Calcium-sensing receptor

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Calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)
Identifiers
Symbols	CASR; CAR; FHH; FIH; GPRC2A; HHC; HHC1; MGC138441; NSHPT; PCAR1
External IDs	OMIM: 601199 MGI: 1351351 HomoloGene: 332 IUPHAR: CaS GeneCards: CASR Gene
Gene Ontology Molecular function • phosphoinositide phospholipase C activity • receptor activity • metabotropic glutamate, GABA-B-like receptor activity Cellular component • plasma membrane • integral to plasma membrane Biological process • ossification • detection of calcium ion • cellular calcium ion homeostasis • signal transduction • G-protein coupled receptor protein signaling pathway • chemosensory behavior • anatomical structure morphogenesis Sources: Amigo / EGO
RNA expression pattern
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More reference expression data
Orthologs
Species	Human	Mouse
Entrez	846	12374
Ensembl	ENSG00000036828	ENSMUSG00000051980
UniProt	P41180	O88982
RefSeq (mRNA)	NM_000388	NM_013803
RefSeq (protein)	NP_000379	NP_038831
Location (UCSC)	Chr 3: 123.39 - 123.49 Mb	Chr 16: 36.41 - 36.48 Mb
PubMed search	[1]	[2]

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).

Signal transduction

The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Decreased calcium binding on the extracellular side gives a conformation change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway, presumably through a G_qα type of G protein, which ultimately increases intracellular concentration of calcium, which triggers vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some sources state) the cAMP dependent pathway.

Pathology

Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia (FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment), whereas mutations that activate CASR are the cause of autosomal dominant hypocalcemia or Type 5 Bartter syndrome. An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.

Therapeutic application

The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor. It is classified as a calcimimetic, which binds to the calcium-sensing receptor and decreases parathyroid hormone release.

Interactions

Calcium-sensing receptor has been shown to interact with Filamin.

Further reading

• Hendy GN, D'Souza-Li L, Yang B; et al. (2000). "Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia". Hum. Mutat. 16 (4): 281–96. doi:10.1002/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A. PMID 11013439. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Fukumoto S (2002). "[Calcium-sensing receptor in bone cells]". Nippon Rinsho. 60 Suppl 3: 57–63. PMID 11979955. 
• Tfelt-Hansen J, Schwarz P, Brown EM, Chattopadhyay N (2004). "The calcium-sensing receptor in human disease". Front. Biosci. 8: s377–90. doi:10.2741/1068. PMID 12700051. CS1 maint: Multiple names: authors list (link)
• Hu J, Spiegel AM (2004). "Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function". Trends Endocrinol. Metab. 14 (6): 282–8. PMID 12890593. 
• Aida K, Koishi S, Inoue M; et al. (1995). "Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene". J. Clin. Endocrinol. Metab. 80 (9): 2594–8. doi:10.1210/jc.80.9.2594. PMID 7673400. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Aida K, Koishi S, Tawata M, Onaya T (1995). "Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney". Biochem. Biophys. Res. Commun. 214 (2): 524–9. doi:10.1006/bbrc.1995.2318. PMID 7677761. CS1 maint: Multiple names: authors list (link)
• Chou YH, Pollak MR, Brandi ML; et al. (1995). "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia". Am. J. Hum. Genet. 56 (5): 1075–9. PMC 1801464 Freely accessible. PMID 7726161. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Garrett JE, Capuano IV, Hammerland LG; et al. (1995). "Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs". J. Biol. Chem. 270 (21): 12919–25. doi:10.1074/jbc.270.21.12919. PMID 7759551. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Pollak MR, Brown EM, Estep HL; et al. (1995). "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation". Nat. Genet. 8 (3): 303–7. doi:10.1038/ng1194-303. PMID 7874174. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Pollak MR, Brown EM, Chou YH; et al. (1994). "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism". Cell. 75 (7): 1297–303. doi:10.1016/0092-8674(93)90617-Y. PMID 7916660. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Janicic N, Soliman E, Pausova Z; et al. (1996). "Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16". Mamm. Genome. 6 (11): 798–801. doi:10.1007/BF00539007. PMID 8597637. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bikle DD, Ratnam A, Mauro T; et al. (1996). "Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor". J. Clin. Invest. 97 (4): 1085–93. doi:10.1172/JCI118501. PMC 507156 Freely accessible. PMID 8613532. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Pearce SH, Trump D, Wooding C; et al. (1996). "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism". J. Clin. Invest. 96 (6): 2683–92. doi:10.1172/JCI118335. PMC 185975 Freely accessible. PMID 8675635. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bai M, Quinn S, Trivedi S; et al. (1996). "Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor". J. Biol. Chem. 271 (32): 19537–45. doi:10.1074/jbc.271.32.19537. PMID 8702647. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Baron J, Winer KK, Yanovski JA; et al. (1997). "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism". Hum. Mol. Genet. 5 (5): 601–6. doi:10.1093/hmg/5.5.601. PMID 8733126. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Freichel M, Zink-Lorenz A, Holloschi A; et al. (1996). "Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion". Endocrinology. 137 (9): 3842–8. doi:10.1210/en.137.9.3842. PMID 8756555. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Chattopadhyay N, Ye C, Singh DP; et al. (1997). "Expression of extracellular calcium-sensing receptor by human lens epithelial cells". Biochem. Biophys. Res. Commun. 233 (3): 801–5. doi:10.1006/bbrc.1997.6553. PMID 9168937. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Cole DE, Janicic N, Salisbury SR, Hendy GN (1997). "Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium-sensing receptor gene". Am. J. Med. Genet. 71 (2): 202–10. doi:10.1002/(SICI)1096-8628(19970808)71:2<202::AID-AJMG16>3.0.CO;2-I. PMID 9217223. CS1 maint: Multiple names: authors list (link)
• Ward BK, Stuckey BG, Gutteridge DH; et al. (1997). "A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia". Hum. Mutat. 10 (3): 233–5. doi:10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J. PMID 9298824. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Quinn SJ, Kifor O, Trivedi S; et al. (1998). "Sodium and ionic strength sensing by the calcium receptor". J. Biol. Chem. 273 (31): 19579–86. doi:10.1074/jbc.273.31.19579. PMID 9677383. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• "Calcium-Sensing Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
• CASRdb - Calcium Sensing Receptor Database, McGill University
• MeSH Receptors,+Calcium-Sensing
• MeSH CASR+protein

de:Calciumsensitiver Rezeptor ja:カルシウム感知受容体