PXD023943-1

PXD023943 is an original dataset announced via ProteomeXchange.

Title	Glycoproteomic and phenotypic elucidation of B4GALNT2 expression variants in the SID histo-blood group system
Description	The Sda histo-blood group antigen [GalNAcβ1-4(NeuAcα2-3)Galβ-R] is present in colon, kidney and body fluids among 96-98% of Europeans whilst 90% have Sda-positive erythrocytes. Sda is implicated in various infections and constitutes a potential biomarker for colon cancer. The 2-4% truly Sd(a‒) individuals may produce anti-Sda, which can lead to incompatible blood transfusions, especially if donors with the high-expressing Sda phenotype, Sd(a++) or Cad, are involved. It was hypothesized that defects in the B4GALNT2-encoded β4GalNAc-T2 glycosyltransferase underlies the null phenotype. We recently reported the association of B4GALNT2 mutations with the Sd(a‒) phenotype, which formally established the SID blood-group system. In the present study, we provide causal proof and glycoprotein profiling underpinning this correlation. Phenotypically Sd(a‒) HEK293 cells were transfected with different B4GALNT2 constructs and evaluated by immunostaining and LC-MS/MS-based glycoproteomics. The pre¬dominant SIDnull allele with SNP rs7224888:T>C (p.Cys406Arg) abolished Sda synthesis, while this antigen was detectable as N- or O-glycans on multiple glycoproteins following transfection of wildtype B4GALNT2. Surprisingly, two rare missense SNPs, rs148441237:A>G and rs61743617:C>T, found in a Sd(a‒) compound heterozygote gave results similar to wildtype. To elucidate if Sd(a++)/Cad is also due to B4GALNT2 alterations, its coding region and 2 kbp upstream were sequenced in five Cad individuals. No genetic changes were associated with this phenotype but a detailed erythroid Cad glycoprotein profile was obtained, especially for GLPA (O-glycosylation) and, for the first time, B3AT (N-glycosylation). In conclusion, the p.Cys406Arg β4GalNAc-T2 variant causes Sda-deficiency in humans, while the enigmatic Cad phenotype remains unresolved, albeit further characterized.
HostingRepository	PRIDE
AnnounceDate	2022-04-07
AnnouncementXML	Submission_2022-04-07_03:44:55.645.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonas Nilsson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-02 06:41:26	ID requested
⏵ 1	2022-04-07 03:44:56	announced

Dataset with its publication pending

submitter keyword: SID blood group system, carbohydrate biosynthesis, erythrocyte, flow cytometry, gene expression, glycobiology, glycoprotein, glycopeptide, glycosylation, glycosyltransferase

Martin L Olsson
contact affiliation	Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
contact email	Martin_L.Olsson@med.lu.se
lab head
Jonas Nilsson
contact affiliation	University of Gothenburg
contact email	jonas.nilsson@clinchem.gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023943
     1. Label: PRIDE project
     2. Name: Glycoproteomic and phenotypic elucidation of B4GALNT2 expression variants in the SID histo-blood group system