Calreticulin
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Calreticulin is a multifunctional protein that binds Ca2+ ions (a second messenger molecule in signal transduction), rendering it inactive. The Ca2+ is bound with low affinity, but high capacity, and can be released on a signal (see inositol triphosphate). Calreticulin is located in storage compartments associated with the endoplasmic reticulum.
Calreticulin is also known as calregulin, CRP55, CaBP3 and calsequestrin-like protein. The term "Mobilferrin"[1] is considered to be the same as calreticulin by some sources.[2]
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[edit] Functions
Calreticulin binds to misfolded proteins and prevents them from being exported from the Endoplasmic reticulum to the Golgi apparatus.
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. In normal cellular function, trimming of glucose residues off the core oligosaccharide added during N-linked glycosylation is a part of protein processing. If "overseer" enzymes note that residues are misfolded, proteins within the RER will re-add glucose resides so that other Calreticulin/Calnexin can bind to these proteins and prevent them from proceeding to the Golgi. This leads these aberrantly folded proteins down a path whereby they are targeted for degradation.
[edit] Transcription regulation
Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin binds to the synthetic peptide KLGFFKR, which is almost identical to an amino acid sequence in the DNA-binding domain of the superfamily of nuclear receptors. The amino terminus of calreticulin interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. Calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element and can inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Thus, calreticulin can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors.
[edit] Disease
Calreticulin binds to antibodies in certain sera of systemic lupus and Sjogren patients which contain anti-Ro/SSA antibodies. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen, but this was later disproven. Increased autoantibody titer against human calreticulin is found in infants with complete congenital heart block of both the IgG and IgM classes.[3]
[edit] References
- ^ MeSH Mobilferrin
- ^ Beutler E, West C, Gelbart T (1997). "HLA-H and associated proteins in patients with hemochromatosis". Mol. Med. 3 (6): 397-402. PMID 9234244.
- ^ Entrez Gene: CALR calreticulin.
[edit] Further reading
- Coppolino MG, Dedhar S (1998). "Calreticulin.". Int. J. Biochem. Cell Biol. 30 (5): 553-8. PMID 9693955.
[edit] External links
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