PXD073937

PXD073937 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	PRIDE
AnnounceDate	2026-08-02
AnnouncementXML	Submission_2026-08-01_23:46:20.658.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adnan Halim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	mannosylated residue; N-acetylaminogalactosylated
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-02 12:05:37	ID requested
⏵ 1	2026-08-01 23:46:21	announced

10.1016/j.ymgme.2026.110115;

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: ALG3

POMT1

POMT2

KIAA1549

N-glycosylation

O-mannosylation

Adnan Halim
contact affiliation	Copenhagen Center for Glycocalyx Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark
contact email	halim@sund.kud.k
lab head
Adnan Halim
contact affiliation	University of Copenhagen
contact email	halim@sund.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073937
     1. Label: PRIDE project
     2. Name: Truncated N-glycans destabilize POMT1 and POMT2 but do not limit cellular O-mannosylation in HEK293 cells