CALCRL

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Kalcitoninu sličan receptor

Kristalografksa struktura ektodomenskog kompleksa CGRP tip 1 receptora i RAMP1.[1]
Dostupne strukture
3AQF, 3N7P, 3N7R, 3N7S
Identifikatori
SimboliCALCRL; CGRPR; CRLR
Vanjski IDOMIM: 114190 MGI: 1926944 HomoloGene: 21179 IUPHAR: CALCRL GeneCards: CALCRL Gene
Ontologija gena
Molekularna funkcija • aktivnost adrenomedulinskog receptora
• aktivnost kalcitoninu sličnog receptora
• aktivnost G-protein spregnutog receptora
Celularna komponenta • lizozom
• endozom
• endoplaszmični retikulum
• ćelijska membrana
Biološki proces • angiogeneza
• cAMP biosintetički proces
• transport kalcijumskih jona
• regulacija mišićne kontrakcije
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez1020354598
EnsemblENSG00000064989ENSMUSG00000059588
UniProtQ16602Q9R1W5
RefSeq (mRNA)NM_005795.4NM_018782.2
RefSeq (protein)NP_005786.1NP_061252.2
Lokacija (UCSC)Chr 2:
188.21 - 188.31 Mb		Chr 2:
84.17 - 84.27 Mb
PubMed pretraga[1][2]

Kalcitoninskom receptoru sličan receptor (CALCRL, CRLR) je ljudski protein.[2]

Funkcija

Ovaj protein je G protein spregnuti receptor, koji je srodan sa kalcitoninskim receptorom. CALCRL je vezan za jedan od tri jednoprolazna transmembranska domena modifikujućeg protena receptorske aktivnosti (RAMP) koji su esencijalni ja njegovo dejstvo.

Asocijacija CALCRL sa različitim RAMP proteinima proizvodi različite receptore:[3][4]

  • sa RAMP1: proizvodi CGRP receptor
  • sa RAMP2: proizvodi adrenomedullinski (AM) receptor, koji je označava AM1[5]
  • sa RAMP3: proizvodi dvojni CGRP/AM receptor, sa oznakom AM2

Ti receptori formiraju interakcije sa G proteinom Gs,[6] koji aktivira adenilat ciklazu posledica čega je formiranje intracelularnog cikličnog adenozin monofosfata (cAMP).

Reference

  1. ↑ PDB 3N7S; ter Haar E, Koth CM, Abdul-Manan N, Swenson L, Coll JT, Lippke JA, Lepre CA, Garcia-Guzman M, Moore JM (September 2010). „Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism”. Structure 18 (9): 1083–93. DOI:10.1016/j.str.2010.05.014. PMID 20826335. 
  2. ↑ Aiyar N, Rand K, Elshourbagy NA, Zeng Z, Adamou JE, Bergsma DJ, Li Y (May 1996). „A cDNA encoding the calcitonin gene-related peptide type 1 receptor”. J. Biol. Chem. 271 (19): 11325–9. DOI:10.1074/jbc.271.19.11325. PMID 8626685. 
  3. ↑ McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM (May 1998). „RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor”. Nature 393 (6683): 333–9. DOI:10.1038/30666. PMID 9620797. 
  4. ↑ Foord SM, Marshall FH (May 1999). „RAMPs: accessory proteins for seven transmembrane domain receptors”. Trends Pharmacol. Sci. 20 (5): 184–7. DOI:10.1016/S0165-6147(99)01347-4. PMID 10354609. 
  5. ↑ Kamitani S, Asakawa M, Shimekake Y, Kuwasako K, Nakahara K, Sakata T (April 1999). „The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells”. FEBS Lett. 448 (1): 111–4. DOI:10.1016/S0014-5793(99)00358-0. PMID 10217420. 
  6. ↑ „Receptor properties”. SenseLab Project: Membrane properties resource. Yale University. Arhivirano iz originala na datum 2009-02-28. Pristupljeno 28. 09. 2008. 

Literatura

  • Born W, Muff R, Fischer JA (2002). „Functional interaction of G protein-coupled receptors of the adrenomedullin peptide family with accessory receptor-activity-modifying proteins (RAMP).”. Microsc. Res. Tech. 57 (1): 14–22. DOI:10.1002/jemt.10051. PMID 11921352. 
  • Yallampalli C, Chauhan M, Thota CS, et al. (2003). „Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity.”. Trends Endocrinol. Metab. 13 (6): 263–9. PMID 12128288. 
  • Foord SM, Craig RK (1988). „Isolation and characterisation of a human calcitonin-gene-related-peptide receptor.”. Eur. J. Biochem. 170 (1-2): 373–9. DOI:10.1111/j.1432-1033.1987.tb13710.x. PMID 2826160. 
  • Skofitsch G, Jacobowitz DM (1986). „Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system.”. Peptides 6 (5): 975–86. DOI:10.1016/0196-9781(85)90331-6. PMID 3001670. 
  • Flühmann B, Muff R, Hunziker W, et al. (1995). „A human orphan calcitonin receptor-like structure.”. Biochem. Biophys. Res. Commun. 206 (1): 341–7. DOI:10.1006/bbrc.1995.1047. PMID 7818539. 
  • Aiyar N, Rand K, Elshourbagy NA, et al. (1996). „A cDNA encoding the calcitonin gene-related peptide type 1 receptor.”. J. Biol. Chem. 271 (19): 11325–9. DOI:10.1074/jbc.271.19.11325. PMID 8626685. 
  • McLatchie LM, Fraser NJ, Main MJ, et al. (1998). „RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.”. Nature 393 (6683): 333–9. DOI:10.1038/30666. PMID 9620797. 
  • Sams A, Jansen-Olesen I (1999). „Expression of calcitonin receptor-like receptor and receptor-activity-modifying proteins in human cranial arteries.”. Neurosci. Lett. 258 (1): 41–4. DOI:10.1016/S0304-3940(98)00844-1. PMID 9876047. 
  • Kamitani S, Asakawa M, Shimekake Y, et al. (1999). „The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.”. FEBS Lett. 448 (1): 111–4. DOI:10.1016/S0014-5793(99)00358-0. PMID 10217420. 
  • Aldecoa A, Gujer R, Fischer JA, Born W (2000). „Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells.”. FEBS Lett. 471 (2-3): 156–60. DOI:10.1016/S0014-5793(00)01387-9. PMID 10767413. 
  • Frayon S, Cueille C, Gnidéhou S, et al. (2000). „Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells.”. Biochem. Biophys. Res. Commun. 270 (3): 1063–7. DOI:10.1006/bbrc.2000.2552. PMID 10772950. 
  • Kuwasako K, Shimekake Y, Masuda M, et al. (2000). „Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling.”. J. Biol. Chem. 275 (38): 29602–9. DOI:10.1074/jbc.M004534200. PMID 10882736. 
  • Evans BN, Rosenblatt MI, Mnayer LO, et al. (2000). „CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors.”. J. Biol. Chem. 275 (40): 31438–43. DOI:10.1074/jbc.M005604200. PMID 10903324. 
  • Hilairet S, Foord SM, Marshall FH, Bouvier M (2001). „Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins.”. J. Biol. Chem. 276 (31): 29575–81. DOI:10.1074/jbc.M102722200. PMID 11387328. 
  • Kamitani S, Sakata T (2001). „Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling.”. Biochim. Biophys. Acta 1539 (1-2): 131–9. DOI:10.1016/S0167-4889(01)00100-8. PMID 11389975. 
  • Nikitenko LL, Brown NS, Smith DM, et al. (2001). „Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus.”. Mol. Hum. Reprod. 7 (7): 655–64. DOI:10.1093/molehr/7.7.655. PMID 11420389. 
  • Hilairet S, Bélanger C, Bertrand J, et al. (2001). „Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin.”. J. Biol. Chem. 276 (45): 42182–90. DOI:10.1074/jbc.M107323200. PMID 11535606. 
  • Aiyar N, Disa J, Pullen M, Nambi P (2002). „Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells.”. Mol. Cell. Biochem. 224 (1-2): 123–33. DOI:10.1023/A:1011907328682. PMID 11693189. 
  • Hagner S, Haberberger RV, Overkamp D, et al. (2002). „Expression and distribution of calcitonin receptor-like receptor in human hairy skin.”. Peptides 23 (1): 109–16. DOI:10.1016/S0196-9781(01)00586-1. PMID 11814625. 

Spoljašnje veze

  • „Calcitonin receptors: CALCRL”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
  • MeSH calcitonin+receptor-like+receptor
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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
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)
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Neuropeptidni receptori
Hormonski receptori
Drugi
Opioidni receptori
Drugi neuropeptidni receptori
Angiotenzin - Bradikinin (B1, B2) / Tahikinin (TACR1) - Kalcitoninu sličan - Galanin - GPCR neuropeptid (B/W, FF, S, Y) - Neurotenzin
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)