Calnexin
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
| Calnexin
| |||||||||||||||||||||||||||||||||||||||
| Image:Calnexin 1JHN.png | |||||||||||||||||||||||||||||||||||||||
| Lumenal domain of calnexin from PDB 1JHN. | |||||||||||||||||||||||||||||||||||||||
| Available structures: For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.
HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
Note that theoretical models are no longer accepted in the PDB. 22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file. The current breakdown of holdings is updated weekly. File formatThrough the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.
This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects; The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs. If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction). Various funding agencies and scientific journals now require scientists to submit their structure data to PDB. Viewing the dataThe structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software. ReferencesPrinted
Online
Other external links
Links to enzyme database data
Molecular graphic visualisation tools
| |||||||||||||||||||||||||||||||||||||||
| Identifiers | |||||||||||||||||||||||||||||||||||||||
| Symbol(s) | CANX; CNX; FLJ26570; IP90; P90 | ||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 114217 MGI: 88261 Homologene: 1324 | ||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||
| RNA expression pattern | |||||||||||||||||||||||||||||||||||||||
| Image:PBB GE CANX 208852 s at tn.png | |||||||||||||||||||||||||||||||||||||||
| Orthologs | |||||||||||||||||||||||||||||||||||||||
| Human | Mouse | ||||||||||||||||||||||||||||||||||||||
| Entrez | 821 | 12330 | |||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000127022 | ENSMUSG00000020368 | |||||||||||||||||||||||||||||||||||||
| Uniprot | P27824 | Q3TXE5 | |||||||||||||||||||||||||||||||||||||
| Refseq | NM_001024649 (mRNA) NP_001019820 (protein) | NM_007597 (mRNA) NP_031623 (protein) | |||||||||||||||||||||||||||||||||||||
| Location | Chr 5: 179.06 - 179.09 Mb | Chr 11: 50.14 - 50.17 Mb | |||||||||||||||||||||||||||||||||||||
| Pubmed search | [5] | [6] | |||||||||||||||||||||||||||||||||||||
Calnexin (CNX) is a 90kDa integral protein 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 endoplasmic reticulum.
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.
ATP and Ca++ 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.
External links
Further reading
- Kleizen B, Braakman I (2005). "Protein folding and quality control in the endoplasmic reticulum.". Curr. Opin. Cell Biol. 16 (4): 343-9. doi:10.1016/j.ceb.2004.06.012. PMID 15261665.
- Rasmussen HH, van Damme J, Puype M, et al. (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.". Electrophoresis 13 (12): 960-9. PMID 1286667.
- Galvin K, Krishna S, Ponchel F, et al. (1992). "The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene.". Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8452-6. PMID 1326756.
- Pind S, Riordan JR, Williams DB (1994). "Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator.". J. Biol. Chem. 269 (17): 12784-8. PMID 7513695.
- Honoré B, Rasmussen HH, Celis A, et al. (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. PMID 8055875.
- Tjoelker LW, Seyfried CE, Eddy RL, et al. (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. PMID 8136357.
- Lenter M, Vestweber D (1994). "The integrin chains beta 1 and alpha 6 associate with the chaperone calnexin prior to integrin assembly.". J. Biol. Chem. 269 (16): 12263-8. PMID 8163531.
- Rajagopalan S, Xu Y, Brenner MB (1994). "Retention of unassembled components of integral membrane proteins by calnexin.". Science 263 (5145): 387-90. PMID 8278814.
- David V, Hochstenbach F, Rajagopalan S, Brenner MB (1993). "Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin).". J. Biol. Chem. 268 (13): 9585-92. PMID 8486646.
- Bellovino D, Morimoto T, Tosetti F, Gaetani S (1996). "Retinol binding protein and transthyretin are secreted as a complex formed in the endoplasmic reticulum in HepG2 human hepatocarcinoma cells.". Exp. Cell Res. 222 (1): 77-83. doi:10.1006/excr.1996.0010. PMID 8549676.
- Otteken A, Moss B (1996). "Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin.". J. Biol. Chem. 271 (1): 97-103. PMID 8550632.
- Devergne O, Hummel M, Koeppen H, et al. (1996). "A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes.". J. Virol. 70 (2): 1143-53. PMID 8551575.
- Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107-13. doi:10.1006/abio.1996.0138. PMID 8619474.
- van Leeuwen JE, Kearse KP (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.". J. Biol. Chem. 271 (16): 9660-5. PMID 8621641.
- Oliver JD, Hresko RC, Mueckler M, High S (1996). "The glut 1 glucose transporter interacts with calnexin and calreticulin.". J. Biol. Chem. 271 (23): 13691-6. PMID 8662691.
- Li Y, Bergeron JJ, Luo L, et al. (1996). "Effects of inefficient cleavage of the signal sequence of HIV-1 gp 120 on its association with calnexin, folding, and intracellular transport.". Proc. Natl. Acad. Sci. U.S.A. 93 (18): 9606-11. PMID 8790377.
- Trombetta ES, Simons JF, Helenius A (1996). "Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit.". J. Biol. Chem. 271 (44): 27509-16. PMID 8910335.
- Tatu U, Helenius A (1997). "Interactions between newly synthesized glycoproteins, calnexin and a network of resident chaperones in the endoplasmic reticulum.". J. Cell Biol. 136 (3): 555-65. PMID 9024687.
- Wiest DL, Bhandoola A, Punt J, et al. (1997). "Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of "ER-resident" molecular chaperones.". Proc. Natl. Acad. Sci. U.S.A. 94 (5): 1884-9. PMID 9050874.
- Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353-8. PMID 9110174.
Carrier protein: calcium-binding proteins | |
|---|---|
| Intracellular calcium-sensing proteins | Calmodulin - Calnexin - Calreticulin - Gelsolin - neuronal (Hippocalcin, Neurocalcin, Recoverin) |
| Other | Annexin (A1, A2, A5) - Vitamin D-dependent calcium-binding protein/Calbindin - Calexcitin - Calsequestrin - Osteocalcin - Matrix gla protein - Osteonectin - S-100 - Synaptotagmin - Troponin C |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
