PXD044353 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Genotype-dependent N-glycosylation and newly discovered O-glycosylation affecting HRG plasmin cleavage |
Description | Histidine-rich glycoprotein (HRG) is an abundant plasma glycoprotein with three reported N-glycosylation sites, which integrates many biological processes such as antiangiogenic activity, immune complex clearance and pathogen clearance. Importantly, the protein is known to have five genetic variants with minor allele frequencies of more than 10%, meaning these exist with substantial frequency in the human population. Among them, Pro204Ser can induce a new N-glycosylation site at Asn202. Considerable research has been performed into the biological activity of HRG, while research on its glycosylation is rare. To close this knowledge gap, we used C18-based LC-MS/MS to investigate the glycosylation characteristics of HRG from human plasma, recombinant Chinese hamster ovary (CHO) cell lines and recombinant human embryonic kidney (HEK293) cell lines with targeted mutations. Within human plasma endogenous HRG, every N-glycosylation site proved dominant with a sialylated diantennary complex-type glycan. For the recombinant HRGs, on the other hand, glycans showed different antennarities, sialylation and core-fucosylation, as well as the appearance of oligomannose glycans, LacdiNAc and antennary fucosylation. Furthermore, we discovered a previously unreported O-glycosylation site on residues Thr273/Thr274, which showed an approximate 90% glycan occupancy in all HRG types. To investigate the relevance of HRG glycosylation characteristics and its biological function, we set up an assay to study the plasmin cleavage of HRG under various conditions. In doing so, we showed that the sialylation of the new O-glycan, as well as the genotype-dependent N-glycosylation, significantly influenced the plasmin cleavage of HRG. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-21 |
AnnouncementXML | Submission_2024-05-21_12:07:20.282.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Yang Zou |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | carboxylated residue; phosphorylated residue; monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos; Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-08-04 05:20:05 | ID requested | |
⏵ 1 | 2024-05-21 12:07:21 | announced | |
Publication List
10.1016/j.jbc.2024.105683; |
Zou Y, Pronker MF, Damen JMA, Heck AJR, Reiding KR, Genotype-dependent N-glycosylation and newly exposed O-glycosylation affect plasmin-induced cleavage of histidine-rich glycoprotein (HRG). J Biol Chem, 300(3):105683(2024) [pubmed] |
Keyword List
submitter keyword: histidine-rich glycoprotein (HRG), O-glycosylation, glycoproteomics, plasmin cleavage,N-glycosylation |
Contact List
Karli Reiding |
contact affiliation | 1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands 2Netherlands Proteomics Center, Padualaan 8, 3584 CH, Utrecht, The Netherlands |
contact email | k.r.reiding@uu.nl |
lab head | |
Yang Zou |
contact affiliation | Utrecht University |
contact email | y.zou2@uu.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044353
- Label: PRIDE project
- Name: Genotype-dependent N-glycosylation and newly discovered O-glycosylation affecting HRG plasmin cleavage