Calnexin

CANX
Identifiers
AliasesCANX, CNX, IP90, P90, calnexin
External IDsOMIM: 114217 MGI: 88261 HomoloGene: 1324 GeneCards: CANX
Gene location (Human)
Chr.Chromosome 5 (human)[1]
Band5q35.3Start179,678,628 bp[1]
End179,730,925 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

821

12330

Ensembl

ENSG00000283777
ENSG00000127022

ENSMUSG00000020368

UniProt

P27824

P35564

RefSeq (mRNA)

NM_001024649
NM_001746

NM_001110499
NM_001110500
NM_007597

RefSeq (protein)

NP_001103969
NP_001103970
NP_031623

Location (UCSC)Chr 5: 179.68 – 179.73 MbChr 11: 50.29 – 50.33 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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. 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 one of the nine mannose residues. 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.[5] 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.

Cofactors

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

References

  1. 1 2 3 ENSG00000127022 GRCh38: Ensembl release 89: ENSG00000283777, ENSG00000127022 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020368 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Murphy K (2011). Janeway's Immunobiology (8th ed.). Oxford: Taylor & Francis. ISBN 978-0815342434.

Further reading

  • Benyair R, Ron E, Lederkremer GZ (2011). "Protein quality control, retention, and degradation at the endoplasmic reticulum". International Review of Cell and Molecular Biology. International Review of Cell and Molecular Biology. 292: 197–280. doi:10.1016/B978-0-12-386033-0.00005-0. ISBN 9780123860330. PMID 22078962.
  • Del Bem LE (Feb 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 (Aug 2004). "Protein folding and quality control in the endoplasmic reticulum". Current Opinion in Cell Biology. 16 (4): 343–9. doi:10.1016/j.ceb.2004.06.012. PMID 15261665. 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". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667. Check date values in: |year= / |date= mismatch (help)
  • Galvin K, Krishna S, Ponchel F, Frohlich M, Cummings DE, Carlson R, Wands JR, Isselbacher KJ, Pillai S, Ozturk M (Sep 1992). "The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene". Proceedings of the National Academy of Sciences of the United States of America. 89 (18): 8452–6. doi:10.1073/pnas.89.18.8452. PMC 49938. PMID 1326756.
  • 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 Chemistry. 269 (17): 12784–8. PMID 7513695.
  • 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". Electrophoresis. 15 (3–4): 482–90. doi:10.1002/elps.1150150166. PMID 8055875.
  • Tjoelker LW, Seyfried CE, Eddy RL, Byers MG, Shows TB, Calderon J, Schreiber RB, Gray PW (Mar 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 (Apr 1994). "The integrin chains beta 1 and alpha 6 associate with the chaperone calnexin prior to integrin assembly". The Journal of Biological Chemistry. 269 (16): 12263–8. PMID 8163531.
  • Rajagopalan S, Xu Y, Brenner MB (Jan 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 (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 Chemistry. 268 (13): 9585–92. PMID 8486646.
  • 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 Research. 222 (1): 77–83. doi:10.1006/excr.1996.0010. PMID 8549676.
  • 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 Chemistry. 271 (1): 97–103. doi:10.1074/jbc.271.1.97. PMID 8550632.
  • Devergne O, Hummel M, Koeppen H, Le Beau MM, Nathanson EC, Kieff E, Birkenbach M (Feb 1996). "A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes". Journal of Virology. 70 (2): 1143–53. PMC 189923. PMID 8551575.
  • Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
  • 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 Chemistry. 271 (16): 9660–5. doi:10.1074/jbc.271.16.9660. PMID 8621641.
  • Oliver JD, Hresko RC, Mueckler M, High S (Jun 1996). "The glut 1 glucose transporter interacts with calnexin and calreticulin". The Journal of Biological Chemistry. 271 (23): 13691–6. doi:10.1074/jbc.271.23.13691. PMID 8662691.
  • Li Y, Bergeron JJ, Luo L, Ou WJ, Thomas DY, Kang CY (Sep 1996). "Effects of inefficient cleavage of the signal sequence of HIV-1 gp 120 on its association with calnexin, folding, and intracellular transport". Proceedings of the National Academy of Sciences of the United States of America. 93 (18): 9606–11. doi:10.1073/pnas.93.18.9606. PMC 38475. PMID 8790377.
  • 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 Chemistry. 271 (44): 27509–16. doi:10.1074/jbc.271.44.27509. PMID 8910335.
  • Tatu U, Helenius A (Feb 1997). "Interactions between newly synthesized glycoproteins, calnexin and a network of resident chaperones in the endoplasmic reticulum". The Journal of Cell Biology. 136 (3): 555–65. doi:10.1083/jcb.136.3.555. PMC 2134297. PMID 9024687.
  • Wiest DL, Bhandoola A, Punt J, Kreibich G, McKean D, Singer A (Mar 1997). "Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of "ER-resident" molecular chaperones". Proceedings of the National Academy of Sciences of the United States of America. 94 (5): 1884–9. doi:10.1073/pnas.94.5.1884. PMC 20012. PMID 9050874.
  • Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
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