The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CANX  -  calnexin

Homo sapiens

Synonyms: CNX, Calnexin, IP90, Major histocompatibility complex class I antigen-binding protein p88, P90, ...


Calnexin and Calreticulin are two chaperons in the Endoplasmic Reticulum, and they mediate the folding of all the proteins in the secretory pathway.

Proteins in the secretory pathway are synthesized by a ribosome attached to the ER membrane and immediately imported inside the ER. The folding of these protein happens in the ER, and a key signal in this process are the glycans attached co-translationally to the protein.


Calnexin is a type I transmembrane protein [1], while Calreticulin is soluble.



Disease relevance of CANX


Psychiatry related information on CANX


High impact information on CANX

  • Further deglucosylation of the oligosaccharides by glucosidase II liberates glycoproteins from their calnexin/calreticulin anchors [8].
  • Calnexin, an endoplasmic reticulum transmembrane protein, represents a new type of molecular chaperone that selectively associates in a transient fashion with newly synthesized monomeric glycoproteins in HepG2 cells [9].
  • At least two main chaperone classes, BiP and calnexin/calreticulin, are active in ER quality control [10].
  • More than one glycan is needed for ER glucosidase II to allow entry of glycoproteins into the calnexin/calreticulin cycle [11].
  • Consistent with a requirement for multiple glycans to activate GII, pancreatic RNase in live cells needed more than one glycan to enter the Cnx/Crt cycle [11].

Chemical compound and disease context of CANX


Biological context of CANX


Anatomical context of CANX

  • In a beta2-microglobulin (beta2m)-negative mouse cell line, S3, ER-60-calnexin-heavy chain complexes are shown to bind to TAP, suggesting that beta2m is not required for the association of MHC class I heavy chains with TAP [20].
  • Structural fidelity is monitored by endoplasmic reticulum (ER) quality control involving the molecular chaperone calnexin [2].
  • However, in a T cell line that cannot assemble a complete T cell receptor because it lacks the alpha subunit, the unassembled T cell receptor beta chains, which are retained in the ER, remain associated with IP90 throughout a prolonged chase time period [21].
  • Calnexin interaction with N-glycosylation mutants of a polytopic membrane glycoprotein, the human erythrocyte anion exchanger 1 (band 3) [18].
  • An association of calnexin with truncated versions of N-glycosylated AE1 was detected after release of the nascent chains from ribosomes with puromycin [18].

Associations of CANX with chemical compounds

  • An inhibitor of glucose trimming, castanospermine (CST), abolished binding to Cnx/Crt but also unexpectedly accelerated receptor homodimerization resulting in misfolded oligomeric proreceptors whose processing was delayed and cell surface expression was also decreased by approximately 30% [16].
  • The glut 1 glucose transporter interacts with calnexin and calreticulin [22].
  • Based upon coimmunoprecipitation and cosedimentation through glycerol density gradients, newly synthesized wild-type and delta F508 mutant CFTRs associated specifically with calnexin, the calcium-binding transmembrane chaperone of the ER [17].
  • Ca(2+) homeostasis and ER morphology were unaffected by the lack of calnexin, but ER stress-induced Bap31 cleavage was significantly inhibited [19].
  • RESULTS: Calreticulin and calsequestrin (the two major calcium storage proteins of somatic cells), two types of calcium release receptors, the inositol trisphosphate and ryanodine receptors (InsP(3)R-2, RyRs-1,2,3), and the molecular chaperone, calnexin, were identified in all investigated cell types [23].
  • We show that calnexin interacts with the receptors via two distinct mechanisms, glycan-dependent and glycan-independent, which may underlie the multiple effects (ER retention and surface trafficking) of calnexin on receptor expression [24].

Physical interactions of CANX

  • Immunoprecipitation experiments revealed that Bap31 forms complexes with calnexin, which may play a role in apoptosis [19].
  • In this general way, CRT shares certain functional properties with the structurally homologous transmembrane calcium-binding endoplasmic reticulum protein calnexin [25].
  • Calnexin Delta 185-520 interacted with CFTR directly, and was secreted into the extracellular compartment over time [26].
  • Conditions that induce the calnexin "polypeptide-binding" conformation also induce self-association of calnexin if the concentration is sufficiently high; however, calnexin dimerization/oligomerization per se is not essential for polypeptide substrate binding [27].
  • Calnexin and other factors that alter translocation affect the rapid binding of ubiquitin to apoB in the Sec61 complex [28].

Co-localisations of CANX


Regulatory relationships of CANX


Other interactions of CANX

  • Together, these studies demonstrate a chaperone function for Cnx/Crt in HIR folding in vivo and also provide evidence that folding efficiency and homodimerization are counterbalanced [16].
  • A few of the positionally mapped genes in the 5q35 region that may potentially be involved in the etiology of this condition are CANX, FGFR4, HK3, and hnRPH1 [33].
  • Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin [2].
  • The formation of at least one of the disulfide bonds in the CD1d heavy chain is coupled to its glucose trimming-dependent association with ERp57, calnexin, and calreticulin [34].
  • The results show that the interaction of calnexin with the polytopic membrane glycoprotein AE1 was dependent on the presence but not the location of the oligosaccharide [18].

Analytical, diagnostic and therapeutic context of CANX

  • Following immunoprecipitation with an anticalnexin antiserum, a cross-linker-independent association was observed between GT155 and calnexin [22].
  • In the present study, we compared melanoma lesions representing different stages of tumor progression with regard to the expression of calnexin and calreticulin in tumor cells by means of immunohistochemistry [5].
  • Dissection of the degradation process revealed that upon release from calnexin, extensively oxidized BACE457 transiently entered in disulfide-bonded complexes associated with the lumenal chaperones BiP and protein disulfide isomerase (PDI) before unfolding and dislocation into the cytosol for degradation [35].
  • In Calu-3 airway cells, immunofluorescence colocalized Csp with calnexin in the endoplasmic reticulum and with CFTR at the apical membrane domain [36].
  • By cell fractionation, surface rTPO fractionated distinctly from internal pools of TPO (that co-fractionate with calnexin), yet surface TPO molecules remained endoglycosidase H (endo H)-sensitive [37].


  1. essentials of glycobiology. WikiGenes. Article
  2. Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Farinha, C.M., Amaral, M.D. Mol. Cell. Biol. (2005) [Pubmed]
  3. Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin. Otteken, A., Moss, B. J. Biol. Chem. (1996) [Pubmed]
  4. Roles of calreticulin and calnexin during mucin synthesis in LS180 and HT29/A1 human colonic adenocarcinoma cells. McCool, D.J., Okada, Y., Forstner, J.F., Forstner, G.G. Biochem. J. (1999) [Pubmed]
  5. Differential downregulation of endoplasmic reticulum-residing chaperones calnexin and calreticulin in human metastatic melanoma. Dissemond, J., Busch, M., Kothen, T., Mörs, J., Weimann, T.K., Lindeke, A., Goos, M., Wagner, S.N. Cancer Lett. (2004) [Pubmed]
  6. Consequences of ERp57 deletion on oxidative folding of obligate and facultative clients of the calnexin cycle. Soldà, T., Garbi, N., Hämmerling, G.J., Molinari, M. J. Biol. Chem. (2006) [Pubmed]
  7. Distinctive somatosensory evoked potential features in obsessive-compulsive disorder. Shagass, C., Roemer, R.A., Straumanis, J.J., Josiassen, R.C. Biol. Psychiatry (1984) [Pubmed]
  8. Protein glucosylation and its role in protein folding. Parodi, A.J. Annu. Rev. Biochem. (2000) [Pubmed]
  9. Association of folding intermediates of glycoproteins with calnexin during protein maturation. Ou, W.J., Cameron, P.H., Thomas, D.Y., Bergeron, J.J. Nature (1993) [Pubmed]
  10. Protein folding and quality control in the endoplasmic reticulum. Kleizen, B., Braakman, I. Curr. Opin. Cell Biol. (2004) [Pubmed]
  11. More than one glycan is needed for ER glucosidase II to allow entry of glycoproteins into the calnexin/calreticulin cycle. Deprez, P., Gautschi, M., Helenius, A. Mol. Cell (2005) [Pubmed]
  12. Insights into the quaternary association of proteins through structure graphs: a case study of lectins. Brinda, K.V., Surolia, A., Vishveshwara, S. Biochem. J. (2005) [Pubmed]
  13. Trimming and readdition of glucose to N-linked oligosaccharides determines calnexin association of a substrate glycoprotein in living cells. Cannon, K.S., Helenius, A. J. Biol. Chem. (1999) [Pubmed]
  14. Processing by endoplasmic reticulum mannosidases partitions a secretion-impaired glycoprotein into distinct disposal pathways. Cabral, C.M., Choudhury, P., Liu, Y., Sifers, R.N. J. Biol. Chem. (2000) [Pubmed]
  15. Target cell cyclophilin A modulates human immunodeficiency virus type 1 infectivity. Sokolskaja, E., Sayah, D.M., Luban, J. J. Virol. (2004) [Pubmed]
  16. Folding of insulin receptor monomers is facilitated by the molecular chaperones calnexin and calreticulin and impaired by rapid dimerization. Bass, J., Chiu, G., Argon, Y., Steiner, D.F. J. Cell Biol. (1998) [Pubmed]
  17. Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. Pind, S., Riordan, J.R., Williams, D.B. J. Biol. Chem. (1994) [Pubmed]
  18. Calnexin interaction with N-glycosylation mutants of a polytopic membrane glycoprotein, the human erythrocyte anion exchanger 1 (band 3). Popov, M., Reithmeier, R.A. J. Biol. Chem. (1999) [Pubmed]
  19. Calnexin deficiency and endoplasmic reticulum stress-induced apoptosis. Zuppini, A., Groenendyk, J., Cormack, L.A., Shore, G., Opas, M., Bleackley, R.C., Michalak, M. Biochemistry (2002) [Pubmed]
  20. ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly. Lindquist, J.A., Jensen, O.N., Mann, M., Hämmerling, G.J. EMBO J. (1998) [Pubmed]
  21. Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin). David, V., Hochstenbach, F., Rajagopalan, S., Brenner, M.B. J. Biol. Chem. (1993) [Pubmed]
  22. The glut 1 glucose transporter interacts with calnexin and calreticulin. Oliver, J.D., Hresko, R.C., Mueckler, M., High, S. J. Biol. Chem. (1996) [Pubmed]
  23. Calcium-binding proteins and calcium-release channels in human maturing oocytes, pronuclear zygotes and early preimplantation embryos. Balakier, H., Dziak, E., Sojecki, A., Librach, C., Michalak, M., Opas, M. Hum. Reprod. (2002) [Pubmed]
  24. D1 and D2 dopamine receptor expression is regulated by direct interaction with the chaperone protein calnexin. Free, R.B., Hazelwood, L.A., Cabrera, D.M., Spalding, H.N., Namkung, Y., Rankin, M.L., Sibley, D.R. J. Biol. Chem. (2007) [Pubmed]
  25. Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase. Nauseef, W.M., McCormick, S.J., Clark, R.A. J. Biol. Chem. (1995) [Pubmed]
  26. Calnexin Delta 185-520 partially reverses the misprocessing of the Delta F508 cystic fibrosis transmembrane conductance regulator. Okiyoneda, T., Wada, I., Jono, H., Shuto, T., Yoshitake, K., Nakano, N., Nagayama, S., Harada, K., Isohama, Y., Miyata, T., Kai, H. FEBS Lett. (2002) [Pubmed]
  27. Polypeptide substrate recognition by calnexin requires specific conformations of the calnexin protein. Thammavongsa, V., Mancino, L., Raghavan, M. J. Biol. Chem. (2005) [Pubmed]
  28. Calnexin and other factors that alter translocation affect the rapid binding of ubiquitin to apoB in the Sec61 complex. Chen, Y., Le Cahérec, F., Chuck, S.L. J. Biol. Chem. (1998) [Pubmed]
  29. Cytoplasmic confinement of breast cancer resistance protein (BCRP/ABCG2) as a novel mechanism of adaptation to short-term folate deprivation. Ifergan, I., Jansen, G., Assaraf, Y.G. Mol. Pharmacol. (2005) [Pubmed]
  30. Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Olson, D.C., Marechal, V., Momand, J., Chen, J., Romocki, C., Levine, A.J. Oncogene (1993) [Pubmed]
  31. Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat. Norez, C., Noel, S., Wilke, M., Bijvelds, M., Jorna, H., Melin, P., DeJonge, H., Becq, F. FEBS Lett. (2006) [Pubmed]
  32. Calnexin influences folding of human class I histocompatibility proteins but not their assembly with beta 2-microglobulin. Tector, M., Salter, R.D. J. Biol. Chem. (1995) [Pubmed]
  33. Mapping of primary congenital lymphedema to the 5q35.3 region. Evans, A.L., Brice, G., Sotirova, V., Mortimer, P., Beninson, J., Burnand, K., Rosbotham, J., Child, A., Sarfarazi, M. Am. J. Hum. Genet. (1999) [Pubmed]
  34. Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain. Kang, S.J., Cresswell, P. J. Biol. Chem. (2002) [Pubmed]
  35. Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER. Molinari, M., Galli, C., Piccaluga, V., Pieren, M., Paganetti, P. J. Cell Biol. (2002) [Pubmed]
  36. Cysteine string protein interacts with and modulates the maturation of the cystic fibrosis transmembrane conductance regulator. Zhang, H., Peters, K.W., Sun, F., Marino, C.R., Lang, J., Burgoyne, R.D., Frizzell, R.A. J. Biol. Chem. (2002) [Pubmed]
  37. Intracellular trafficking of thyroid peroxidase to the cell surface. Kuliawat, R., Ramos-Castañeda, J., Liu, Y., Arvan, P. J. Biol. Chem. (2005) [Pubmed]
WikiGenes - Universities