Calcium-sensing receptor

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Calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)
Identifiers
Symbol(s) CASR; CAR; FHH; FIH; GPRC2A; HHC; HHC1; MGC138441; NSHPT; PCAR1
External IDs OMIM: 601199 MGI: 1351351 HomoloGene: 332
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 846 12374
Ensembl ENSG00000036828 ENSMUSG00000051980
Uniprot P41180 O88982
Refseq NM_000388 (mRNA)
NP_000379 (protein)		 NM_013803 (mRNA)
NP_038831 (protein)
Location 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.[1]

Contents

[edit] Pathology

Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia (FHH),[2] whereas mutations that activate CASR are the cause of autosomal dominant hypocalcemia.[3] An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.[4]

[edit] Therapeutic application

The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[5]

[edit] References

  1. ^ D'Souza-Li L (2006). "The calcium-sensing receptor and related diseases". Arquivos brasileiros de endocrinologia e metabologia 50 (4): 628–39. doi:10.1590/S0004-27302006000400008. PMID 17117288. 
  2. ^ Pidasheva S, Canaff L, Simonds WF, Marx SJ, Hendy GN (2005). "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia". Hum. Mol. Genet. 14 (12): 1679–90. doi:10.1093/hmg/ddi176. PMID 15879434. 
  3. ^ Mancilla EE, De Luca F, Baron J (1998). "Activating mutations of the Ca2+-sensing receptor". Mol. Genet. Metab. 64 (3): 198–204. doi:10.1006/mgme.1998.2716. PMID 9719629. 
  4. ^ Entrez Gene: CASR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism).
  5. ^ Torres PU (2006). "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 16 (3): 253–8. doi:10.1053/j.jrn.2006.04.010. PMID 16825031. 

[edit] 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. 
  • 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. PMID 12700051. 
  • 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. PMID 7673400. 
  • 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. 
  • 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. PMID 7726161. 
  • 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. PMID 7759551. 
  • 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. 
  • 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. PMID 7916660. 
  • 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. PMID 8597637. 
  • 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. PMID 8613532. 
  • 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. PMID 8675635. 
  • 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. PMID 8702647. 
  • 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. PMID 8733126. 
  • 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. PMID 8756555. 
  • 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. 
  • 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. PMID 9217223. 
  • 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. 
  • 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. PMID 9677383. 

[edit] External links

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Transmembrane receptor: G protein-coupled receptors
Class A: Rhodopsin like
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Class B: Secretin like
Class C: Metabotropic
glutamate / pheromone
Calcium-sensing receptor - GABA B (1, 2) - Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) - GPRC6A - GPR (156, 158, 179) - RAIG (1, 2, 3, 4) - Taste receptors (TAS1R (1, 2, 3) TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50))
Frizzled / Smoothened
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - Smoothened