Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype.
-
A4GALT expression restores P(k) antigen in P(k)-negative Namalwa cells.
"Transfection of P(k)-negative Namalwa cells with alpha4Gal-T1 resulted in strong P(k) expression."
-
Homozygous M183K was identified in six Swedish individuals with the p phenotype.
"A single homozygous missense mutation, M183K, was found in six Swedish individuals of the rare p phenotype"
-
The original study concluded that A4GALT did not encode P1 synthase activity.
"but not P(1) synthase activity"
Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids.
-
Expression cloning of the A4GALT cDNA (Gb3/CD77 synthase) produced alpha-1,4-galactosyltransferase activity on lactosylceramide (and galactosylceramide), yielding Gb3/CD77 and initiating globo-series glycosphingolipid synthesis; the protein is a type II membrane protein.
"the extracts of the transfectant cells showed alpha1, 4-galactosyltransferase activity only on lactosylceramide and galactosylceramide"
Glycosphingolipid biosynthesis
A4GALT transfers galactose to LacCer
UniProt entry Q9NPC4 (A4GAT_HUMAN), Lactosylceramide 4-alpha-galactosyltransferase
-
A4GALT is a Golgi apparatus membrane, single-pass type II membrane glycosyltransferase (EC 2.4.1.228) that transfers galactose from UDP-alpha-D-galactose in an alpha-1,4 linkage to lactosylceramide to produce globotriaosylceramide/Gb3Cer (P(k)/CD77 antigen), the root structure of the globo-series neutral glycosphingolipids.
"SUBCELLULAR LOCATION: Golgi apparatus membrane"
Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating P(k), P1 and NOR blood group antigens.
-
Direct biochemical assays show that wild-type A4GALT synthesizes both P(k) and P1; Q211E adds NOR acceptor specificity.
"the consensus enzyme synthesizes both the P(k) and P1 antigens, while its p.Q211E variant additionally synthesizes the NOR antigen"
Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry.
-
Recombinant and transfected-cell assays demonstrate P1 glycotope synthesis on complex N-glycans. The glycoprotein products, rather than the A4GALT enzyme, can act as Stx1 receptors.
"both enzymes produce P1 glycotopes on N-glycoproteins, with the mutein exhibiting elevated activity."
A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome.
-
Q211E broadens A4GALT acceptor specificity to produce NOR antigens, a mechanism distinct from p-null loss of function.
"Cells transfected with the vector encoding the Gb3/CD77 synthase with Glu at position 211 expressed both P1 and NOR antigens."
Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals.