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Gene Review

Calr  -  calreticulin

Rattus norvegicus

Synonyms: CABP3, CALBP, CRP55, Calcium-binding protein 3, Calregulin, ...
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Disease relevance of Calr


High impact information on Calr


Chemical compound and disease context of Calr

  • To elucidate whether G(h) mediates norepinephrine-stimulated intracellular signal transductions leading to activation of extracellular signal-regulated kinases (ERKs) and neonatal rat cardiomyocyte hypertrophy, we examined the effects of G(h) on the activation of ERKs and inhibitory effects of CRT on alpha(1)-adrenoceptor/G(h) signaling [2].
  • We report that treatment of rat C6 glioma cells with valproate can also increase the expression of additional endoplasmic reticulum stress proteins, GRP94 and calreticulin [11].

Biological context of Calr


Anatomical context of Calr


Associations of Calr with chemical compounds

  • This enzyme catalyzes the formation of disulfide bonds in CNX and CRT-bound glycoprotein substrates [15].
  • In contrast a calreticulin mutant, which lacked the Ca(2+)-binding domain but included the KDEL sequence, could escape from the ER to a much higher extent [16].
  • Immuno-gold decoration of liver ultrathin cryosections with affinity-purified antibodies against liver calreticulin revealed luminal labelling of vacuolar profiles indistinguishable from calciosomes, the subcellular structures previously identified by the use of anti-calsequestrin antibodies [17].
  • Glucose trimming from newly synthesized glycoproteins regulates their interaction with the calnexin/calreticulin chaperone system [18].
  • Co-overexpression of G(h) and CRT abolished norepinephrine-induced ERKs activation [2].
  • In vitro and in NIH 3T3 cells in culture, the level of arginylated CRT increased with the addition of a Ca2+ chelator to the medium, whereas a decreased arginine incorporation into CRT was found in the presence of Ca2+ [19].

Physical interactions of Calr

  • These results show that calreticulin prevents the binding of vitamin D receptor-retinoid X receptor-beta to the PTH VDRE in gel retardation assays and prevents the transcriptional effect of 1,25-(OH)2D3 on the PTH gene [4].
  • Taken together, our results indicate that PKC interacts in vivo with calreticulin and suggest that they can operate in common signalling pathways [20].

Regulatory relationships of Calr


Other interactions of Calr

  • We further demonstrated that the residues 225-251 at the tip of the CRT P-domain are involved in direct contacts with ERp57 [15].
  • In the present study, we have investigated the interactions of endogenous Tg with calreticulin and with several other ER chaperones [23].
  • Previously, we solved the NMR structure of the central proline-rich P-domain of CRT comprising residues 189-288 [15].
  • Two-dimensional immunoblot analysis of the antigenic proteins revealed that the 56kDa and 55kDa proteins showed 4.2 and 4.0 pI values and were estimated to be protein disulfide isomerase (PDI) and calreticulin, respectively, from NH2-terminal amino acid sequence analysis [24].
  • The results indicate that calreticulin is present in the acrosome of spermatids of rat testes [25].

Analytical, diagnostic and therapeutic context of Calr


  1. Structural homology between the rat calreticulin gene product and the Onchocerca volvulus antigen Ral-1. Murthy, K.K., Banville, D., Srikant, C.B., Carrier, F., Holmes, C., Bell, A., Patel, Y.C. Nucleic Acids Res. (1990) [Pubmed]
  2. Calreticulin inhibits the MEK1,2-ERK1,2 pathway in alpha 1-adrenergic receptor/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes. Lee, K.H., Lee, N., Lim, S., Jung, H., Ko, Y.G., Park, H.Y., Jang, Y., Lee, H., Hwang, K.C. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  3. In vitro reconstitution of calreticulin-substrate interactions. Peterson, J.R., Helenius, A. J. Cell. Sci. (1999) [Pubmed]
  4. Calreticulin inhibits vitamin D's action on the PTH gene in vitro and may prevent vitamin D's effect in vivo in hypocalcemic rats. Sela-Brown, A., Russell, J., Koszewski, N.J., Michalak, M., Naveh-Many, T., Silver, J. Mol. Endocrinol. (1998) [Pubmed]
  5. Effects of prenatal glucocorticoid exposure on cardiac calreticulin and calsequestrin protein expression during early development and in adulthood. Langdown, M.L., Holness, M.J., Sugden, M.C. Biochem. J. (2003) [Pubmed]
  6. Calcium regulates the association between mitochondria and a smooth subdomain of the endoplasmic reticulum. Wang, H.J., Guay, G., Pogan, L., Sauvé, R., Nabi, I.R. J. Cell Biol. (2000) [Pubmed]
  7. NMR structure of the calreticulin P-domain. Ellgaard, L., Riek, R., Herrmann, T., Güntert, P., Braun, D., Helenius, A., Wüthrich, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Recognition of local glycoprotein misfolding by the ER folding sensor UDP-glucose:glycoprotein glucosyltransferase. Ritter, C., Helenius, A. Nat. Struct. Biol. (2000) [Pubmed]
  9. Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation. Crossin, K.L., Tai, M.H., Krushel, L.A., Mauro, V.P., Edelman, G.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  10. Competition for access to the rat major histocompatibility complex class I peptide-loading complex reveals optimization of peptide cargo in the absence of transporter associated with antigen processing (TAP) association. Ford, S., Antoniou, A., Butcher, G.W., Powis, S.J. J. Biol. Chem. (2004) [Pubmed]
  11. Increased expression of endoplasmic reticulum stress proteins following chronic valproate treatment of rat C6 glioma cells. Bown, C.D., Wang, J.F., Young, L.T. Neuropharmacology (2000) [Pubmed]
  12. Overexpression of calreticulin modulates protein kinase B/Akt signaling to promote apoptosis during cardiac differentiation of cardiomyoblast H9c2 cells. Kageyama, K., Ihara, Y., Goto, S., Urata, Y., Toda, G., Yano, K., Kondo, T. J. Biol. Chem. (2002) [Pubmed]
  13. An endoplasmic reticulum protein, calreticulin, is transported into the acrosome of rat sperm. Nakamura, M., Moriya, M., Baba, T., Michikawa, Y., Yamanobe, T., Arai, K., Okinaga, S., Kobayashi, T. Exp. Cell Res. (1993) [Pubmed]
  14. Intracellular Ca2+ stores of T lymphocytes: changes induced by in vitro and in vivo activation. Clementi, E., Martino, G., Grimaldi, L.M., Brambilla, E., Meldolesi, J. Eur. J. Immunol. (1994) [Pubmed]
  15. NMR structures of 36 and 73-residue fragments of the calreticulin P-domain. Ellgaard, L., Bettendorff, P., Braun, D., Herrmann, T., Fiorito, F., Jelesarov, I., Güntert, P., Helenius, A., Wüthrich, K. J. Mol. Biol. (2002) [Pubmed]
  16. Retention and retrieval: both mechanisms cooperate to maintain calreticulin in the endoplasmic reticulum. Sönnichsen, B., Füllekrug, J., Nguyen Van, P., Diekmann, W., Robinson, D.G., Mieskes, G. J. Cell. Sci. (1994) [Pubmed]
  17. Calreticulin is a candidate for a calsequestrin-like function in Ca2(+)-storage compartments (calciosomes) of liver and brain. Treves, S., De Mattei, M., Landfredi, M., Villa, A., Green, N.M., MacLennan, D.H., Meldolesi, J., Pozzan, T. Biochem. J. (1990) [Pubmed]
  18. Quaternary and domain structure of glycoprotein processing glucosidase II. Trombetta, E.S., Fleming, K.G., Helenius, A. Biochemistry (2001) [Pubmed]
  19. Post-translational arginylation of calreticulin: a new isospecies of calreticulin component of stress granules. Decca, M.B., Carpio, M.A., Bosc, C., Galiano, M.R., Job, D., Andrieux, A., Hallak, M.E. J. Biol. Chem. (2007) [Pubmed]
  20. Characterization of calreticulin as a protein interacting with protein kinase C. Rendón-Huerta, E., Mendoza-Hernández, G., Robles-Flores, M. Biochem. J. (1999) [Pubmed]
  21. Calreticulin inhibits glucocorticoid- but not cAMP-sensitive expression of tyrosine aminotransferase gene in cultured McA-RH7777 hepatocytes. Burns, K., Opas, M., Michalak, M. Mol. Cell. Biochem. (1997) [Pubmed]
  22. Heat shock-regulated expression of calreticulin in retinal pigment epithelium. Szewczenko-Pawlikowski, M., Dziak, E., McLaren, M.J., Michalak, M., Opas, M. Mol. Cell. Biochem. (1997) [Pubmed]
  23. Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. Di Jeso, B., Ulianich, L., Pacifico, F., Leonardi, A., Vito, P., Consiglio, E., Formisano, S., Arvan, P. Biochem. J. (2003) [Pubmed]
  24. Identification of protein disulfide isomerase and calreticulin as autoimmune antigens in LEC strain of rats. Yokoi, T., Nagayama, S., Kajiwara, R., Kawaguchi, Y., Horiuchi, R., Kamataki, T. Biochim. Biophys. Acta (1993) [Pubmed]
  25. Calreticulin is present in the acrosome of spermatids of rat testis. Nakamura, M., Michikawa, Y., Baba, T., Okinaga, S., Arai, K. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  26. Calreticulin--an endoplasmic reticulum protein with calcium-binding activity is also found in the extracellular matrix. Somogyi, E., Petersson, U., Hultenby, K., Wendel, M. Matrix Biol. (2003) [Pubmed]
  27. Calreticulin-melatonin. An unexpected relationship. Macías, M., Escames, G., Leon, J., Coto, A., Sbihi, Y., Osuna, A., Acuña-Castroviejo, D. Eur. J. Biochem. (2003) [Pubmed]
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