Neutral alpha-glucosidase AB (GANAB) (GANAB)

Neutral alpha-glucosidase AB (GANAB) is a critical enzyme located in the lumen of the endoplasmic reticulum (ER) that serves as the catalytic alpha subunit of glucosidase II (UniProt P14314). It plays a pivotal role in the N-linked glycosylation pathway by sequentially removing the two innermost glucose residues from the Glc2Man9GlcNAc2 oligosaccharide precursor on newly synthesized glycoproteins (PubMed: 28373485). This process is essential for the glycoprotein's entry into the calnexin/calreticulin cycle, a quality control mechanism that ensures proper protein folding before trafficking to the Golgi apparatus (PubMed: 27230638). Mutations in the GANAB gene have been identified as a cause of autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD), primarily due to the defective maturation and surface expression of polycystin-1 (J Am Soc Nephrol, 2017). Pharmacologically, GANAB is targeted by iminosugars such as celgosivir and castanospermine, which are investigated for their antiviral properties—by preventing the folding of viral envelope proteins—and for their potential to modulate protein folding in various genetic disorders (PubChem CID 65362).

Other names

Glucosidase II subunit alphaAlpha-glucosidase 2G2ANNeutral alpha-glucosidaseGlucosidase II alpha subunitGANAB

Competitive inhibition of the alpha subunit of glucosidase II, preventing the removal of glucose residues from N-glycans and thereby disrupting the calnexin/calreticulin-mediated protein folding pathway (PubMed: 27230638).