Kalcijum-detektujući receptor

Kalcijum-detektujući receptor‎‎
Identifikatori
Simboli	CASR; CAR; EIG8; FHH; FIH; GPRC2A; HHC; HHC1; NSHPT; PCAR1
Vanjski ID	OMIM: 601199 MGI: 1351351 HomoloGene: 332 IUPHAR: CaS GeneCards: CASR Gene
Ontologija gena
Molekularna funkcija	• aktivnost fosfatidilinozitol fosfolipaze C; • aktivnost G-protein spregnutog receptora; • proteinsko vezivanje;
Celularna komponenta	• ćelijska membrana; • integralno sa ćelijskom membranom;
Biološki proces	• osifikacija; • detekcija jona kalcijuma; • homeostaza ćelijskih jona kalcijuma; • signalni put G-protein spregnutog receptora; • hemosensorno ponašanje; • anatomiska struktura morfogeneze;
Pregled RNK izražavanja
	podaci
Ortolozi

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PKalcijum-detektujući receptor (CaSR) je G protein spregnuti receptor klase C koji reaguje na promene ekstracelularnih nivoa jona kalcijuma. U paraštitnoj žlezdi, kalcijum-detektujući receptor kontroliše homeostazu kalcijuma putem regulacije otpuštanja paratiroidnog hormona (PTH).^[1]

Prenos signala

Otpuštanje PTH je inhibirano u responsu na povišenje koncentracije kalcijuma u plazmi i time uzrokovanu aktivaciju kalciumskog receptora. Povećano vezivanje kalcijuma na ekstracelularnoj strani proizvodi konformacione promene receptora, te na intracelularnoj strani dolazi do inicijacije puta fosfolipaze C,^[2]^[3] putem G_qα tipa G proteina, što ultimatno povišava intracelularnu koncentraciju kalcijuma. Time se inhibira fuzija vezikula i eksocitoza paratiroidnog hormona. On takođe inhibira cAMP zavisni put^[3], mada neki izvori navode suprotno dejstvo.^[4])

Interakcije

Kalcijum-detektujući receptor formira interakcije sa filaminom.^[5]^[6]

Reference

↑ 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.
↑ InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009
↑ ^3,0 ^3,1 Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (December 1999). „Calcium-sensing receptor and calcimimetic agents”. Kidney Int. Suppl. 73: S52–8. PMID 10633465.
↑ Costanzo, Linda S. (2007). str. 260. ISBN 978-0-7817-7311-9.
↑ Hjälm, G; MacLeod R J, Kifor O, Chattopadhyay N, Brown E M (September 2001). „Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase”. J. Biol. Chem. (United States) 276 (37): 34880–7. DOI:10.1074/jbc.M100784200. ISSN 0021-9258. PMID 11390380.
↑ Awata, H; Huang C, Handlogten M E, Miller R T (September 2001). „Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein”. J. Biol. Chem. (United States) 276 (37): 34871–9. DOI:10.1074/jbc.M100775200. ISSN 0021-9258. PMID 11390379.

Literatura

Hendy GN, D'Souza-Li L, Yang B i dr.. (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. DOI:10.2741/1068. 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 i dr.. (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.
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 i dr.. (1995). „Mutations in the Human Ca2+-Sensing-Receptor Gene That Cause Familial Hypocalciuric Hypercalcemia”. Am. J. Hum. Genet. 56 (5): 1075–9. PMC 1801464. PMID 7726161.
Garrett JE, Capuano IV, Hammerland LG i dr.. (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.
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Pollak MR, Brown EM, Chou YH i dr.. (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.
Janicic N, Soliman E, Pausova Z i dr.. (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.
Bikle DD, Ratnam A, Mauro T i dr.. (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. PMID 8613532.
Pearce SH, Trump D, Wooding C i dr.. (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. PMID 8675635.
Bai M, Quinn S, Trivedi S i dr.. (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.
Baron J, Winer KK, Yanovski JA i dr.. (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.
Freichel M, Zink-Lorenz A, Holloschi A i dr.. (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.
Chattopadhyay N, Ye C, Singh DP i dr.. (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. DOI:10.1002/(SICI)1096-8628(19970808)71:2<202::AID-AJMG16>3.0.CO;2-I. PMID 9217223.
Ward BK, Stuckey BG, Gutteridge DH i dr.. (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 i dr.. (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.
Magno AL, Ward BK, Ratajczak T, (2011). „The calcium-sensing receptor: a molecular Perspective”. Endocr Rev. 32 (1): 3–30. DOI:10.1210/er.2009-0043. PMID 20729338.
Costanzo, Linda S. (2007). str. 260. ISBN 978-0-7817-7311-9.

Spoljašnje veze

„Calcium-Sensing Receptors”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-03.
CASRdb - Calcium Sensing Receptor Database
MeSH Receptors,+Calcium-Sensing
MeSH CASR+protein

[pmid17117288-1] 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] InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009

[coburn-3] 3,0 ^3,1 Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (December 1999). „Calcium-sensing receptor and calcimimetic agents”. Kidney Int. Suppl. 73: S52–8. PMID 10633465.

[brs-4] Costanzo, Linda S. (2007). str. 260. ISBN 978-0-7817-7311-9.

[pmid11390380-5] Hjälm, G; MacLeod R J, Kifor O, Chattopadhyay N, Brown E M (September 2001). „Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase”. J. Biol. Chem. (United States) 276 (37): 34880–7. DOI:10.1074/jbc.M100784200. ISSN 0021-9258. PMID 11390380.

[pmid11390379-6] Awata, H; Huang C, Handlogten M E, Miller R T (September 2001). „Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein”. J. Biol. Chem. (United States) 276 (37): 34871–9. DOI:10.1074/jbc.M100775200. ISSN 0021-9258. PMID 11390379.

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