UGGT, or ( UDP)- glucose: glycoprotein glucosyltransferase is a soluble enzyme resident in the lumen of the endoplasmic reticulum (ER). UGGT is about 170 kDa consisting of two structurally independent domains: a variable N-terminal domain of ~1200 amino acids thought to participate in sensing protein folding and a highly conserved C-terminal catalytic domain of ~300 amino acids. The main function of UGGT is to recognize misfolded glycoproteins and transfer a glucose (Glc) monomer (monoglucosylate) to the terminal mannose on the glycoprotein. It uses UDP-Glc as the glycosyl donor and requires calcium ions for its activity.
UGGT is part of the ER quality control system of glycoprotein folding and its activity increases the potential for correctly folded glycoproteins. The main proteins involved in the ER quality control system are UGGT, the ER lectin chaperones ( calnexin and calreticulin), and glucosidase II. UGGT first recognize the incompletely folded glycoprotein and monoglucosylate it. The lectins, calnexin and calreticulin, have high affinities for monoglucosylated proteins and these chaperones may attempt to assist in folding of the misfolded protein. Subsequently, glucosidase II will deglucosylate the glycoprotein. If the glycoprotein is still misfolded, UGGT will monoglycosylate it and allow the glycoprotein to go through the cycle again.
Currently, it is unclear how UGGT recognize misfolded glycoprotein. It has been proposed that UGGT may bind to exposed hydrophobic stretches, a characteristic feature of misfolded proteins.