Calcitonin receptor

Protein-coding gene in the species Homo sapiens
CALCR
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

5II0

Identifiers
AliasesCALCR, CRT, CT-R, CTR, CTR1, calcitonin receptor
External IDsOMIM: 114131 MGI: 101950 HomoloGene: 1320 GeneCards: CALCR
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for CALCR
Genomic location for CALCR
Band7q21.3Start93,424,486 bp[1]
End93,574,730 bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for CALCR
Genomic location for CALCR
Band6 A1|6 1.81 cMStart3,685,680 bp[2]
End3,764,714 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • tibia

  • hypothalamus

  • kidney

  • placenta

  • metanephros

  • skeletal muscle tissue

  • renal cortex

  • ligament

  • tendon

  • islet of Langerhans
Top expressed in
  • arcuate nucleus

  • median eminence

  • dorsomedial hypothalamic nucleus

  • paraventricular nucleus of hypothalamus

  • suprachiasmatic nucleus

  • nucleus accumbens

  • lateral hypothalamus

  • ventromedial nucleus

  • morula

  • dorsal tegmental nucleus
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
SpeciesHumanMouse
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 MbChr 6: 3.69 – 3.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

CT works by activating the G-proteins Gs and Gq 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-Gs complex. The transmembrane calcitonin receptor (blue) is bound to human calcitonin (red) and the Gs complex (yellow). PDB: 7TYO​

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000004948 – Ensembl, May 2017
  2. ^ a b c 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): 243–55. 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, Gebre-Medhin S, Galson DL, Zajac JD, Karsenty G (February 2004). "Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo". The Journal of Cell Biology. 164 (4): 509–14. doi:10.1083/jcb.200312135. PMC 2171986. PMID 14970190.
  8. ^ Davey RA, Turner AG, 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 (August 2008). "Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice". Journal of Bone and Mineral Research. 23 (8): 1182–93. 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 (1 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. ISSN 2212-8778. 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): 7459–68. 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): 21368–73. doi:10.1074/jbc.273.33.21368. PMID 9694898.
  14. ^ Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, Murphy-Ullrich JE (June 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". The Journal of Cell Biology. 161 (6): 1179–89. 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): 405–22. 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, Manning CA, Lodish HF, Krane SM, Goldring SR (November 1992). "Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line". The Journal of Clinical Investigation. 90 (5): 1726–35. 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): 5377–84. doi:10.1210/endo.136.12.7588285. PMID 7588285.
  • Egerton M, Needham M, Evans S, Millest A, Cerillo G, McPheat J, Popplewell M, Johnstone D, Hollis M (April 1995). "Identification of multiple human calcitonin receptor isoforms: heterologous expression and pharmacological characterization". Journal of Molecular Endocrinology. 14 (2): 179–89. 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): 2047–51. doi:10.1210/endo.136.5.7720653. PMID 7720653.
  • Nakamura M, Hashimoto T, Nakajima T, Ichii S, Furuyama J, Ishihara Y, Kakudo K (April 1995). "A new type of human calcitonin receptor isoform generated by alternative splicing". Biochemical and Biophysical Research Communications. 209 (2): 744–51. 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): 246–9. 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): 28123–9. doi:10.1016/S0021-9258(18)46903-7. PMID 7961748.
  • Kuestner RE, Elrod RD, Grant FJ, Hagen FS, Kuijper JL, Matthewes SL, O'Hara PJ, Sheppard PO, Stroop SD, Thompson DL (August 1994). "Cloning and characterization of an abundant subtype of the human calcitonin receptor". Molecular Pharmacology. 46 (2): 246–55. PMID 8078488.
  • Frendo JL, Pichaud F, Mourroux RD, Bouizar Z, Segond N, Moukhtar MS, Jullienne A (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): 214–6. doi:10.1016/0014-5793(94)80503-2. PMID 8143880. S2CID 5709002.
  • Masi L, Becherini L, Gennari L, Colli E, Mansani R, Falchetti A, Cepollaro C, Gonnelli S, Tanini A, Brandi ML (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): 622–6. 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): 2129–33. doi:10.1093/hmg/7.13.2129. PMID 9817931.
  • Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, Sexton PM (July 1999). "Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product". Molecular Pharmacology. 56 (1): 235–42. 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): 409–14. doi:10.1016/S0014-5793(99)01176-X. PMID 10570950. S2CID 41350895.
  • Beaudreuil J, Taboulet J, Orcel P, Graulet AM, Denne MA, Baudoin C, Jullienne A, De Vernejoul MC (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): 161–8. doi:10.1016/S8756-3282(00)00305-7. PMID 10865224.
  • Wada S, Yasuda S, Nagai T, Maeda T, Kitahama S, Suda S, Findlay DM, Iitaka M, Katayama S (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): 1471–8. doi:10.1210/endo.142.4.8085. PMID 11250927.
  • Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, Henson PM (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): 781–95. 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.
  • Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

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)
  • v
  • t
  • e
Neurotransmitter
Adrenergic
Purinergic
Serotonin
Other
Metabolites and
signaling molecules
Eicosanoid
Other
Peptide
Neuropeptide
Other
Miscellaneous
Taste, bitter
Orphan
Other
Adhesion
Orphan
Other
Taste, sweet
Other
Class F: Frizzled & Smoothened
Frizzled
Smoothened