Kalcitoninu sličan receptor

Kristalografksa struktura ektodomenskog kompleksa CGRP tip 1 receptora i RAMP1.^[1]

Dostupne strukture

3AQF, 3N7P, 3N7R, 3N7S

Identifikatori

Simboli

CALCRL; CGRPR; CRLR

Vanjski ID

OMIM: 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

Vrsta

Čovek

Miš

RefSeq (mRNA)

RefSeq (protein)

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

[uredi | uredi kod]

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 G_s,^[6] koji aktivira adenilat ciklazu posledica čega je formiranje intracelularnog cikličnog adenozin monofosfata (cAMP).

Reference

[uredi | uredi kod]

↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ „Receptor properties”. SenseLab Project: Membrane properties resource. Yale University. Arhivirano iz originala na datum 2009-02-28. Pristupljeno 28. 09. 2008.

Literatura

[uredi | uredi kod]

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

[uredi | uredi kod]

„Calcitonin receptors: CALCRL”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
MeSH calcitonin+receptor-like+receptor

Transmembranski receptor: G protein spregnuti receptori

Klasa A: Rodopsinu slični

Neurotransmiter

Adrenergički	α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Purinski	Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
Serotoninski	(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

Eikozanoidni	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

Neuropeptidni

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

Orfan	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

Orfan

GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)

Drugi

Moždano specifični angiogenezni inhibitor (1, 2, 3) • Cadherin (1, 2, 3) • Kalcitonin • CALCRL • CD97 • Kortikotropin-oslobađajući hormon (1, 2) • EMR (1, 2, 3) • Glukagon (GR, GIPR, GLP1R, GLP2R) • Hormon rasta oslobađajući hormon • PACAPR1 • GPR • Latrofilin (1, 2, 3, ELTD1) • Metuselah-slični proteini • Paratiroidni hormon (1, 2) • Sekretin • Vazoaktivni intestinalni peptid (1, 2)

Klasa C: Metabotropni
glutamat / feromon

Ukus	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	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)

Neuropeptidni receptori

Hormonski receptori

Hipotalamusni	CRH - FSH - LHRH - TRH - Somatostatin
Hipofizni	Vazopresin (1A, 1B, 2) - Oksitocin - LHCG - Tip I citokinski receptor (GH, Prolaktin) - TSH
Drugi	Atrijalni natriuretski faktor (NPR1, NPR2, NPR3) - Kalcitonin - Holecistokinin (A, B) - VIP

Opioidni receptori

Delta - Kapa - Mi - Sigma (1, 2) - Nociceptin

Drugi neuropeptidni receptori

Angiotenzin - Bradikinin (B1, B2) / Tahikinin (TACR1) - Kalcitoninu sličan - Galanin - GPCR neuropeptid (B/W, FF, S, Y) - Neurotenzin