Synonyms
Historical Background
Calreticulin was discovered in the early 1970s as a high affinity calcium-binding protein (HACBP) of the sarcoplasmic reticulum (Ostwald and MacLennan 1974). Later, based on N-terminal amino acid sequence analysis and molecular cloning of cDNA encoding calreticulin, it was realized that the protein was identical to calregulin, CRP55, CaBP3, ERp60, and calsequestrin-like protein (Michalak et al. 2009). The name “calreticulin” is now universally accepted to reflect the protein’s Ca2+binding capacity and localization in the sarcoplasmic/endoplasmic reticulum (ER). Calreticulin is a ubiquitous protein that is present in all eukaryotic cells except for erythrocytes, as these cells lack ER. There is reduced abundance of calreticulin in differentiated tissues (heart and brain), while highly...
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References
Chao MP, Jaiswal S, Weissman-Tsukamoto R, Alizadeh AA, Gentles AJ, Volkmer J, Weiskopf K, Willingham SB, Raveh T, Park CY, Majeti R, Weissman IL. Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med. 2010;2(63):63ra94.
Chouquet A, Paidassi H, Ling WL, Frachet P, Houen G, Arlaud GJ, Gaboriaud C. X-ray structure of the human calreticulin globular domain reveals a peptide-binding area and suggests a multi-molecular mechanism. PLoS One. 2011;6(3):e17886.
Coe H, Jung J, Groenendyk J, Prins D, Michalak M. ERp57 modulates STAT3 signaling from the lumen of the endoplasmic reticulum. J Biol Chem. 2010;285(9):6725–38.
Eggleton P, Michalak M. Calreticulin for better or for worse, in sickness and in health, until death do us part. Cell Calcium. 2013;54(2):126–31.
Eggleton P, Bremer E, Dudek E, Michalak M. Calreticulin, a therapeutic target? Expert Opin Ther Targets. 2016;20(9):1137–47.
Ellgaard L, Riek R, Herrmann T, Guntert P, Braun D, Helenius A, Wuthrich K. NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA. 2001;98(6):3133–8.
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell. 2005;123(2):321–34.
Goicoechea S, Pallero MA, Eggleton P, Michalak M, Murphy-Ullrich JE. The anti-adhesive activity of thrombospondin is mediated by the N-terminal domain of cell surface calreticulin. J Biol Chem. 2002;277(40):37219–28.
Gold LI, Rahman M, Blechman KM, Greives MR, Churgin S, Michaels J, Callaghan MJ, Cardwell NL, Pollins AC, Michalak M, Siebert JW, Levine JP, Gurtner GC, Nanney LB, Galiano RD, Cadacio CL. Overview of the role for calreticulin in the enhancement of wound healing through multiple biological effects. J Investig Dermatol Symp Proc. 2006;11(1):57–65.
Gold LI, Eggleton P, Sweetwyne MT, Van Duyn LB, Greives MR, Naylor SM, Michalak M, Murphy-Ullrich JE. Calreticulin: non-endoplasmic reticulum functions in physiology and disease. FASEB J. 2010;24(3):665–83.
Groenendyk J, Lee D, Jung J, Dyck JR, Lopaschuk GD, Agellon LB, Michalak M. Inhibition of the unfolded protein response mechanism prevents cardiac fibrosis. PLoS One. 2016;11(7):e0159682.
Ignacio Arias J, Sepulveda C, Bravo P, Hamilton-West C, Maldonado I, Ferreira A. Comparative effect of human and Trypanosoma cruzi calreticulin in wound healing. J Tissue Eng Regen Med. 2015;9(1):41–54.
Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity. 2013;38(2):209–23.
Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant’Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schonegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.
Lin Q, Cao Y, Gao J. Serum calreticulin is a negative biomarker in patients with Alzheimer’s disease. Int J Mol Sci. 2014;15(12):21740–53.
Ling S, Cline EN, Haug TS, Fox DA, Holoshitz J. Citrullinated calreticulin potentiates rheumatoid arthritis shared epitope signaling. Arthritis Rheum. 2013;65(3):618–26.
Lopez Sambrooks C, Carpio MA, Hallak ME. Arginylated calreticulin at plasma membrane increases susceptibility of cells to apoptosis. J Biol Chem. 2012;287(26):22043–54.
Lu YC, Weng WC, Lee H. Functional roles of calreticulin in cancer biology. Biomed Res Int. 2015;2015:526524.
Mesaeli N, Nakamura K, Zvaritch E, Dickie P, Dziak E, Krause KH, Opas M, MacLennan DH, Michalak M. Calreticulin is essential for cardiac development. J Cell Biol. 1999;144(5):857–68.
Michalak M, Groenendyk J, Szabo E, Gold LI, Opas M. Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum. Biochem J. 2009;417(3):651–66.
Nakamura K, Zuppini A, Arnaudeau S, Lynch J, Ahsan I, Krause R, Papp S, De Smedt H, Parys JB, Müller-Esterl W, Lew DP, Krause K-H, Demaurex N, Opas M, Michalak M. Functional specialization of calreticulin domains. J Cell Biol. 2001;154:961–72.
Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O’Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M, Bowen D, Huntly BJ, Harrison CN, Cross NC, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.
Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13(1):54–61.
Ostwald TJ, MacLennan DH. Isolation of a high affinity calcium-binding protein from sarcoplasmic reticulum. J Biol Chem. 1974;249:974–9.
Park BJ, Lee DG, Yu JR, Jung SK, Choi K, Lee J, Lee J, Kim YS, Lee JI, Kwon JY, Lee J, Singson A, Song WK, Eom SH, Park CS, Kim DH, Bandyopadhyay J, Ahnn J. Calreticulin, a calcium-binding molecular chaperone, is required for stress response and fertility in Caenorhabditis elegans. Mol Biol Cell. 2001;12(9):2835–45.
Peaper DR, Cresswell P. Regulation of MHC class I assembly and peptide binding. Annu Rev Cell Dev Biol. 2008;24:343–68.
Qiu Y, Michalak M. Transcriptional control of the calreticulin gene in health and disease. Int J Biochem Cell Biol. 2009;41(3):531–8.
Rubinstein AL, Lee D, Luo R, Henion PD, Halpern ME. Genes dependent on zebrafish cyclops function identified by AFLP differential gene expression screen. Genesis. 2000;26:86–97.
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Dudek, E., Michalak, M. (2018). Calreticulin. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101570
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101570
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