UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1)

UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) is a soluble enzyme resident in the endoplasmic reticulum (ER) that acts as a folding sensor in the glycoprotein quality control system. It recognizes misfolded or incompletely folded glycoproteins and catalyzes the transfer of a glucose residue from UDP-glucose to specific N-glycans on these proteins. This reglucosylation tags the glycoprotein for further interaction with ER lectin chaperones (calnexin and calreticulin), facilitating ensuing cycles of folding or targeting for degradation if refolding fails. UGGT1 is essential for cellular proteostasis, impacting diseases involving protein misfolding (e.g., some storage and neurodegenerative diseases) and the proper function of antigen presentation pathways (such as MHC class I peptide loading). In mammals, two isoforms exist (UGGT1 and UGGT2), with UGGT1 predominating as the key regulator for complex and plasma membrane-bound glycoproteins. Deficiency or dysfunction of UGGT1 can impair glycoprotein maturation, solubility, and ER stress responses, underlying its importance as an ER quality control checkpoint enzyme.

Other names

UDP-glucose glycoprotein glucosyltransferase 1UGGT1UDP-glucose:glycoprotein glucosyltransferaseUGGTUGT1UGTRhUGT1HUGT1UGCGL1UDP--Glc:glycoprotein glucosyltransferaseUDP-glucose ceramide glucosyltransferase-like 1

For hypothetical drugs targeting UGGT1, expected mechanisms would include: inhibition of glycoprotein reglucosylation, modulation of ER quality control, or alteration of calnexin/calreticulin chaperone cycling