549 reporter showed unaltered site occupancy and core structures. These data indicate that POMT activity operates with substantial catalytic reserve under basal conditions, sufficient to tolerate significant reduction in enzyme levels without impairing substrate modification. Our work identifies ALG3-mediated N-glycan maturation as a determinant of POMT stability, highlights buffering capacity within the O-mannosylation pathway, and provides a mechanistic framework for understanding how N-glycosylation defects could modulate POMT-dependent glycosylation in disease.
HostingRepository	PanoramaPublic
AnnounceDate	2026-04-13
AnnouncementXML	Submission_2026-04-13_14:01:49.914.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Daniel Sturm
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Phospho; Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	QTRAP 5500; nanoACQUITY UPLC

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-16 14:34:41	ID requested
⏵ 1	2026-04-13 14:01:50	announced

Sturm D, H, ö, lscher C, Mart, í, nez IA, Harst A, Konstantinidi A, Alam S, Burock R, Vakhrushev SY, Hoffmann M, Ruppert T, Rapp E, Halim A, Thiel C, Strahl S, Truncated N-glycans destabilize POMT1 and POMT2 but do not limit cellular O-mannosylation in HEK293 cells. Mol Genet Metab, 148(2):110115(2026) [pubmed]

submitter keyword: N-glycosylation, O-mannosylation, POMT1, ALG3, endoplasmic reticulum, glycosylation, glycosyltransferase

Sabine Strahl
contact affiliation	Heidelberg University, COS
contact email	sabine.strahl@cos.uni-heidelberg.de
lab head
Daniel Sturm
contact affiliation	Heidelberg University, COS
contact email	daniel.sturm@cos.uni-heidelberg.de
dataset submitter

Panorama Public dataset URI