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.
Calnexin 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 alpha chain in the membrane of the ER. After folding is completed Calnexin is replaced by Calreticulin, which assists in further assembly of MHC class I.
Uses in molecular biology
Antibodies against calnexin can be used as markers for the ER in immmunofluorescence experiments. [1]
Cofactors
ATP and calcium ions are cofactors involved in substrate binding for calnexin.
External links
- Calnexin at the US National Library of Medicine Medical Subject Headings (MeSH)
References
Further reading
- Del Bem LEV (2011). "The evolutionary history of calreticulin and calnexin genes in green plants.". Genetica 139 (2): 225–9. doi:10.1007/s10709-010-9544-y. PMID 21222018.
- Kleizen B, Braakman I (2005). "Protein folding and quality control in the endoplasmic reticulum.". Curr. Opin. Cell Biol. 16 (4): 343–9. doi:10.1016/j.ceb.2004.06.012. PMID 15261665.
- Rasmussen HH, van Damme J, Puype M, et al. (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.". Electrophoresis 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667.
- Galvin K, Krishna S, Ponchel F, et al. (1992). "The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene". Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8452–6. doi:10.1073/pnas.89.18.8452. PMC 49938. PMID 1326756.
- Pind S, Riordan JR, Williams DB (1994). "Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator". J. Biol. Chem. 269 (17): 12784–8. PMID 7513695.
- Honoré B, Rasmussen HH, Celis A, et al. (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". Electrophoresis 15 (3–4): 482–90. doi:10.1002/elps.1150150166. PMID 8055875.
- Tjoelker LW, Seyfried CE, Eddy RL, et al. (1994). "Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5". Biochemistry 33 (11): 3229–36. doi:10.1021/bi00177a013. PMID 8136357.
- Lenter M, Vestweber D (1994). "The integrin chains beta 1 and alpha 6 associate with the chaperone calnexin prior to integrin assembly". J. Biol. Chem. 269 (16): 12263–8. PMID 8163531.
- Rajagopalan S, Xu Y, Brenner MB (1994). "Retention of unassembled components of integral membrane proteins by calnexin". Science 263 (5145): 387–90. doi:10.1126/science.8278814. PMID 8278814.
- David V, Hochstenbach F, Rajagopalan S, Brenner MB (1993). "Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin)". J. Biol. Chem. 268 (13): 9585–92. PMID 8486646.
- Bellovino D, Morimoto T, Tosetti F, Gaetani S (1996). "Retinol binding protein and transthyretin are secreted as a complex formed in the endoplasmic reticulum in HepG2 human hepatocarcinoma cells". Exp. Cell Res. 222 (1): 77–83. doi:10.1006/excr.1996.0010. PMID 8549676.
- Otteken A, Moss B (1996). "Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin". J. Biol. Chem. 271 (1): 97–103. doi:10.1074/jbc.271.1.97. PMID 8550632.
- Devergne O, Hummel M, Koeppen H, et al. (1996). "A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes". J. Virol. 70 (2): 1143–53. PMC 189923. PMID 8551575.
- Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- van Leeuwen JE, Kearse KP (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". J. Biol. Chem. 271 (16): 9660–5. doi:10.1074/jbc.271.16.9660. PMID 8621641.
- Oliver JD, Hresko RC, Mueckler M, High S (1996). "The glut 1 glucose transporter interacts with calnexin and calreticulin". J. Biol. Chem. 271 (23): 13691–6. doi:10.1074/jbc.271.23.13691. PMID 8662691.
- Li Y, Bergeron JJ, Luo L, et al. (1996). "Effects of inefficient cleavage of the signal sequence of HIV-1 gp 120 on its association with calnexin, folding, and intracellular transport". Proc. Natl. Acad. Sci. U.S.A. 93 (18): 9606–11. doi:10.1073/pnas.93.18.9606. PMC 38475. PMID 8790377.
- Trombetta ES, Simons JF, Helenius A (1996). "Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit". J. Biol. Chem. 271 (44): 27509–16. doi:10.1074/jbc.271.44.27509. PMID 8910335.
- Tatu U, Helenius A (1997). "Interactions between Newly Synthesized Glycoproteins, Calnexin and a Network of Resident Chaperones in the Endoplasmic Reticulum". J. Cell Biol. 136 (3): 555–65. doi:10.1083/jcb.136.3.555. PMC 2134297. PMID 9024687.
- Wiest DL, Bhandoola A, Punt J, et al. (1997). "Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of "ER-resident" molecular chaperones". Proc. Natl. Acad. Sci. U.S.A. 94 (5): 1884–9. doi:10.1073/pnas.94.5.1884. PMC 20012. PMID 9050874.
- Yu W, Andersson B, Worley KC, et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
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