The successive addition of three glucose residues by EC 2.4.1.267, EC 2.4.1.265 (Dol-P-Glc:Glc1Man9GlcNAc2-PP-Dol alpha-1,3-glucosyltransferase) and EC 2.4.1.256 (Dol-P-Glc:Glc2Man9GlcNAc2-PP-Dol alpha-1,2-glucosyltransferase) represents the final stage of the lipid-linked oligosaccharide assembly.
The successive addition of three glucose residues by EC 2.4.1.267, EC 2.4.1.265 (Dol-P-Glc:Glc1Man9GlcNAc2-PP-Dol alpha-1,3-glucosyltransferase) and EC 2.4.1.256 (Dol-P-Glc:Glc2Man9GlcNAc2-PP-Dol alpha-1,2-glucosyltransferase) represents the final stage of the lipid-linked oligosaccharide assembly.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Frequency Determination of ?-1,3 Glucosyltransferase p.Y131H and p.F304S Polymorphisms in the Croatian Population Revealed Five Novel Single Nucleotide Polymorphisms in the hALG6 Gene.
alg6-1 mutants accumulate Man9GlcNAc2-P-P-dolichol as their largest lipid-linked oligosaccharide in vivo and in vitro. alg6-1 cells are unable to transfer glucose from dolichol phosphoglucose to the unglucosylated lipid-linked oligosaccharide
ALG6 deficient MI8-5 cells express 2fold lower levels of oligosaccharyltransferase STT3B than the parental Chinese hamster ovary cells. The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc2Man9Glc3 donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells
fibroblasts from an ALG6-congenital disorders of glycosylation patient that carries the A333V mutation on the maternal ALG6 allele and the S308R and Y131H mutations on the paternal ALG6 allele assemble Dol-PP-GlcNAc2Man9 as the largest oligosaccharide donor. 30–40% of oligosaccharyltransferase STT3A-dependent glycosylation sites and 20% of oligosaccharyltransferase STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts
analysis of lipid-linked oligosaccharides in cultured fibroblasts indicates accumulation of Man9GlcNAc2-PP-Dol. Sequence analysis of ALG6 reveals a deletion of exon 3 (c.257 + 5G > A) in combination with a missense mutation (c.998C > T, p.Ala333Val). The patient shows skeletal dysplasia with brachytelephalangy
patient with three mutations in the hALG6 gene. The maternal allele has an intronic G -> A mutation resulting in skipping of exon3 (IVS3 + 5G > A). This produces a nonfunctional enzyme as shown by its inability to restore normal glycosylation in a Saccharomyces cerevisiae strain lacking a functional ALG6. The paternal allele has two mutations. One is a deletion of three bases (895–897delATA) leading to an in-frame deletion of isoleucine 299 (delI299) located in a transmembrane domain. The second mutation on the same allele 911T > C causes a F304S change. When expressed in the ALG6 deficient yeast strain, this allele restores glycosylation but the mRNA is unstable or inefficiently transcribed, contributing to the impaired glycosylation in the patient
natural variant, common polymorphism reduces the ability to rescue defective glycosylation of an alg6-deficient strain of S. cerevisiae during rapid growth, may exacerbate the clinical severity of patients with CDG1A
frequent natural variant, the cause of congenital disorder of glycosylation-Ic (CDG-Ic). One patient with typical CDG-Ic symptoms and a homozygous p.Tyr131His alteration in ALG6. In contrast to most CDG patients, her LLO and plasma transferrin glycosylation appeared normal. Thus, it is unclear whether Y131H causes CDG-Ic or contributes to the symptoms
genetic engineering of N-glycan biosynthesis in Yarrowia lipolytica so that it produces Man(3)GlcNAc(2) structures on its glycoproteins. Disruption of the ALG3 gene, EC 2.4.1.258, results in modification of proteins mainly with Man(5)GlcNAc(2) and GlcMan(5)GlcNAc(2) glycans, and to a lesser extent with Glc(2)Man(5)GlcNAc(2) glycans. To avoid underoccupancy of glycosylation sites, Alg6, EC 2.4.1.267, is concomitantly overexpressed. Overexpression of the heterodimeric Aspergillus niger glucosidase II results in removal the terminal glucose residues. Overexpression of an alpha-1,2-mannosidase leads to Man(3)GlcNAc(2) structures, which are substrates for the synthesis of complex-type glycans. The final Yarrowia lipolytica strain produces proteins glycosylated with the trimannosyl core N-glycan (Man(3)GlcNAc(2)), which is the common core of all complex-type N-glycans
A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency
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Enzyme Nomenclature
2.4.1.267 dolichyl-P-Glc:Man9GlcNAc2-PP-dolichol alpha-1,3-glucosyltransferase
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