A4GALT
- Known as:
- A4GALT
- Catalog number:
- 000858A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- A4GALT
Related genes to: A4GALT
- Gene:
- A4GALT NIH gene
- Name:
- alpha 1,4-galactosyltransferase (P blood group)
- Previous symbol:
- P1
- Synonyms:
- A14GALT, Gb3S, P(k)
- Chromosome:
- 22q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-06
- Date modifiied:
- 2019-04-23
Related products to: A4GALT
Related articles to: A4GALT
- Fabry disease (FD), one of the most prevalent lysosomal storage disorders in Europe, is caused by mutations in the GLA gene leading to deficient α-galactosidase A activity with lysosomal accumulation of globotriaosylceramide (Gb3). Enzyme replacement therapy (ERT) and pharmacological chaperone therapy (PCT) are used in the clinic to treat FD but are limited in efficacy, underscoring the need for alternative therapeutic strategies. Inhibiting α-1,4-galactosyltransferase (A4GALT), the glycosyltransferase responsible for Gb3 biosynthesis, represents an attractive strategy. Here, we reveal the molecular mechanism of human A4GALT at atomic detail using QM/MM simulations. We reveal a conformational rearrangement involving a 3-helix that stabilizes the donor substrate and promotes a front-face Si-like catalytic mechanism, in which a short-lived oxocarbenium-ion intermediate forms. The simulations informed the synthesis of a panel of glycosylceramide substrate analogues. Among these, AdaGalCer (Ada = adamantyl) proved able to reduce Gb3 production in fibroblasts while simultaneously being converted by A4GALT into the galactosylated product AdaGb2. These results provide a clear path towards inhibiting A4GALT, paving the way for potential new and effective FD therapeutics. - Source: PubMed
Publication date: 2026/08/06
de Koster NickyVidal-Gironès Òscarde Graaf RowanKok KenLelieveld Lindsey THoogervorst JackelienFerraz Maria JRivas-Fernández José PabloLammers Rob FOverkleeft Herman SAerts Johannes M F GBoot Rolf GRovira CarmeArtola Marta - - Source: PubMed
Publication date: 2026/07/15
Tian XueChu XiaoyueXiang DongZhang LiangziXu Hua - - Source: PubMed
Publication date: 2026/07/15
Zhang JingZhang YingWang YingjianSong TiejunDai FengXu ShoufangZhang YingyingJiang FeiyuLiu Zhiwei - BACKGROUND: Tumor lipid metabolism has emerged as a critical, yet underexplored, determinant of cancer progression with clinical and prognostic importance. A membrane lipid species of particular interest is globotriaosylceramide (Gb3/CD77), a glycosphingolipid that serves as cellular receptor for the bacterial Shiga toxins, and is upregulated in various malignancies. While preclinical studies have suggested a pro-tumorigenic role for Gb3, the regulatory drivers of its biosynthesis in human tumors have remained elusive. METHODS: The glycosyltransferase A4GALT, responsible for Gb3 biosynthesis, and the degrading enzyme α-galactosidase A (α-GLA) are two essential molecular determinants of Gb3 cell surface expression. Expression of these enzymes was analyzed on mRNA level in tissues from colorectal cancer, published datasets from gastric, pancreatic, esophageal and colorectal cancer (1213 patients) and in human cell lines. Pharmacological manipulation in vitro using the hypomethylating agent 5-Aza-2-deoxycytidine and histone deacetylase (HDAC) inhibitors induced A4GALT expression in DLD1 colon cancer cells and Gb3 biosynthesis. A4GALT deficiency was induced by CRISPR-Cas9 mutagenesis in human HCT116 colon cancer cells, and its putative effects tested for proliferation, cell migration and invasion. RESULTS: A4GALT deficiency in HCT116 cells confirmed its essential role for Gb3 biosynthesis, leading to resistance against Shiga toxin 1a, and to reduced cancer cell migration and invasion. Gene enrichment analyses revealed that high A4GALT and low α-GLA expression is associated with a distinct gene expression program in gastric, pancreatic and colorectal cancer, including increased signatures of epithelial–mesenchymal transition. A4GALT expression is regulated by chromatin accessibility and DNA methylation at a defined intronic enhancer. In accordance, pan‑cancer analysis of TCGA datasets validated the A4GALT‑high/α‑GLA‑low signature as a negative prognostic indicator across gastrointestinal tumor entities. CONCLUSIONS: Our study uncovers an epigenetically regulated lipid metabolic axis involving A4GALT and Gb3 that contributes to aggressive tumor behavior. Of note, this pathway may be therapeutically targetable using natural or synthetic Shiga toxin B-subunit derivatives. - Source: PubMed
Publication date: 2026/01/27
Hirsch Noah-DavidPerl MarkusHolzinger SimonBarz ChristophEnßle StefanJohannes WidyaConrad AnjaUnterholzner Jonas JObermeier ViktoriaTschurtschenthaler MarkusJohannes LudgerJanssen Klaus-Peter - The P1PK blood group system in humans, composed of three glycosphingolipid antigens, plays a significant role in transfusion medicine. These antigens are synthesized by the enzyme α1,4-galactosyltransferase, encoded by the A4GALT gene, and also act as receptors for Shiga toxins, which are key virulence factors produced by pathogenic strains of Escherichia coli. Birds are known to be resistant to the effects of Shiga toxins, yet the molecular basis of this resistance has remained unclear. This study aimed to investigate the presence, expression, and functional role of P1PK antigens in birds, particularly in relation to their exposure to human-associated bacteria. - Source: PubMed
Publication date: 2025/12/17
Bereznicka AnnaDuk MariaKapczynska KatarzynaModlinska AnnaPiasecki TomaszLink-Lenczowski PawełHeidorn-Czarna MałgorzataPasikowski PawelCzerwinski MarcinKaczmarek Radoslaw