Calreticulin

Calreticulin
PDB rendering based on 1hhn.
Available structures: 1hhn, 1k91, 1k9c
Identifiers
Symbol(s)	CALR; FLJ26680; RO; SSA; cC1qR
External IDs	OMIM: 109091 MGI: 88252 Homologene: 37911
Gene Ontology Molecular Function: • DNA binding • calcium ion binding • sugar binding • zinc ion binding • unfolded protein binding Cellular Component: • extracellular space • endoplasmic reticulum • endoplasmic reticulum lumen • cytosol • external side of plasma membrane Biological Process: • regulation of transcription, DNA-dependent • protein folding • protein export from nucleus • cellular calcium ion homeostasis • cortical actin cytoskeleton organization and biogenesis • regulation of meiosis • regulation of apoptosis
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	811	12317
Ensembl	ENSG00000179218	ENSMUSG00000003814
Uniprot	P27797	Q3TVD2
Refseq	NM_004343 (mRNA) NP_004334 (protein)	NM_007591 (mRNA) NP_031617 (protein)
Location	Chr 19: 12.91 - 12.92 Mb	Chr 8: 87.73 - 87.74 Mb
Pubmed search	[1]	[2]

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]

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 of 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.

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.

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]

References

Further reading

External links

• MeSH Calreticulin