Calcitonin receptor

The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis,^[5] particularly with respect to bone formation and metabolism.^[6][7][8]

CALCR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5II0
Identifiers
Aliases	CALCR, CRT, CT-R, CTR, CTR1, calcitonin receptor
External IDs	OMIM: 114131; MGI: 101950; HomoloGene: 1320; GeneCards: CALCR; OMA:CALCR - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q21.3 Start 93,424,486 bp[1] End 93,574,730 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 A1|6 1.81 cM Start 3,685,680 bp[2] End 3,764,714 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia hypothalamus muscle of thigh human kidney placenta metanephros skeletal muscle tissue renal cortex ligament tendon Top expressed in arcuate nucleus median eminence dorsomedial hypothalamic nucleus paraventricular nucleus of hypothalamus suprachiasmatic nucleus nucleus accumbens morula lateral hypothalamus ventromedial nucleus embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity calcitonin receptor activity calcitonin binding signal transducer activity protein binding transmembrane signaling receptor activity amyloid-beta binding calcitonin gene-related peptide receptor activity amylin receptor activity Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane axon amylin receptor complex 1 amylin receptor complex 2 amylin receptor complex 3 Biological process positive regulation of adenylate cyclase activity adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of cytosolic calcium ion concentration receptor internalization response to glucocorticoid activation of phospholipase C activity activation of adenylate cyclase activity cell surface receptor signaling pathway protein transport protein localization to plasma membrane signal transduction G protein-coupled receptor signaling pathway positive regulation of gene expression positive regulation of protein kinase A signaling positive regulation of cell death positive regulation of peptidyl-serine phosphorylation cross-receptor inhibition within G protein-coupled receptor heterodimer positive regulation of protein kinase B signaling positive regulation of ERK1 and ERK2 cascade amylin receptor signaling pathway response to amyloid-beta positive regulation of calcium ion import across plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 799 12311 Ensembl ENSG00000004948 ENSMUSG00000023964 UniProt P30988 Q60755 RefSeq (mRNA) NM_001742 NM_001164737 NM_001164738 NM_001042725 NM_007588 NM_001355192 NM_001377018 RefSeq (protein) NP_001158209 NP_001158210 NP_001733 NP_001036190 NP_031614 NP_001342121 NP_001363947 Location (UCSC) Chr 7: 93.42 – 93.57 Mb Chr 6: 3.69 – 3.76 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

CT works by activating the G-proteins G_s and G_q often found on osteoclasts, on cells in the kidney, and on cells in a number of regions of the brain.^[9] It may also affect the ovaries in women and the testes in men.

The function of the CT receptor protein is modified through its interaction with Receptor activity-modifying proteins (RAMPs), forming the multimeric amylin receptors AMY₁ (CT + RAMP1), AMY₂ (CT + RAMP2), and AMY₃ (CT+ RAMP3).^[10]

Preclinical studies have suggested that dual amylin and calcitonin receptor agonists may be more effective than amylin receptor agonists for obesity and type II diabetes.^[11]

Interactions

Structure of human calcitonin recptor-G_s complex. The transmembrane calcitonin receptor (blue) is bound to human calcitonin (red) and the G_s complex (yellow). PDB: 7TYO​

Calcitonin receptor has been shown to interact with Apolipoprotein B^[12][13] and LRP1.^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000004948 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000023964 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Purdue BW, Tilakaratne N, Sexton PM (2002). "Molecular pharmacology of the calcitonin receptor". Receptors & Channels. 8 (3–4): 243–255. doi:10.1080/10606820213681. PMID 12529940.
6. Chambers TJ, Magnus CJ (January 1982). "Calcitonin alters behaviour of isolated osteoclasts". The Journal of Pathology. 136 (1): 27–39. doi:10.1002/path.1711360104. PMID 7057295. S2CID 8395420.
7. Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, et al. (February 2004). "Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo". The Journal of Cell Biology. 164 (4): 509–514. doi:10.1083/jcb.200312135. PMC 2171986. PMID 14970190.
8. Davey RA, Turner AG, McManus JF, Chiu WS, Tjahyono F, Moore AJ, et al. (August 2008). "Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice". Journal of Bone and Mineral Research. 23 (8): 1182–1193. doi:10.1359/jbmr.080310. PMC 2680171. PMID 18627265.
9. senselab Archived February 28, 2009, at the Wayback Machine
10. "Calcitonin Receptors: Introduction". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-12-12.
11. Sonne N, Karsdal MA, Henriksen K (April 2021). "Mono and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases". Molecular Metabolism. 46: 101109. doi:10.1016/j.molmet.2020.101109. PMC 8085567. PMID 33166741.
12. Zhang J, Herscovitz H (February 2003). "Nascent lipidated apolipoprotein B is transported to the Golgi as an incompletely folded intermediate as probed by its association with network of endoplasmic reticulum molecular chaperones, GRP94, ERp72, BiP, calreticulin, and cyclophilin B". The Journal of Biological Chemistry. 278 (9): 7459–7468. doi:10.1074/jbc.M207976200. PMID 12397072.
13. Linnik KM, Herscovitz H (August 1998). "Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state". The Journal of Biological Chemistry. 273 (33): 21368–21373. doi:10.1074/jbc.273.33.21368. PMID 9694898.
14. Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, et al. (June 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". The Journal of Cell Biology. 161 (6): 1179–1189. doi:10.1083/jcb.200302069. PMC 2172996. PMID 12821648.

Further reading

• Pondel M (December 2000). "Calcitonin and calcitonin receptors: bone and beyond". International Journal of Experimental Pathology. 81 (6): 405–422. doi:10.1046/j.1365-2613.2000.00176.x. PMC 2517743. PMID 11298188.
• Gorn AH, Lin HY, Yamin M, Auron PE, Flannery MR, Tapp DR, et al. (November 1992). "Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line". The Journal of Clinical Investigation. 90 (5): 1726–1735. doi:10.1172/JCI116046. PMC 443230. PMID 1331173.
• Albrandt K, Brady EM, Moore CX, Mull E, Sierzega ME, Beaumont K (December 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): 5377–5384. doi:10.1210/endo.136.12.7588285. PMID 7588285.
• Egerton M, Needham M, Evans S, Millest A, Cerillo G, McPheat J, et al. (April 1995). "Identification of multiple human calcitonin receptor isoforms: heterologous expression and pharmacological characterization". Journal of Molecular Endocrinology. 14 (2): 179–189. doi:10.1677/jme.0.0140179. PMID 7619207.
• Nussenzveig DR, Mathew S, Gershengorn MC (May 1995). "Alternative splicing of a 48-nucleotide exon generates two isoforms of the human calcitonin receptor". Endocrinology. 136 (5): 2047–2051. doi:10.1210/endo.136.5.7720653. PMID 7720653.
• Nakamura M, Hashimoto T, Nakajima T, Ichii S, Furuyama J, Ishihara Y, et al. (April 1995). "A new type of human calcitonin receptor isoform generated by alternative splicing". Biochemical and Biophysical Research Communications. 209 (2): 744–751. doi:10.1006/bbrc.1995.1562. PMID 7733946.
• 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". Cytogenetics and Cell Genetics. 70 (3–4): 246–249. doi:10.1159/000134044. PMID 7789182.
• Nussenzveig DR, Thaw CN, Gershengorn MC (November 1994). "Inhibition of inositol phosphate second messenger formation by intracellular loop one of a human calcitonin receptor. Expression and mutational analysis of synthetic receptor genes". The Journal of Biological Chemistry. 269 (45): 28123–28129. doi:10.1016/S0021-9258(18)46903-7. PMID 7961748.
• Kuestner RE, Elrod RD, Grant FJ, Hagen FS, Kuijper JL, Matthewes SL, et al. (August 1994). "Cloning and characterization of an abundant subtype of the human calcitonin receptor". Molecular Pharmacology. 46 (2): 246–255. PMID 8078488.
• Frendo JL, Pichaud F, Mourroux RD, Bouizar Z, Segond N, Moukhtar MS, et al. (April 1994). "An isoform of the human calcitonin receptor is expressed in TT cells and in medullary carcinoma of the thyroid". FEBS Letters. 342 (2): 214–216. Bibcode:1994FEBSL.342..214F. doi:10.1016/0014-5793(94)80503-2. PMID 8143880. S2CID 5709002.
• Masi L, Becherini L, Gennari L, Colli E, Mansani R, Falchetti A, et al. (April 1998). "Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women". Biochemical and Biophysical Research Communications. 245 (2): 622–626. doi:10.1006/bbrc.1998.8445. PMID 9571205.
• Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, de Vernejoul MC (December 1998). "Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women". Human Molecular Genetics. 7 (13): 2129–2133. doi:10.1093/hmg/7.13.2129. PMID 9817931.
• Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, et al. (July 1999). "Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product". Molecular Pharmacology. 56 (1): 235–242. doi:10.1124/mol.56.1.235. PMID 10385705.
• Nishikawa T, Ishikawa H, Yamamoto S, Koshihara Y (September 1999). "A novel calcitonin receptor gene in human osteoclasts from normal bone marrow". FEBS Letters. 458 (3): 409–414. Bibcode:1999FEBSL.458..409N. doi:10.1016/S0014-5793(99)01176-X. PMID 10570950. S2CID 41350895.
• Beaudreuil J, Taboulet J, Orcel P, Graulet AM, Denne MA, Baudoin C, et al. (July 2000). "Calcitonin receptor mRNA in mononuclear leucocytes from postmenopausal women: decrease during osteoporosis and link to bone markers with specific isoform involvement". Bone. 27 (1): 161–168. doi:10.1016/S8756-3282(00)00305-7. PMID 10865224.
• Wada S, Yasuda S, Nagai T, Maeda T, Kitahama S, Suda S, et al. (April 2001). "Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor". Endocrinology. 142 (4): 1471–1478. doi:10.1210/endo.142.4.8085. PMID 11250927.
• Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, et al. (September 2001). "C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells". The Journal of Experimental Medicine. 194 (6): 781–795. doi:10.1084/jem.194.6.781. PMC 2195958. PMID 11560994.
• Nosaka Y, Tachi Y, Shimpuku H, Kawamura T, Ohura K (2002). "Association of calcitonin receptor gene polymorphism with early marginal bone loss around endosseous implants". The International Journal of Oral & Maxillofacial Implants. 17 (1): 38–43. PMID 11858573.

External links

• "Calcitonin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2007-07-23.
• Calcitonin+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)