PXD040914

PXD040914 is an original dataset announced via ProteomeXchange.

Title	Polymorphic Histidine-rich Glycoprotein LC-MS/MS
Description	Histidine-rich glycoprotein (HRG) HRG is a liver-produced protein circulating in human plasma serum at high concentrations of around 125 ug/mL. HRG belongs to the family of type-3 cystatins and has been implicated in a plethora of biological processes, albeit its precise function is still not well understood. Human HRG is a highly polymorphic protein, with at least 5 variants with minor allele frequencies (MAF) of more than 10%, variable in populations from different parts of the world. Considering these 5 mutations we can expect already 35 = 243 possible possibly genetic HRG variants in the population. Here, we purified HRG from serum of 44 individual donors and investigated by proteomics the occurrence of different allotypes, each being either homozygote or heterozygote for each of the 5 mutation sites. We observed that some mutational combinations in HRG were highly favored, while others were apparently missing, although they ought to be present based on the stochastic independent assembly of these 5 mutation sites. To further explore this behavior, we extracted data from the 1000 genome project (n ~ 2500 genomes) and assessed the frequency of different HRG mutants in this larger dataset, observing a prevailing agreement with our proteomics data. From all the proteogenomic data we conclude that the 5 different (frequent) mutations sites in HRG are not occurring independently, but some mutational variants at different sites are fully mutually exclusive, whereas other are highly intwined. Specific mutations also affect HRG abundance and its glycosylation. As the levels of HRG have been suggested as a protein biomarker in a variety of biological processes (e.g., aging, COVID-19 severity, severity of bacterial infections), we here conclude that the highly polymorphic nature of the protein needs to be considered in such evaluations, as these mutations affect HRG’s abundance, structure, post-translational modifications, and function.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:09:39.328.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; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-16 07:10:12	ID requested
1	2023-10-24 12:16:30	announced
⏵ 2	2023-11-14 09:09:41	announced	2023-11-14: Updated project metadata.

Zou Y, van Breukelen B, Pronker M, Reiding K, Heck AJR, Proteogenomic Features of the Highly Polymorphic Histidine-rich Glycoprotein Arose Late in Evolution. Mol Cell Proteomics, 22(7):100585(2023) [pubmed]

submitter keyword: Serum proteomics

histidine-rich glycoprotein (HRG)

plasma proteomics

protein biomarker

proteogenomics

1000-genome

Albert J.R. Heck
contact affiliation	1 Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, the Netherlands 2 Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands
contact email	A.J.R.Heck@uu.nl
lab head
Yang Zou
contact affiliation	Utrecht University
contact email	y.zou2@uu.nl
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/2023/10/PXD040914

PRIDE project URI

• PRIDE
  1. PXD040914
     1. Label: PRIDE project
     2. Name: Polymorphic Histidine-rich Glycoprotein LC-MS/MS