ER Quality Control Compartment (ERQC) Authored: Dall'Olio, GM, 2009-11-10 Edited: Jassal, B, 2010-07-02 Proteins that are released from the CNX or CRT complex with folding defects accumulate in a compartment of the ER called ERQC (Kamhi-Nesher S et al 2001). Here, the enzymes UGGG1 or UGGG2 are able to recognize glycoproteins with minor folding process and re-add the glucose on the alpha,1,3 branch; this is a signal for the transport of these glycoproteins back to the ER, where they can interact again with CNX or CRT in order to achieve a correct folding. At the same time that the glycoprotein is in the ERQC, the enzyme ER mannosidase I progressively removes the mannoses in position 1A, 2A, B, C on the N-glycans; when the mannose on 1A is trimmed, UGGG1/UGGG2 is no longer able to re-add the glucose, and therefore the protein is destined for degradation.<br>For years it has been thought that the removal of the mannose in position B of the N-glycan was the signal to direct proteins to degradation. However, this mechanism has been described better by Avezov et al (Avezov V et al, 2008) and it has been demonstrated that even glycoproteins with Man8 or Man7 glycans can be re-glucosylated and interact again with CNX or CRT. For a review on this topic, see Lederkremer GZ, 2009 and Määttänen P et al, 2010. Pubmed11408579 Pubmed18003979 Pubmed19616933 Pubmed20347046 Reactome Database ID Release 43901032 Reactome, http://www.reactome.org ReactomeREACT_25091 Reviewed: Gagneux, P, 2010-11-18 PathwayStep3140 PathwayStep3141 PathwayStep3142 PathwayStep3143 PathwayStep3144 PathwayStep3139 PathwayStep3138 Glycoproteins with lesser folding defects get transported back to the ER and the CNX/CRT complex Glycoproteins with major folding defects are sent to degradation by EDEMs Re-addition of a glucose on the alpha 1,3 branch Trimming of the second mannose on the A branch Trimming of the first mannose on the A branch Trimming of the terminal mannose on the C branch Trimming of the terminal mannose on the B branch