Kalcijum-detektujući receptor

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
Vrsta	Čovek
Entrez	846
Ensembl	ENSG00000036828
UniProt	P41180
RefSeq (mRNA)	NM_000388.3
RefSeq (protein)	NP_000379.2
Lokacija (UCSC)	Chr 3:; 121.9 - 122.01 Mb
PubMed pretraga	[1]

Kalcijum-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 kao odgovor na uvećanje 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. PMID 17117288. doi:10.1590/S0004-27302006000400008.
^ InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009
^ ^а ^б Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (1999). „Calcium-sensing receptor and calcimimetic agents”. Kidney Int. Suppl. 73: S52—8. PMID 10633465.
^ Costanzo, Linda S. (2007). Physiology (Board Review Series). стр. 260. ISBN 978-0-7817-7311-9.
^ Hjälm, G; MacLeod R J; et al. (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. ISSN 0021-9258. PMID 11390380. doi:10.1074/jbc.M100784200.
^ Awata, H; Huang C; et al. (2001). „Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein”. J. Biol. Chem. United States. 276 (37): 34871—9. ISSN 0021-9258. PMID 11390379. doi:10.1074/jbc.M100775200.

Literatura

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. PMID 11013439. doi:10.1002/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A.
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. doi:10.2741/1068.
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. doi:10.1210/jc.80.9.2594.
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. PMID 7677761. doi:10.1006/bbrc.1995.2318.
Chou YH; Pollak MR; Brandi ML; et al. (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; et al. (1995). „Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs”. J. Biol. Chem. 270 (21): 12919—25. PMID 7759551. doi:10.1074/jbc.270.21.12919.
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. PMID 7874174. doi:10.1038/ng1194-303.
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. doi:10.1016/0092-8674(93)90617-Y.
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. doi:10.1007/BF00539007.
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. PMC 507156  . PMID 8613532. doi:10.1172/JCI118501.
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. PMC 185975  . PMID 8675635. doi:10.1172/JCI118335.
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. doi:10.1074/jbc.271.32.19537.
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. doi:10.1093/hmg/5.5.601.
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. doi:10.1210/en.137.9.3842.
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. PMID 9168937. doi:10.1006/bbrc.1997.6553.
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. doi:10.1002/(SICI)1096-8628(19970808)71:2<202::AID-AJMG16>3.0.CO;2-I.
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. PMID 9298824. doi:10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J.
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. doi:10.1074/jbc.273.31.19579.
Magno AL, Ward BK, Ratajczak T (2011). „The calcium-sensing receptor: a molecular Perspective”. Endocr Rev. 32 (1): 3—30. PMID 20729338. doi:10.1210/er.2009-0043.

Spoljašnje veze

„Calcium-Sensing Receptors”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 03. 03. 2016. г.
CASRdb - Calcium Sensing Receptor Database
Receptors,+Calcium-Sensing на US National Library of Medicine Medical Subject Headings (MeSH)
CASR+protein на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid17117288-1] D'Souza-Li L (2006). „The calcium-sensing receptor and related diseases”. Arquivos brasileiros de endocrinologia e metabologia. 50 (4): 628—39. PMID 17117288. doi:10.1590/S0004-27302006000400008.

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

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

[brs-4] Costanzo, Linda S. (2007). Physiology (Board Review Series). стр. 260. ISBN 978-0-7817-7311-9.

[pmid11390380-5] Hjälm, G; MacLeod R J; et al. (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. ISSN 0021-9258. PMID 11390380. doi:10.1074/jbc.M100784200.

[pmid11390379-6] Awata, H; Huang C; et al. (2001). „Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein”. J. Biol. Chem. United States. 276 (37): 34871—9. ISSN 0021-9258. PMID 11390379. doi:10.1074/jbc.M100775200.

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