Calnexin

Identifiers Symbols CANX; CNX; IP90; P90 External IDs OMIM: 114217 MGI: 88261 HomoloGene: 1324 ChEMBL: 2719 GeneCards: CANX Gene

Gene Ontology
Molecular function calcium ion binding
protein binding
carbohydrate binding
unfolded protein binding
Cellular component endoplasmic reticulum
endoplasmic reticulum lumen
endoplasmic reticulum membrane
melanosome
integral to lumenal side of endoplasmic reticulum membrane
Biological process antigen processing and presentation of peptide antigen via MHC class I
protein folding
protein secretion
protein N-linked glycosylation via asparagine
antigen processing and presentation of exogenous peptide antigen via MHC class II
post-translational protein modification
cellular protein metabolic process
synaptic vesicle endocytosis
clathrin-mediated endocytosis
Sources: Amigo / QuickGO
RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 821 12330 Ensembl ENSG00000127022 ENSMUSG00000020368 UniProt P27824 P35564 RefSeq (mRNA) NM_001024649.1 NM_001110499.1 RefSeq (protein) NP_001019820.1 NP_001103969.1 Location (UCSC) Chr 5:
179.11 – 179.16 Mb Chr 11:
50.29 – 50.33 Mb PubMed search

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.

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 ER. Antibodies against calnexin can be used as markers for the ER in immmunofluorescence experiments.

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.

If the protein is correctly translated, the chance of it being correctly folded before it encounters MNS1 is high.

ATP and calcium ions 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.

Other articles related to "calnexin":

Calreticulin - Function
... A similar quality-control chaperone, calnexin, performs the same service for soluble proteins as does calreticulin ... Both proteins, Calnexin and calreticulin, have the function of binding to oligosaccharides containing terminal glucose residues, thereby targeting them for degradation ... will re-add glucose residues so that other Calreticulin/Calnexin can bind to these proteins and prevent them from proceeding to the Golgi ...
MHC Class I - Translocation and Peptide Loading
... that form a large multimeric complex consisting of TAP, tapasin, calreticulin, calnexin, and Erp57 ... Calnexin acts to stabilize the class I MHC α chains prior to β2m binding ... Following complete assembly of the MHC molecule, calnexin dissociates ...
CALR - Function
... A similar quality-control chaperone, calnexin, performs the same service for soluble proteins as does calreticulin ... Both proteins, Calnexin and calreticulin, have the function of binding to oligosaccharides containing terminal glucose residues, thereby targeting them for degradation ... residues so that other Calreticulin/Calnexin can bind to these proteins and prevent them from proceeding to the Golgi ...