Kalcijum-detektujući receptor

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Kalcijum-detektujući receptor‎‎
Identifikatori
SimboliCASR; CAR; EIG8; FHH; FIH; GPRC2A; HHC; HHC1; NSHPT; PCAR1
Vanjski IDOMIM: 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
VrstaČovekMiš
Entrez84612374
EnsemblENSG00000036828ENSMUSG00000051980
UniProtP41180Q9QY96
RefSeq (mRNA)NM_000388.3NM_013803.2
RefSeq (protein)NP_000379.2NP_038831.2
Lokacija (UCSC)Chr 3:
121.9 - 122.01 Mb		Chr 16:
36.49 - 36.56 Mb
PubMed pretraga[1][2]

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 Gqα 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

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

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. 
  • Pollak MR, Brown EM, Estep HL i dr.. (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 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
  • p
  • r
  • u
Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • GPR (156, 158, 179) • RAIG (1, 2, 3, 4)
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)