Calnexin

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

Function
Calnexin is a chaperone, characterized by assisting is_associated_with::protein folding and quality control, ensuring that only properly folded and assembled proteins proceed further along the is_associated_with::secretory pathway. It specifically acts to retain unfolded or unassembled N-linked is_associated_with::glycoproteins in the ER. Calnexin binds only those N-is_associated_with::glycoproteins that have GlcNAc2Man9Glc1 is_associated_with::oligosaccharides. These monoglucosylated oligosaccharides result from the trimming of two glucose residues by the sequential action of two is_associated_with::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 is_associated_with::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 (is_associated_with::alpha-mannosidase), which eventually sentences the underperforming glycoprotein to degradation by removing its is_associated_with::mannose residue. If the protein is correctly translated, the chance of it being correctly folded before it encounters MNS1 is high.

Calnexin also functions as a chaperone for the folding of is_associated_with::MHC class I α-chain in the membrane of the ER. As newly synthesized MHC class I α-chains enter the endoplasmic reticulum, calnexin binds on to them retaining them in a partly folded state. After the β2-microglobulin binds to the MHC class I peptide-loading complex (PLC), is_associated_with::calreticulin and is_associated_with::ERp57 take over the job of chaperoning the MHC class I protein while the is_associated_with::tapasin links the complex to the is_associated_with::Transporter associated with antigen processing (TAP) complex. This association prepares the MHC class I for binding an antigen for presentation on the cell surface.

Cofactors
ATP and calcium ions are cofactors involved in substrate binding for calnexin.