Calreticulin

from Wikipedia, the free encyclopedia
Calreticulin
Properties of human protein
Mass / length primary structure 400 amino acids
Secondary to quaternary structure Monomer
Cofactor Ca 2+ , Zn 2+
Identifier
Gene name CALR
External IDs
Occurrence
Parent taxon Eukaryotes
Orthologue
human House mouse
Entrez 811 12317
Ensemble ENSG00000179218 ENSMUSG00000003814
UniProt P27797 P14211
Refseq (mRNA) NM_004343 NM_007591
Refseq (protein) NP_004334 NP_031617
Gene locus Chr 19: 12.94 - 12.94 Mb Chr 8: 84.84 - 84.85 Mb
PubMed search 811 12317

Calreticulin (CALR) is a protein that is part of a protein complex in the lumen of the endoplasmic reticulum (ER) of eukaryotes . Calreticulin works together with calnexin as a chaperone during the folding of glycoproteins in the endoplasmic reticulum . To do this, it binds to glycoproteins with a terminal glucose residue , which marks the protein as not yet correctly folded, and thus protects it from environmental influences so that it can fold properly.

In addition to the quality control of the proper glycoprotein folding and securing the calcium - homeostasis in the ER CALR has numerous functions outside the ER, so in the cytoplasm, on the cell surface and in the extracellular matrix and affect cell proliferation , apoptosis , phagocytosis and immune response . CALR can also activate the JAK-STAT signaling pathway in hematopoietic cells.

It also binds a cofactor (ERp57) that promotes the formation of disulfide bridges.

The CALR peptide consists of three main structural domains. At the N -terminus there is a lectin- binding domain with interposed proline -rich domains, and at the C -terminus there is an acidic domain with numerous calcium binding sites and a KDEL sequence, which is typical for ER-permanent peptides and their return transfer the Golgi apparatus into the ER.

mutation

In 2013, mutations in the CALR gene were described in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). These CALR mutations were found in around 70 to 84% of the ET and PMF cases that did not have a JAK2 mutation . The pathogenetic role of the CALR mutations in the development of these myeloproliferative neoplasms is not yet fully understood. The detection of CALR mutations is, however, an aid in the diagnosis of myeloproliferative neoplasias . It is possible using molecular diagnostic methods and antibodies .

All mutations found so far are located in the last coding exon of CALR and, through gene insertions or deletions, lead to a shift in the reading frame ( frameshifts ) during translation and thus to a modified carboxy / C terminus of the calreticulin protein. This C-terminal protein domain is normally highly acidic and contains numerous calcium binding sites as well as a recognition sequence (KDEL) typical of proteins that remain in the endoplasmic reticulum. The mutated C-terminal domain, on the other hand, is basic and lacks the calcium binding sites and the KDEL sequence.

Individual evidence

  1. ↑ Homologues at OMA
  2. ↑ Better diagnostics for MPN diseases. In : wirtschaft-news.com. September 23, 2015, accessed May 2, 2018 .
  3. ↑ Data sheet CAL2 antibodies. In: website dianova. Retrieved May 2, 2018 .
  4. ↑ J. Nangalia, CE Massie, EJ Baxter, Nice FL, G. Gundem, DC Wedge, E. Avezov, J. Li, K. Kollmann, DG Kent, A. Aziz, AL Godfrey, J. Hinton, I. Martincorena , P. Van Loo, AV Jones, P. Guglielmelli, P. Tarpey, HP Harding, JD Fitzpatrick, CT Goudie, CA Ortmann, SJ Loughran, K. Raine, DR Jones, AP Butler, JW Teague, S. O'Meara , S. McLaren, M. Bianchi, Y. Silber, D. Dimitropoulou, D. Bloxham, L. Mudie, M. Maddison, B. Robinson, C. Keohane, C. Maclean, K. Hill, K. Orchard, S. Tauro, M.-Q. Du, M. Greaves, D. Bowen, BJP Huntly, CN Harrison, NCP Cross, D. Ron, AM Vannucchi, E. Papaemmanuil, PJ Campbell, AR Green: Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2 New England Journal of Medicine 2013, Volume 369, Issue 25 of December 19, 2013, pp. 2391-2405; DOI: 10.1056 / NEJMoa1312542