» Articles » PMID: 31273262

ABO Blood Group A Transferase and Its Codon 69 Substitution Enzymes Synthesize FORS1 Antigen of FORS Blood Group System

Overview
Journal Sci Rep
Specialty Science
Date 2019 Jul 6
PMID 31273262
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

Human histo-blood group A transferase (AT) catalyzes the biosynthesis of oligosaccharide A antigen important in blood transfusion and cell/tissue/organ transplantation. This enzyme may synthesize Forssman antigen (FORS1) of the FORS blood group system when exon 3 or 4 of the AT mRNA is deleted and/or the LeuGlyGly tripeptide at codons 266-268 of AT is replaced by GlyGlyAla. The Met69Ser/Thr substitutions also confer weak Forssman glycolipid synthase (FS) activity. In this study, we prepared the human AT derivative constructs containing any of the 20 amino acids at codon 69 with and without the GlyGlyAla substitution, transfected DNA to newly generated COS1(B3GALNT1 + A4GALT) cells expressing an enhanced level of globoside (Gb4), the FS acceptor substrate, and immunologically examined the FORS1 expression. Our results showed that all those substitution constructs at codon 69 exhibited FS activity. The combination with GlyGlyAla significantly increased the activity. The conserved methionine residue in the ABO, but not GBGT1, gene-encoded proteins may implicate its contribution to the separation of these genes in genetic evolution. Surprisingly, with increased Gb4 availability, the original human AT with the methionine residue at codon 69 was also demonstrated to synthesize FORS1, providing another molecular mechanism of FORS1 appearance in cancer of ordinary FORS1-negative individuals.

Citing Articles

Genetic and Epigenetic Intersections in COVID-19-Associated Cardiovascular Disease: Emerging Insights and Future Directions.

Sabit H, Arneth B, Altrawy A, Ghazy A, Abdelazeem R, Adel A Biomedicines. 2025; 13(2).

PMID: 40002898 PMC: 11852909. DOI: 10.3390/biomedicines13020485.


Carbohydrate-active enzymes from Akkermansia muciniphila break down mucin O-glycans to completion.

Bakshani C, Ojuri T, Pilgaard B, Holck J, McInnes R, Kozak R Nat Microbiol. 2025; 10(2):585-598.

PMID: 39891011 PMC: 11790493. DOI: 10.1038/s41564-024-01911-7.


ABO Blood System: Biosynthesis of Agglutinogenic Alkaline and Non-Agglutinogenic Acid Glycotopes of A and B Antigens at Different pHs of the Culture Medium.

Delevsky Y, Zinchenko O Arch Razi Inst. 2024; 79(1):55-67.

PMID: 39192948 PMC: 11345478. DOI: 10.32592/ARI.2024.79.1.55.


Are tumor-associated carbohydrates the missing link between the gut microbiome and response to immune checkpoint inhibitor treatment in cancer?.

Szallasi Z, Prosz A, Sztupinszki Z, Moldvay J Oncoimmunology. 2024; 13(1):2324493.

PMID: 38445083 PMC: 10913702. DOI: 10.1080/2162402X.2024.2324493.


The stem region of group A transferase is crucial for its specificity, and its alteration promotes heterologous Forssman synthase activity.

Cid E, Yamamoto M, Barrero L, Yamamoto F Sci Rep. 2023; 13(1):13996.

PMID: 37634031 PMC: 10460411. DOI: 10.1038/s41598-023-40900-4.


References
1.
WATKINS W . The ABO blood group system: historical background. Transfus Med. 2001; 11(4):243-65. DOI: 10.1046/j.1365-3148.2001.00321.x. View

2.
LEDUC E, Tanaka N . A study of the cellular distribution of Forssman antigen in various species. J Immunol. 1956; 77(3):198-212. View

3.
Harris P, Roman G, Moulds J, Bird G, Shah N . An inherited RBC characteristic, NOR, resulting in erythrocyte polyagglutination. Vox Sang. 1982; 42(3):134-40. DOI: 10.1111/j.1423-0410.1982.tb01083.x. View

4.
Yamamoto F, McNEILL P, Yamamoto M, Hakomori S, Bromilow I, Duguid J . Molecular genetic analysis of the ABO blood group system: 4. Another type of O allele. Vox Sang. 1993; 64(3):175-8. DOI: 10.1111/j.1423-0410.1993.tb05158.x. View

5.
Suchanowska A, Kaczmarek R, Duk M, Lukasiewicz J, Smolarek D, Majorczyk E . A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome. J Biol Chem. 2012; 287(45):38220-30. PMC: 3488091. DOI: 10.1074/jbc.M112.408286. View