Calnexin

Calnexin (CNX) is a 90kDa integral protein 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.

Calnexin is one of the chaperone molecules, which are characterized by their main function of assisting protein folding and quality control, ensuring that only properly folded and assembled proteins proceed further along the secretory pathway.

The function of calnexin is to retain unfolded or unassembled N-linked glycoproteins in the endoplasmic reticulum.

Calnexin binds only those N-glycoproteins that have GlcNAc2Man9Glc1 oligosaccharides.

Oligosaccharides with three sequential glucose residues are added to asparagine residues of the nascent proteins in the ER.

The monoglucosylated oligosaccharides that are recognized by calnexin 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.

ATP and Ca++ are two of the cofactors involved in substrate binding for calnexin.

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.

External links

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Further reading

PBB_Further_reading
citations =
*cite journal | author=Kleizen B, Braakman I |title=Protein folding and quality control in the endoplasmic reticulum. |journal=Curr. Opin. Cell Biol. |volume=16 |issue= 4 |pages= 343–9 |year= 2005 |pmid= 15261665 |doi= 10.1016/j.ceb.2004.06.012
*cite journal | author=Rasmussen HH, van Damme J, Puype M, "et al." |title=Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. |journal=Electrophoresis |volume=13 |issue= 12 |pages= 960–9 |year= 1993 |pmid= 1286667 |doi=
*cite journal | author=Galvin K, Krishna S, Ponchel F, "et al." |title=The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 18 |pages= 8452–6 |year= 1992 |pmid= 1326756 |doi=
*cite journal | author=Pind S, Riordan JR, Williams DB |title=Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. |journal=J. Biol. Chem. |volume=269 |issue= 17 |pages= 12784–8 |year= 1994 |pmid= 7513695 |doi=
*cite journal | author=Honoré B, Rasmussen HH, Celis A, "et al." |title=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. |journal=Electrophoresis |volume=15 |issue= 3-4 |pages= 482–90 |year= 1994 |pmid= 8055875 |doi=
*cite journal | author=Tjoelker LW, Seyfried CE, Eddy RL, "et al." |title=Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5. |journal=Biochemistry |volume=33 |issue= 11 |pages= 3229–36 |year= 1994 |pmid= 8136357 |doi=
*cite journal | author=Lenter M, Vestweber D |title=The integrin chains beta 1 and alpha 6 associate with the chaperone calnexin prior to integrin assembly. |journal=J. Biol. Chem. |volume=269 |issue= 16 |pages= 12263–8 |year= 1994 |pmid= 8163531 |doi=
*cite journal | author=Rajagopalan S, Xu Y, Brenner MB |title=Retention of unassembled components of integral membrane proteins by calnexin. |journal=Science |volume=263 |issue= 5145 |pages= 387–90 |year= 1994 |pmid= 8278814 |doi=
*cite journal | author=David V, Hochstenbach F, Rajagopalan S, Brenner MB |title=Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin). |journal=J. Biol. Chem. |volume=268 |issue= 13 |pages= 9585–92 |year= 1993 |pmid= 8486646 |doi=
*cite journal | author=Bellovino D, Morimoto T, Tosetti F, Gaetani S |title=Retinol binding protein and transthyretin are secreted as a complex formed in the endoplasmic reticulum in HepG2 human hepatocarcinoma cells. |journal=Exp. Cell Res. |volume=222 |issue= 1 |pages= 77–83 |year= 1996 |pmid= 8549676 |doi= 10.1006/excr.1996.0010
*cite journal | author=Otteken A, Moss B |title=Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin. |journal=J. Biol. Chem. |volume=271 |issue= 1 |pages= 97–103 |year= 1996 |pmid= 8550632 |doi=
*cite journal | author=Devergne O, Hummel M, Koeppen H, "et al." |title=A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes. |journal=J. Virol. |volume=70 |issue= 2 |pages= 1143–53 |year= 1996 |pmid= 8551575 |doi=
*cite journal | author=Andersson B, Wentland MA, Ricafrente JY, "et al." |title=A "double adaptor" method for improved shotgun library construction. |journal=Anal. Biochem. |volume=236 |issue= 1 |pages= 107–13 |year= 1996 |pmid= 8619474 |doi= 10.1006/abio.1996.0138
*cite journal | author=van Leeuwen JE, Kearse KP |title=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. |journal=J. Biol. Chem. |volume=271 |issue= 16 |pages= 9660–5 |year= 1996 |pmid= 8621641 |doi=
*cite journal | author=Oliver JD, Hresko RC, Mueckler M, High S |title=The glut 1 glucose transporter interacts with calnexin and calreticulin. |journal=J. Biol. Chem. |volume=271 |issue= 23 |pages= 13691–6 |year= 1996 |pmid= 8662691 |doi=
*cite journal | author=Li Y, Bergeron JJ, Luo L, "et al." |title=Effects of inefficient cleavage of the signal sequence of HIV-1 gp 120 on its association with calnexin, folding, and intracellular transport. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 18 |pages= 9606–11 |year= 1996 |pmid= 8790377 |doi=
*cite journal | author=Trombetta ES, Simons JF, Helenius A |title=Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit. |journal=J. Biol. Chem. |volume=271 |issue= 44 |pages= 27509–16 |year= 1996 |pmid= 8910335 |doi=
*cite journal | author=Tatu U, Helenius A |title=Interactions between newly synthesized glycoproteins, calnexin and a network of resident chaperones in the endoplasmic reticulum. |journal=J. Cell Biol. |volume=136 |issue= 3 |pages= 555–65 |year= 1997 |pmid= 9024687 |doi=
*cite journal | author=Wiest DL, Bhandoola A, Punt J, "et al." |title=Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of "ER-resident" molecular chaperones. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 5 |pages= 1884–9 |year= 1997 |pmid= 9050874 |doi=
*cite journal | author=Yu W, Andersson B, Worley KC, "et al." |title=Large-scale concatenation cDNA sequencing. |journal=Genome Res. |volume=7 |issue= 4 |pages= 353–8 |year= 1997 |pmid= 9110174 |doi=

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