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Molecular genetic basis of the human Forssman glycolipid antigen negativity
Forssman heterophilic glycolipid antigen has structural similarity to the histo-blood group A antigen, and the GBGT1 gene encoding the Forssman glycolipid synthetase (FS) is evolutionarily related to the ABO gene. The antigen is present in various species, but not in others including humans. We have...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521167/ https://www.ncbi.nlm.nih.gov/pubmed/23240079 http://dx.doi.org/10.1038/srep00975 |
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author | Yamamoto, Miyako Cid, Emili Yamamoto, Fumiichiro |
author_facet | Yamamoto, Miyako Cid, Emili Yamamoto, Fumiichiro |
author_sort | Yamamoto, Miyako |
collection | PubMed |
description | Forssman heterophilic glycolipid antigen has structural similarity to the histo-blood group A antigen, and the GBGT1 gene encoding the Forssman glycolipid synthetase (FS) is evolutionarily related to the ABO gene. The antigen is present in various species, but not in others including humans. We have elucidated the molecular genetic basis of the Forssman antigen negativity in humans. In the human GBGT1 gene, we identified two common inactivating missense mutations (c.688G>A [p.Gly230Ser] and c.887A>G [p.Gln296Arg]). The reversion of the two mutations fully restored the glycosyltransferase activity to synthesize the Forssman antigen in vitro. These glycine and glutamine residues are conserved among functional GBGT1 genes in Forssman-positive species. Furthermore, the glycine and serine residues represent those at the corresponding position of the human blood group A and B transferases with GalNAc and galactose specificity, respectively, implicating the crucial role the glycine residue may play in the FS α1,3-GalNAc transferase activity. |
format | Online Article Text |
id | pubmed-3521167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-35211672012-12-13 Molecular genetic basis of the human Forssman glycolipid antigen negativity Yamamoto, Miyako Cid, Emili Yamamoto, Fumiichiro Sci Rep Article Forssman heterophilic glycolipid antigen has structural similarity to the histo-blood group A antigen, and the GBGT1 gene encoding the Forssman glycolipid synthetase (FS) is evolutionarily related to the ABO gene. The antigen is present in various species, but not in others including humans. We have elucidated the molecular genetic basis of the Forssman antigen negativity in humans. In the human GBGT1 gene, we identified two common inactivating missense mutations (c.688G>A [p.Gly230Ser] and c.887A>G [p.Gln296Arg]). The reversion of the two mutations fully restored the glycosyltransferase activity to synthesize the Forssman antigen in vitro. These glycine and glutamine residues are conserved among functional GBGT1 genes in Forssman-positive species. Furthermore, the glycine and serine residues represent those at the corresponding position of the human blood group A and B transferases with GalNAc and galactose specificity, respectively, implicating the crucial role the glycine residue may play in the FS α1,3-GalNAc transferase activity. Nature Publishing Group 2012-12-13 /pmc/articles/PMC3521167/ /pubmed/23240079 http://dx.doi.org/10.1038/srep00975 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Yamamoto, Miyako Cid, Emili Yamamoto, Fumiichiro Molecular genetic basis of the human Forssman glycolipid antigen negativity |
title | Molecular genetic basis of the human Forssman glycolipid antigen negativity |
title_full | Molecular genetic basis of the human Forssman glycolipid antigen negativity |
title_fullStr | Molecular genetic basis of the human Forssman glycolipid antigen negativity |
title_full_unstemmed | Molecular genetic basis of the human Forssman glycolipid antigen negativity |
title_short | Molecular genetic basis of the human Forssman glycolipid antigen negativity |
title_sort | molecular genetic basis of the human forssman glycolipid antigen negativity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521167/ https://www.ncbi.nlm.nih.gov/pubmed/23240079 http://dx.doi.org/10.1038/srep00975 |
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