UGGT1

UGGT1 Full Name

UDP-glucose glycoprotein glucosyltransferase 1

UGGT1 Introduction

UGGT1 encodes UDP-glucose glycoprotein glucosyltransferase 1, an endoplasmic reticulum (ER)-resident enzyme that serves as the central folding sensor of the calnexin/calreticulin quality-control cycle. Newly synthesized glycoproteins acquire N-linked glycans that are progressively trimmed by ER glucosidases to expose a single terminal glucose, a modification specifically recognized by the lectin chaperones calnexin and calreticulin. As the client protein folds, the final glucose is removed and the glycoprotein is released toward the secretory pathway. UGGT1 continuously monitors these released glycoproteins for incomplete folding and acts selectively only on polypeptides that have not yet reached their native conformation. This discrimination depends on the enzyme's capacity to recognize exposed regions of the unfolded polypeptide backbone rather than the glycan itself, enabling the system to distinguish native from non-native clients with high fidelity and to initiate retention before faulty proteins can escape the ER. Loss of UGGT1 activity disrupts this cycle and contributes to the accumulation of misfolded proteins associated with certain ER storage disorders.

Figure 1. Glycoprotein quality control system in the endoplasmic reticulum. (Source: Kuribara T, et al. 2021)

When UGGT1 identifies a misfolded glycoprotein, it catalyzes the transfer of a single glucose residue from UDP-glucose back onto the N-glycan, regenerating the monoglucosylated structure that re-engages calnexin and calreticulin. This reglucosylation step retains the substrate in the ER for additional folding attempts and prevents the premature export of incompletely folded proteins. Studies in mammalian cells demonstrate that reglucosylation by UGGT1 can delay the secretion of glycoproteins without altering their eventual degradation, indicating that the enzyme fine-tunes the balance between retention and disposal. Beyond its canonical transferase activity, comparative analyses show that the two mammalian glucosyltransferases, UGGT1 and UGGT2, recognize distinct classes of client proteins with largely non-overlapping specificity, and that UGGT1 can also exert a foldase-like effect that promotes substrate solubility in the ER. The enzyme's N-terminal domain harbors the misfold-detection sensor, whereas the C-terminal domain carries the glucosyltransferase catalytic site. These properties establish UGGT1 as a pivotal checkpoint linking protein folding, ER retention, and cellular quality control.

Alternate Names for UGGT1

UGGT1; UDP-glucose glycoprotein glucosyltransferase 1; UGT1; HUGT1; UGCGL1; UDP-glucose:glycoprotein glucosyltransferase 1; UDP--Glc:glycoprotein glucosyltransferase; UDP-glucose ceramide glucosyltransferase-like 1;

• 1. Kuribara T, et al. Glycan structure-based perspectives on the entry and release of glycoproteins in the calnexin/calreticulin cycle. Carbohydr Res. 2021 Apr;502:108273.
  2. annous A, et al. Reglucosylation by UDP-glucose:glycoprotein glucosyltransferase 1 delays glycoprotein secretion but not degradation. Mol Biol Cell. 2015 Feb 1;26(3):390-405.