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Gene Review

CALCR  -  calcitonin receptor

Homo sapiens

Synonyms: CRT, CT-R, CTR, CTR1, Calcitonin receptor
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Disease relevance of CALCR


Psychiatry related information on CALCR

  • These results suggest that N-PCT can function as an endogenous ligand for the CT receptor and may act as a catabolic signaling molecule in the central regulation of feeding behavior and energy homeostasis [5].
  • The performance of 56 homosexual men infected with human immunodeficiency virus (HIV) was compared to that of 23 HIV antibody-seronegative controls on simple (SRT) and choice (CRT) reaction time tasks [6].
  • For the patients with Huntington's disease, this CRT/SRT difference was not significant [7].
  • There was no instance of ventricular proarrhythmia associated with atrial shock therapies, undersensing of ventricular arrhythmias, or interruption of CRT therapy associated with the combined device [8].
  • In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory) [9].

High impact information on CALCR

  • Mutants in CTR1 exhibit a constitutive ethylene-response phenotype [10].
  • Both the ethylene receptors and CTR1 are negative regulators of ethylene responses [10].
  • Although the calcitonin receptor does not require RAMP to bind and respond to calcitonin, it can associate with the RAMPs, resulting in a series of receptors that typically have high affinity for amylin and varied affinity for CGRP [11].
  • Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family [12].
  • Thr-4 residues of the CTR repeats are functionally important phosphorylation sites [13].

Chemical compound and disease context of CALCR


Biological context of CALCR


Anatomical context of CALCR


Associations of CALCR with chemical compounds

  • The expressed hCTR was coupled to adenylate cyclase [2].
  • Attenuation of CT-induced CTR down-regulation by the competitive cAMP antagonist, RpcAMP, and high concentrations of H-7, but not by protein kinase C-specific inhibitors (sphingosine, staurosporine, and a lower concentration of H-7), suggested that the PKA pathway is primarily involved in homologous regulation of the CTR [20].
  • Biological activity of immunoreactive human and mouse IAPP components derived from pancreatic extracts was assessed by calcitonin receptor-mediated stimulation of cyclic AMP accumulation in T47D human breast carcinoma cells [22].
  • Calcitonin receptor mRNA expression in TT cells: effect of dexamethasone [23].
  • Two alleles of the calcitonin receptor gene ( CTR ) exist: a base mutation T-->C in the third intracellular C-terminal domain changes a proline (CCG) at position 447 to a leucine (CTG) [24].
  • Deletion and/or alanine replacement of the region of the calcitonin receptor between residues 150 and 153 resulted in marked reduction in cAMP responses to these compounds, with some compound-specific differences observed, supporting a critical role for this region [25].

Physical interactions of CALCR

  • CHO-P cells provide an environment conducive to a low, but significant, level of amylin binding with either hCTR isoform alone, unlike in COS-7, where RAMP coexpression is imperative for amylin binding [26].
  • The distinct functional characteristics of GC-2 and GC-10, which differ in structure only in the first intracellular domain, indicate that the first intracellular domain of the CTR plays a previously unidentified role in modulating ligand binding and signal transduction via the G protein/adenylate cyclase system [19].
  • In a two-hybrid screening, we found that the actin-binding protein filamin interacted with the C-terminal tail of the CTR [27].
  • These studies suggest that CGRP initially interacts with the calcitonin receptor to produce a calcitonin-like effect, which is followed by hypercalcaemia presumably by antagonising the action of endogenous circulating calcitonin [28].
  • Thus, membrane-bound TcCRT interacts with the collagenous portion Clq, and this Clq is recognized by the CD91-bound host cell CRT, thus facilitating parasite internalization [29].

Regulatory relationships of CALCR


Other interactions of CALCR


Analytical, diagnostic and therapeutic context of CALCR


  1. The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion associated with the Williams syndrome. Pérez Jurado, L.A., Li, X., Francke, U. Cytogenet. Cell Genet. (1995) [Pubmed]
  2. Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line. Gorn, A.H., Lin, H.Y., Yamin, M., Auron, P.E., Flannery, M.R., Tapp, D.R., Manning, C.A., Lodish, H.F., Krane, S.M., Goldring, S.R. J. Clin. Invest. (1992) [Pubmed]
  3. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATc1, and calcitonin receptor-positive but require receptor activator of NFkappaB ligand for bone resorption. Kim, M.S., Day, C.J., Selinger, C.I., Magno, C.L., Stephens, S.R., Morrison, N.A. J. Biol. Chem. (2006) [Pubmed]
  4. Calcitonin receptor gene polymorphism in japanese women: correlation with body mass and bone mineral density. Nakamura, M., Morimoto, S., Zhang, Z., Utsunomiya, H., Inagami, T., Ogihara, T., Kakudo, K. Calcif. Tissue Int. (2001) [Pubmed]
  5. N-procalcitonin: central effects on feeding and energy homeostasis in rats. Tavares, E., Maldonado, R., Miñano, F.J. Endocrinology (2007) [Pubmed]
  6. Simple and choice reaction time in patients with human immunodeficiency virus infection. Perdices, M., Cooper, D.A. Ann. Neurol. (1989) [Pubmed]
  7. A comparative study of simple and choice reaction time in Parkinson's, Huntington's and cerebellar disease. Jahanshahi, M., Brown, R.G., Marsden, C.D. J. Neurol. Neurosurg. Psychiatr. (1993) [Pubmed]
  8. Results of the multicenter RENEWAL 3 AVT clinical study of cardiac resynchronization defibrillator therapy in patients with paroxysmal atrial fibrillation. Saxon, L.A., Greenfield, R.A., Crandall, B.G., Nydegger, C.C., Orlov, M., VAN Genderen, R. J. Cardiovasc. Electrophysiol. (2006) [Pubmed]
  9. Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist. Patat, A., Molinier, P., Hergueta, T., Brohier, S., Zieleniuk, I., Danjou, P., Warot, D., Puech, A. International clinical psychopharmacology. (1994) [Pubmed]
  10. Ethylene: a gaseous signal molecule in plants. Bleecker, A.B., Kende, H. Annu. Rev. Cell Dev. Biol. (2000) [Pubmed]
  11. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Poyner, D.R., Sexton, P.M., Marshall, I., Smith, D.M., Quirion, R., Born, W., Muff, R., Fischer, J.A., Foord, S.M. Pharmacol. Rev. (2002) [Pubmed]
  12. A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Jüppner, H., Abou-Samra, A.B., Freeman, M., Kong, X.F., Schipani, E., Richards, J., Kolakowski, L.F., Hock, J., Potts, J.T., Kronenberg, H.M. Science (1991) [Pubmed]
  13. P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation. Yamada, T., Yamaguchi, Y., Inukai, N., Okamoto, S., Mura, T., Handa, H. Mol. Cell (2006) [Pubmed]
  14. Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation. Mulhern, R.K., Wasserman, A.L., Fairclough, D., Ochs, J. J. Clin. Oncol. (1988) [Pubmed]
  15. Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells. Holzer, A.K., Katano, K., Klomp, L.W., Howell, S.B. Clin. Cancer Res. (2004) [Pubmed]
  16. Breast cancer cell response to calcitonin: modulation by growth-regulating agents. Lacroix, M., Siwek, B., Body, J.J. Eur. J. Pharmacol. (1998) [Pubmed]
  17. Calcitonin receptor gene polymorphism: a possible genetic marker for patients with calcium oxalate stones. Chen, W.C., Wu, H.C., Lu, H.F., Chen, H.Y., Tsai, F.J. Eur. Urol. (2001) [Pubmed]
  18. Intermediate dose methotrexate in childhood acute lymphoblastic leukemia resulting in decreased incidence of testicular relapse. Brecher, M.L., Weinberg, V., Boyett, J.M., Sinks, L.F., Jones, B., Glicksman, A., Holland, J.F., Freeman, A.I. Cancer (1986) [Pubmed]
  19. Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction. Gorn, A.H., Rudolph, S.M., Flannery, M.R., Morton, C.C., Weremowicz, S., Wang, T.Z., Krane, S.M., Goldring, S.R. J. Clin. Invest. (1995) [Pubmed]
  20. Physiological levels of calcitonin regulate the mouse osteoclast calcitonin receptor by a protein kinase Alpha-mediated mechanism. Wada, S., Udagawa, N., Nagata, N., Martin, T.J., Findlay, D.M. Endocrinology (1996) [Pubmed]
  21. A novel calcitonin receptor gene in human osteoclasts from normal bone marrow. Nishikawa, T., Ishikawa, H., Yamamoto, S., Koshihara, Y. FEBS Lett. (1999) [Pubmed]
  22. Biologically active human islet amyloid polypeptide/amylin in transgenic mice. van Hulst, K.L., Born, W., Muff, R., Oosterwijk, C., Blankenstein, M.A., Lips, C.J., Fischer, J.A., Höppener, J.W. Eur. J. Endocrinol. (1997) [Pubmed]
  23. Calcitonin receptor mRNA expression in TT cells: effect of dexamethasone. Frendo, J.L., Delage-Mourroux, R., Cohen, R., Pichaud, F., Pidoux, E., Guliana, J.M., Jullienne, A. Mol. Cell. Endocrinol. (1998) [Pubmed]
  24. Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Taboulet, J., Frenkian, M., Frendo, J.L., Feingold, N., Jullienne, A., de Vernejoul, M.C. Hum. Mol. Genet. (1998) [Pubmed]
  25. Juxtamembranous region of the amino terminus of the family B G protein-coupled calcitonin receptor plays a critical role in small-molecule agonist action. Dong, M., Cox, R.F., Miller, L.J. J. Biol. Chem. (2009) [Pubmed]
  26. Amylin receptor phenotypes derived from human calcitonin receptor/RAMP coexpression exhibit pharmacological differences dependent on receptor isoform and host cell environment. Tilakaratne, N., Christopoulos, G., Zumpe, E.T., Foord, S.M., Sexton, P.M. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  27. Binding of filamin to the C-terminal tail of the calcitonin receptor controls recycling. Seck, T., Baron, R., Horne, W.C. J. Biol. Chem. (2003) [Pubmed]
  28. A dual effect of calcitonin gene-related peptide on plasma calcium levels in the chick. Bevis, P.J., Zaidi, M., MacIntyre, I. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  29. F(ab')2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement. Aguilar, L., Ramírez, G., Valck, C., Molina, M.C., Rojas, A., Schwaeble, W., Ferreira, V., Ferreira, A. Biol. Res. (2005) [Pubmed]
  30. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Christopoulos, G., Perry, K.J., Morfis, M., Tilakaratne, N., Gao, Y., Fraser, N.J., Main, M.J., Foord, S.M., Sexton, P.M. Mol. Pharmacol. (1999) [Pubmed]
  31. Islet amyloid polypeptide stimulates cyclic AMP accumulation via the porcine calcitonin receptor. Christmanson, L., Westermark, P., Betsholtz, C. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  32. Calcitonin receptor mRNA expression in the human prostate. Wu, G., Burzon, D.T., di Sant'Agnese, P.A., Schoen, S., Deftos, L.J., Gershagen, S., Cockett, A.T. Urology (1996) [Pubmed]
  33. Calcitonin is a prostate epithelium-derived growth stimulatory peptide. Chien, J., Ren, Y., Qing Wang, Y., Bordelon, W., Thompson, E., Davis, R., Rayford, W., Shah, G. Mol. Cell. Endocrinol. (2001) [Pubmed]
  34. Phospholipase D- and protein kinase C isoenzyme-dependent signal transduction pathways activated by the calcitonin receptor. Naro, F., Perez, M., Migliaccio, S., Galson, D.L., Orcel, P., Teti, A., Goldring, S.R. Endocrinology (1998) [Pubmed]
  35. A critical role for the short intracellular C terminus in receptor activity-modifying protein function. Udawela, M., Christopoulos, G., Morfis, M., Christopoulos, A., Ye, S., Tilakaratne, N., Sexton, P.M. Mol. Pharmacol. (2006) [Pubmed]
  36. Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins. Kuwasako, K., Kitamura, K., Nagoshi, Y., Eto, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  37. Receptor pharmacology. Young, A. Adv. Pharmacol. (2005) [Pubmed]
  38. Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene. Albrandt, K., Brady, E.M., Moore, C.X., Mull, E., Sierzega, M.E., Beaumont, K. Endocrinology (1995) [Pubmed]
  39. Postmenopausal serum androstenedione levels are associated with the calcitonin receptor gene polymorphism T1377c. A pilot study. Zofková, I., Zajicková, K., Hill, M. J. Endocrinol. Invest. (2004) [Pubmed]
  40. Does polymorphism C1377T of the calcitonin receptor gene determine bone mineral density in postmenopausal women? Zofková, I., Zajícková, K., Hill, M., Krepelová, A. Exp. Clin. Endocrinol. Diabetes (2003) [Pubmed]
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