Calnexin (CANX)
The protein contains 592 amino acids for an estimated molecular weight of 67568 Da.
Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Aging
Antigen processing and presentation of exogenous peptide antigen via MHC class II
Antigen processing and presentation of peptide antigen via MHC class I
Cellular protein metabolic process
Chaperone-mediated protein folding
Clathrin-dependent endocytosis
Endoplasmic reticulum unfolded protein response
Interleukin-12-mediated signaling pathway
Interleukin-27-mediated signaling pathway
Interleukin-35-mediated signaling pathway
Post-translational protein modification
Protein folding
Protein folding in endoplasmic reticulum
Protein N-linked glycosylation via asparagine
Protein secretion
Synaptic vesicle endocytosis
Viral process
Viral protein processing
Cellular Component
Axon
Dendrite cytoplasm
Dendritic spine
Endoplasmic reticulum
Endoplasmic reticulum lumen
Endoplasmic reticulum membrane
Endoplasmic reticulum quality control compartment
Extracellular exosome
Extracellular matrix
Glutamatergic synapse
Integral component of lumenal side of endoplasmic reticulum membrane
Integral component of postsynaptic membrane
Integral component of presynaptic active zone membrane
Melanosome
Membrane
Mitochondria-associated endoplasmic reticulum membrane
Myelin sheath
Neuronal cell body
Presynapse
Protein complex
Protein-containing complex
Ribosome
Rough endoplasmic reticulum
Smooth endoplasmic reticulum
The reference OMIM entry for this protein is 114217
Calnexin; canx
Cnx
DESCRIPTION
Calnexin is a ubiquitously expressed molecular lectin-like chaperone. Together with calreticulin (CALR; 109091), calnexin promotes folding of glycosylated proteins in the endoplasmic reticulum (ER) (summary by Kraus et al., 2010).CLONING
Calnexin is a 90-kilodalton integral membrane protein of the ER. It exhibits high affinity for binding calcium ions, which was the means by which it was first identified. Calcium ions are known to play a central role in the regulation of cellular metabolism, including signal transduction events and the transport of proteins through the ER. Calnexin has been shown to be associated with several cell surface proteins during translocation through the ER and has been isolated as a complex with other ER proteins involved in calcium ion-dependent retention of proteins. Tjoelker et al. (1994) isolated cDNA clones of the human, mouse, and rat calnexins. Comparisons of the sequences demonstrated a high level of conservation of sequence identity, suggesting that calnexin performs important cellular functions. Schwann cell-derived peripheral myelin protein-22 (PMP22; 601097), when mutated or overexpressed, causes heritable neuropathies with a 'gain-of-function' endoplasmic reticulum (ER) phenotype. PMP22 associates in a specific and transient manner with CANX in wildtype sciatic nerves. In the sciatic nerves of the Trembler (TrJ) mouse carrying the same mutation in the PMP22 gene that causes Charcot-Marie-Tooth disease (CMT
) in the human, Dickson et al. (2002) found prolonged association of mutant PMP22 with CANX. In cultured cells expressing the TrJ mutant PMP22, CANX and PMP22 colocalized in large intracellular structures identified at the electron microscopy level as myelin-like figures, with CANX localization in the structures dependent on PMP22 glucosylation. Similar intracellular myelin-like figures were also present in Schwann cells of sciatic nerves from homozygous TrJ mice. Sequestration of CANX in intracellular myelin-like figures may be relevant to the pathogenesis of autosomal dominantCMT
-related neuropathies.GENE FUNCTION
Using human cell lines, Mueller et al. (2008) identified several components of a protein complex required for retrotranslocation or dislocation of misfolded proteins from the ER lumen to the cytosol for proteasome-dependent degradation. These included SEL1L (602329), HRD1 (SYVN1; 608046), derlin-2 (DERL2; 610304), the ATPase p97 (VCP; 601023), PDI (P4HB; 176790), BIP (HSPA5; 138120), calnexin, AUP1 (602434), UBXD8 (FAF2), UBC6E (UBE2J1; 616175), and OS9 (609677).BIOCHEMICAL FEATURES
Schrag et al. (2001) determined the 3-dimensional structure of the luminal domain of calnexin to 2.9-angstrom resolution. The structure revealed an extended 140-angstrom arm inserted into a beta sandwich structure characteristic of legume lectins. The arm is composed of tandem repeats of 2 proline-rich sequence motifs that interact with one another in a head-to-tail fashion. Identification of the ligand-binding site established calnexin as a monovalent lectin, providing insight into the mechanism by which the calnexin family of chaperones interacts with monoglucosylated glycoproteins.MAPPING
Gray et al. (1993) hybridized a CANX cDNA probe to Southern blots of a panel of 31 EcoRI-digested somatic cell human-mouse hybrid DNAs. The CANX probe segregated concordantly with chromosome 5. In situ hybridization with a tri ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 114217 was added.