Calnexin

Calnexin
Lumenal domain of calnexin from PDB: 1JHN​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1jhn
Identifiers
Symbols	CANX ; CNX; IP90; P90
External IDs	OMIM: 114217 MGI: 88261 HomoloGene: 1324 ChEMBL: 2719 GeneCards: CANX Gene
Gene ontology Molecular function • glycoprotein binding • calcium ion binding • protein binding • carbohydrate binding • apolipoprotein binding • ionotropic glutamate receptor binding • poly(A) RNA binding • unfolded protein binding Cellular component • endoplasmic reticulum • endoplasmic reticulum lumen • endoplasmic reticulum membrane • smooth endoplasmic reticulum • rough endoplasmic reticulum • ribosome • membrane • axon • dendrite cytoplasm • melanosome • neuronal cell body • dendritic spine • myelin sheath • protein complex • ER-mitochondrion membrane contact site • extracellular exosome • integral component of lumenal side of endoplasmic reticulum membrane Biological process • antigen processing and presentation of peptide antigen via MHC class I • protein folding • aging • protein secretion • protein N-linked glycosylation via asparagine • antigen processing and presentation of exogenous peptide antigen via MHC class II • protein folding in endoplasmic reticulum • post-translational protein modification • cellular protein metabolic process • synaptic vesicle endocytosis • chaperone-mediated protein folding • 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	NM_001110499
RefSeq (protein)	NP_001019820	NP_001103969
Location (UCSC)	Chr 5: 179.68 – 179.73 Mb	Chr 11: 50.29 – 50.33 Mb
PubMed search	[1]	[2]

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. 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.

External links

• Calnexin at the US National Library of Medicine Medical Subject Headings (MeSH)