Contents:
- Quaternary Structure
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Immuno Process Associations
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Biologically Significant Variants
- General Comments
- References
- Contributors
- How to cite this page
| Quaternary Structure: Complexes |
| AMY1 receptor |
| AMY2 receptor |
| AMY3 receptor |
Gene and Protein Information  |
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| class B G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 474 | 7q21.3 | CALCR | calcitonin receptor | 31 |
| Mouse | 7 | 533 | 6 1.81 cM | Calcr | calcitonin receptor | 19,42 |
| Rat | 7 | 516 | 4q13 | Calcr | calcitonin receptor | |
| Previous and Unofficial Names |
| CTRI1- | CTR2 | C1A/C1B | CT-R | calcitonin receptor | CTR |
| Database Links |
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| Specialist databases | |
| GPCRdb | calcr_human (Hs), calcr_mouse (Mm), calcr_rat (Rn) |
| Other databases | |
| Alphafold | P30988 (Hs), Q60755 (Mm), P32214 (Rn) |
| CATH/Gene3D | 4.10.1240.10 |
| ChEMBL Target | CHEMBL1832 (Hs), CHEMBL2204 (Rn) |
| DrugBank Target | P30988 (Hs) |
| Ensembl Gene | ENSG00000004948 (Hs), ENSMUSG00000023964 (Mm), ENSRNOG00000010053 (Rn) |
| Entrez Gene | 799 (Hs), 12311 (Mm), 116506 (Rn) |
| Human Protein Atlas | ENSG00000004948 (Hs) |
| KEGG Gene | hsa:799 (Hs), mmu:12311 (Mm), rno:116506 (Rn) |
| OMIM | 114131 (Hs) |
| Pharos | P30988 (Hs) |
| RefSeq Nucleotide | NM_001742 (Hs), NM_007588 (Mm), NM_053816 (Rn), NM_001034015 (Rn) |
| RefSeq Protein | NP_001733 (Hs), NP_001158209 (Hs), NP_031614 (Mm), NP_001029187 (Rn), NP_446268 (Rn) |
| UniProtKB | P30988 (Hs), Q60755 (Mm), P32214 (Rn) |
| Wikipedia | CALCR (Hs) |
| Natural/Endogenous Ligands |
| adrenomedullin {Sp: Human} |
| adrenomedullin 2/intermedin {Sp: Human} |
| amylin {Sp: Human} , amylin {Sp: Mouse, Rat} |
| calcitonin {Sp: Human} , calcitonin {Sp: Mouse, Rat} |
| α-CGRP {Sp: Human} |
| β-CGRP {Sp: Human} , β-CGRP {Sp: Mouse} |
| α-CGRP {Sp: Mouse, Rat} |
| β-CGRP {Sp: Rat} |
| Comments: Calcitonin and amylin are the principal endogenous agonists. |
| Potency order of endogenous ligands (Human) |
| calcitonin (CALCA, P01258) ≥ amylin (IAPP, P10997), α-CGRP (CALCA, P06881), β-CGRP (CALCB, P10092) > adrenomedullin (ADM, P35318), adrenomedullin 2/intermedin (ADM2, Q7Z4H4) |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Small molecule agonists of the calcitonin receptor have also been reported, which act via the juxtamembrane region of the receptor [11]. This receptor interacts with RAMPs to form several subtypes of high affinity amylin receptor [29] (see receptor comments below) which also have significant affinity for CGRP [37]. The variability in potency values reported is likely to reflect cell background such as the presence of endogenous RAMPs. It is difficult to ascertain the contribution of such factors to the reported values. Human amylin is rarely used because of its propensity to aggregate. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| Comments: The insert positive human calcitonin receptor (hCT(b)) has altered signalling capacity. Inhibition of bone resorption by CT has been shown to be PKA dependent. | |
| References: 12,17,28 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: The insert positive human calcitonin receptor (hCT(b)) has altered signalling capacity. CT appears to stimulate this pathway in pituitary folliculo-stellate cells and hepatocytes. | |
| References: 12,20,27,40 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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| Biologically Significant Variants
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| General Comments |
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The CT receptor binds to receptor activity modifying proteins (RAMPs) to form high affinity amylin receptors[37], reviewed in [18,29]. CT and RAMP1 make up the AMY1 receptor. CT and RAMP2 make up the AMY2 receptor. CT and RAMP3 make up the AMY3 receptor. As [125I]-calcitonin (salmon) binds with high affinity to calcitonin and amylin receptors, data using this radioligand should be treated with caution. The presence of CT receptor mRNA does not explain the phenotype of the receptor that is expressed. The expression of RAMP accessory proteins must also be considered. Calcitonin receptor splice variants may be differentially expressed [12,30]. |
References
1. Albrandt K, Brady EM, Moore CX, Mull E, Sierzega ME, Beaumont K. (1995) Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene. Endocrinology, 136 (12): 5377-84. [PMID:7588285]
2. Armour SL, Foord S, Kenakin T, Chen WJ. (1999) Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor. J Pharmacol Toxicol Methods, 42 (4): 217-24. [PMID:11033437]
3. Becskei C, Riediger T, Zünd D, Wookey P, Lutz TA. (2004) Immunohistochemical mapping of calcitonin receptors in the adult rat brain. Brain Res, 1030 (2): 221-33. [PMID:15571671]
4. Chait A, Suaudeau C, De Beaurepaire R. (1995) Extensive brain mapping of calcitonin-induced anorexia. Brain Res Bull, 36: 467-472. [PMID:7712209]
5. Chausmer A, Stuart C, Stevens M. (1980) Identification of testicular cell plasma membrane receptors for calcitonin. J Lab Clin Med, 96 (5): 933-8. [PMID:6252270]
6. Chausmer AB, Stevens MD, Severn C. (1982) Autoradiographic evidence for a calcitonin receptor on testicular Leydig cells. Science, 216 (4547): 735-6. [PMID:6281881]
7. Clarke MV, Russell PK, Findlay DM, Sastra S, Anderson PH, Skinner JP, Atkins GJ, Zajac JD, Davey RA. (2015) A Role for the Calcitonin Receptor to Limit Bone Loss During Lactation in Female Mice by Inhibiting Osteocytic Osteolysis. Endocrinology, 156 (9): 3203-14. [PMID:26135836]
8. Cohen DP, Nussenzveig DR, Gershengorn MC. (1996) Iodocalcitonin binds to human calcitonin receptors with higher affinity than calcitonin. Endocrinology, 137 (10): 4507-10. [PMID:8828514]
9. Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre-Medhin S, Galson DL, Zajac JD, Karsenty G. (2004) Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol, 164 (4): 509-14. [PMID:14970190]
10. Davey RA, Turner A, McManus JF, Chiu WS, Tjahyono F, Moore AJ, Atkins GJ, Anderson PH, Ma C, Glatt V, Maclean HE, Vincent C, Bouxsein M, Morris HA, Findlay DM, Zajac JD. (2008) The Calcitonin Receptor Plays a Physiological Role to Protect Against Hypercalcemia in Mice. J Bone Miner Res, 8: 1182-1193. [PMID:18627265]
11. Dong M, Cox RF, Miller LJ. (2009) Juxtamembranous region of the amino terminus of the family B G protein-coupled calcitonin receptor plays a critical role in small-molecule agonist action. J Biol Chem, 284 (33): 21839-47. [PMID:19447889]
12. Felsenfeld AJ, Levine BS. (2015) Calcitonin, the forgotten hormone: does it deserve to be forgotten?. Clin Kidney J, 8 (2): 180-7. [PMID:25815174]
13. Galvin RJ, Bryan P, Venugopalan M, Smith DP, Thomas JE. (1998) Calcitonin responsiveness and receptor expression in porcine and murine osteoclasts: a comparative study. Bone, 23 (3): 233-40. [PMID:9737345]
14. Gingell JJ, Burns ER, Hay DL. (2014) Activity of pramlintide, rat and human amylin but not Aβ1-42 at human amylin receptors. Endocrinology, 155 (1): 21-6. [PMID:24169554]
15. Gorn AH, Rudolph SM, Flannery MR, Morton CC, Weremowicz S, Wang TZ, Krane SM, Goldring SR. (1995) 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. J Clin Invest, 95: 2680-2691. [PMID:7769107]
16. Gydesen S, Andreassen KV, Hjuler ST, Christensen JM, Karsdal MA, Henriksen K. (2016) KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight. Am J Physiol Endocrinol Metab, 310 (10): E821-7. [PMID:26908506]
17. Hay DL, Christopoulos G, Christopoulos A, Poyner DR, Sexton PM. (2005) Pharmacological discrimination of calcitonin receptor: receptor activity-modifying protein complexes. Mol Pharmacol, 67 (5): 1655-65. [PMID:15692146]
18. Hay DL, Poyner DR, Sexton PM. (2006) GPCR modulation by RAMPs. Pharmacol Ther, 109 (1-2): 173-97. [PMID:16111761]
19. Hoshiya H, Meguro M, Kashiwagi A, Okita C, Oshimura M. (2003) Calcr, a brain-specific imprinted mouse calcitonin receptor gene in the imprinted cluster of the proximal region of chromosome 6. J Hum Genet, 48 (4): 208-11. [PMID:12730726]
20. Kiriyama Y, Tsuchiya H, Murakami T, Satoh K, Tokumitsu Y. (2001) Calcitonin induces IL-6 production via both PKA and PKC pathways in the pituitary folliculo-stellate cell line. Endocrinology, 142 (8): 3563-9. [PMID:11459804]
21. Kuwasako K, Cao YN, Nagoshi Y, Tsuruda T, Kitamura K, Eto T. (2004) Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins. Mol Pharmacol, 65 (1): 207-13. [PMID:14722252]
22. Kuwasako K, Kitamura K, Nagoshi Y, Eto T. (2003) Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins. Biochem Biophys Res Commun, 301 (2): 460-4. [PMID:12565884]
23. Leuthauser K, Gujer R, Aldecoa A, McKinney RA, Muff R, Fischer JA, Born W. (2000) Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition. Biochem J, 351: 347-351. [PMID:11023820]
24. Masi L, Becherini L, Gennari L, Colli E, Mansani R, Falchetti A, Cepollaro C, Gonnelli S, Tanini A, Brandi ML. (1998) Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women. Biochem Biophys Res Commun, 245 (2): 622-6. [PMID:9571205]
25. Muff R, Bühlmann N, Fischer JA, Born W. (1999) An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Endocrinology, 140 (6): 2924-7. [PMID:10342886]
26. Nakamura M, Zhang ZQ, Shan L, Hisa T, Sasaki M, Tsukino R, Yokoi T, Kaname A, Kakudo K. (1997) Allelic variants of human calcitonin receptor in the Japanese population. Hum Genet, 99 (1): 38-41. [PMID:9003491]
27. Offermanns S, Iida-Klein A, Segre GV, Simon MI. (1996) G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells. Mol Endocrinol, 10 (5): 566-74. [PMID:8732687]
28. Pham V, Wade JD, Purdue BW, Sexton PM. (2004) Spatial proximity between a photolabile residue in position 19 of salmon calcitonin and the amino terminus of the human calcitonin receptor. J Biol Chem, 279 (8): 6720-9. [PMID:14623894]
29. Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. (2002) International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev, 54 (2): 233-46. [PMID:12037140]
30. Purdue BW, Tilakaratne N, Sexton PM. (2002) Molecular pharmacology of the calcitonin receptor. Recept Channels, 8 (3-4): 243-55. [PMID:12529940]
31. Pérez Jurado LA, Li X, Francke U. (1995) The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion associated with the Williams syndrome. Cytogenet Cell Genet, 70 (3-4): 246-9. [PMID:7789182]
32. Qi T, Dong M, Watkins HA, Wootten D, Miller LJ, Hay DL. (2013) Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Δ(1-47)hCT((a)) function. Br J Pharmacol, 168 (3): 644-57. [PMID:22946511]
33. Sexton PM, Houssami S, Hilton JM, O'Keeffe LM, Center RJ, Gillespie MT, Darcy P, Findlay DM. (1993) Identification of brain isoforms of the rat calcitonin receptor. Mol Endocrinol, 7 (6): 815-21. [PMID:8395656]
34. Sheward WJ, Lutz EM, Harmar AJ. (1994) The expression of the calcitonin receptor gene in the brain and pituitary gland of the rat. Neurosci Lett, 181 (1-2): 31-4. [PMID:7898764]
35. Sonne N, Larsen AT, Andreassen KV, Karsdal MA, Henriksen K. (2020) The Dual Amylin and Calcitonin Receptor Agonist, KBP-066, Induces an Equally Potent Weight Loss Across a Broad Dose Range While Higher Doses May Further Improve Insulin Action. J Pharmacol Exp Ther, 373 (1): 92-102. [PMID:31992608]
36. Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, de Vernejoul MC. (1998) Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet, 7 (13): 2129-33. [PMID:9817931]
37. Tilakaratne N, Christopoulos G, Zumpe ET, Foord SM, Sexton PM. (2000) Amylin receptor phenotypes derived from human calcitonin receptor/RAMP coexpression exhibit pharmacological differences dependent on receptor isoform and host cell environment. J Pharmacol Exp Ther, 294 (1): 61-72. [PMID:10871296]
38. Warshawsky H, Goltzman D, Rouleau MF, Bergeron JJ. (1980) Direct in vivo demonstration by radioautography of specific binding sites for calcitonin in skeletal and renal tissues of the rat. J Cell Biol, 85 (3): 682-94. [PMID:7391137]
39. Wolfe 3rd LA, Fling ME, Xue Z, Armour S, Kerner SA, Way J, Rimele T, Cox RF. (2003) In vitro characterization of a human calcitonin receptor gene polymorphism. Mutat Res, 522 (1-2): 93-105. [PMID:12517415]
40. Yamaguchi M. (1991) Stimulatory effect of calcitonin on Ca2+ inflow in isolated rat hepatocytes. Mol Cell Endocrinol, 75 (1): 65-70. [PMID:1646739]
41. Yamaguchi M, Watanabe Y, Ohtani T, Uezumi A, Mikami N, Nakamura M, Sato T, Ikawa M, Hoshino M, Tsuchida K et al.. (2015) Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche. Cell Rep, 13 (2): 302-14. [PMID:26440893]
42. Yamin M, Gorn AH, Flannery MR, Jenkins NA, Gilbert DJ, Copeland NG, Tapp DR, Krane SM, Goldring SR. (1994) Cloning and characterization of a mouse brain calcitonin receptor complementary deoxyribonucleic acid and mapping of the calcitonin receptor gene. Endocrinology, 135 (6): 2635-43. [PMID:7988453]
43. Zimmermann U, Fluehmann B, Born W, Fischer JA, Muff R. (1997) Coexistence of novel amylin-binding sites with calcitonin receptors in human breast carcinoma MCF-7 cells. J Endocrinol, 155 (3): 423-31. [PMID:9487987]
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