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 its 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 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), calreticulin and ERp57 take over the job of chaperoning the MHC class I protein while the tapasin links the complex to the Transporter associated with antigen processing (TAP) complex. This association prepares the MHC class I for binding an antigen for presentation on the cell surface.
Kleizen B, Braakman I (Aug 2004). "Protein folding and quality control in the endoplasmic reticulum". Current Opinion in Cell Biology16 (4): 343–9. doi:10.1016/j.ceb.2004.06.012. PMID15261665.Check date values in: |year= / |date= mismatch (help)
Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (Dec 1992). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis13 (12): 960–9. doi:10.1002/elps.11501301199. PMID1286667.Check date values in: |year= / |date= mismatch (help)
Pind S, Riordan JR, Williams DB (Apr 1994). "Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator". The Journal of Biological Chemistry269 (17): 12784–8. PMID7513695.CS1 maint: Date and year (link)
Honoré B, Rasmussen HH, Celis A, Leffers H, Madsen P, Celis JE (1994). "The molecular chaperones HSP28, GRP78, endoplasmin, and calnexin exhibit strikingly different levels in quiescent keratinocytes as compared to their proliferating normal and transformed counterparts: cDNA cloning and expression of calnexin". Electrophoresis15 (3-4): 482–90. doi:10.1002/elps.1150150166. PMID8055875.
Tjoelker LW, Seyfried CE, Eddy RL, Byers MG, Shows TB, Calderon J et al. (Mar 1994). "Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5". Biochemistry33 (11): 3229–36. doi:10.1021/bi00177a013. PMID8136357.CS1 maint: Date and year (link)
Lenter M, Vestweber D (Apr 1994). "The integrin chains beta 1 and alpha 6 associate with the chaperone calnexin prior to integrin assembly". The Journal of Biological Chemistry269 (16): 12263–8. PMID8163531.CS1 maint: Date and year (link)
Rajagopalan S, Xu Y, Brenner MB (Jan 1994). "Retention of unassembled components of integral membrane proteins by calnexin". Science (New York, N.Y.)263 (5145): 387–90. doi:10.1126/science.8278814. PMID8278814.CS1 maint: Date and year (link)
David V, Hochstenbach F, Rajagopalan S, Brenner MB (May 1993). "Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin)". The Journal of Biological Chemistry268 (13): 9585–92. PMID8486646.CS1 maint: Date and year (link)
Bellovino D, Morimoto T, Tosetti F, Gaetani S (Jan 1996). "Retinol binding protein and transthyretin are secreted as a complex formed in the endoplasmic reticulum in HepG2 human hepatocarcinoma cells". Experimental Cell Research222 (1): 77–83. doi:10.1006/excr.1996.0010. PMID8549676.CS1 maint: Date and year (link)
Otteken A, Moss B (Jan 1996). "Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin". The Journal of Biological Chemistry271 (1): 97–103. doi:10.1074/jbc.271.1.97. PMID8550632.CS1 maint: Date and year (link)
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID8619474.CS1 maint: Date and year (link)
van Leeuwen JE, Kearse KP (Apr 1996). "Calnexin associates exclusively with individual CD3 delta and T cell antigen receptor (TCR) alpha proteins containing incompletely trimmed glycans that are not assembled into multisubunit TCR complexes". The Journal of Biological Chemistry271 (16): 9660–5. doi:10.1074/jbc.271.16.9660. PMID8621641.CS1 maint: Date and year (link)
Oliver JD, Hresko RC, Mueckler M, High S (Jun 1996). "The glut 1 glucose transporter interacts with calnexin and calreticulin". The Journal of Biological Chemistry271 (23): 13691–6. doi:10.1074/jbc.271.23.13691. PMID8662691.CS1 maint: Date and year (link)
Trombetta ES, Simons JF, Helenius A (Nov 1996). "Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit". The Journal of Biological Chemistry271 (44): 27509–16. doi:10.1074/jbc.271.44.27509. PMID8910335.CS1 maint: Date and year (link)