Summary

This gene catalyzes on of the addiction reactions in the early steps of N-linked glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. (from  )

Disease relevance of ALG8

• Alg8 shares 28.20% identity and 38.09% similarity to Azorhizobium caulinodans NodC, a glycosyl transferase catalyzing the formation of beta-1,4 linkages [1].
• A structural model of Alg8 based on the structure of SpsA from Bacillus subtilis was developed [2].

High impact information on ALG8

• Both mutations give rise to premature stop codons predicted to generate severely truncated proteins, but because the translation inhibitor emetine was shown to stabilize the hALG8 mRNA from the patient to normal levels, it is likely that both transcripts undergo nonsense-mediated mRNA decay [3].
• Fusion protein analysis provided evidence that Alg8 is located in the cytoplasmic membrane with a periplasmic C terminus [2].
• To determine the requirement of Alg8, which has been proposed as catalytic subunit of alginate polymerase, nonpolar isogenic alg8 knockout mutants of alginate-overproducing P. aeruginosa FRD1 and P. aeruginosa PDO300 were constructed, respectively [2].
• Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency) [4].

Analytical, diagnostic and therapeutic context of ALG8

• Northern blot analysis revealed the cells from the patient to possess only 10-20% normal amounts of mRNA encoding the enzyme, dolichyl-P-glucose:Glc(1)Man(9)GlcNAc(2)-PP-dolichyl alpha3-glucosyltransferase (hALG8p), which catalyzes this reaction [3].

References