Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A (STT3A)

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A is the primary catalytic subunit of the oligosaccharyltransferase (OST) complex, which resides in the endoplasmic reticulum (ER) membrane (UniProt P46977). It is specifically responsible for co-translational N-glycosylation, a process where a pre-assembled oligosaccharide is transferred to the asparagine residue of a nascent polypeptide as it is being synthesized (PubMed: 25417110). This modification is essential for the correct folding, stability, and biological activity of a vast majority of secretory and membrane proteins. Mutations in the STT3A gene lead to congenital disorders of glycosylation (CDG-Iv), which manifest as severe developmental delays and neurological impairments (PubMed: 24532530). In therapeutic research, STT3A is targeted by small molecules like NGI-1 to disrupt the glycosylation of oncogenic receptors or viral glycoproteins, thereby inhibiting cancer progression or viral replication (PubMed: 27524445). However, because N-glycosylation is a fundamental cellular process, pharmacological targeting of STT3A carries a high risk of off-target toxicity and ER stress-induced cell death.

Other names

STT3-AOligosaccharyltransferase subunit STT3AIntegral membrane protein 1ITM1BWSSTT3A-OST

Inhibition of the catalytic subunit of the oligosaccharyltransferase complex to prevent the transfer of glycan chains to nascent polypeptides.