Calnexin

Calnexin (CNX) is a 67kDa integral protein (that appears variously as a 90kDa, 80kDa or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER). It consists of a large (50 kDa) N-terminal calcium-binding lumenal domain, a single transmembrane helix and a short (90 residues), acidic cytoplasmic tail.

Function

Calnexin is a chaperone, characterized by assisting protein folding and quality control, ensuring that only properly folded and assembled proteins proceed further along the secretory pathway. It specifically acts to retain unfolded or unassembled N-linked glycoproteins in the ER. Calnexin binds only those N-glycoproteins that have GlcNAc2Man9Glc1 oligosaccharides. These monoglucosylated oligosaccharides result from the trimming of two glucose residues by the sequential action of two glucosidases, I and II. Glucosidase II can also remove the third and last glucose residue. If the glycoprotein is not properly folded, an enzyme called UGGT (for UDP-glucose:glycoprotein glucosyltransferase) will add the glucose residue back onto the oligosaccharide thus regenerating the glycoprotein's ability to bind to calnexin. The improperly-folded glycoprotein chain thus loiters in the ER, risking the encounter with MNS1 (alpha-mannosidase), which eventually sentences the underperforming glycoprotein to degradation by removing one of the nine mannose residues. If the protein is correctly translated, the chance of it being correctly folded before it encounters MNS1 is high.