Glukagonski receptor

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Glukagonski receptor
Dostupne strukture
3CZF
Identifikatori
SimboliGCGR; GGR
Vanjski IDOMIM: 138033 MGI: 99572 HomoloGene: 131 IUPHAR: glucagon GeneCards: GCGR Gene
Ontologija gena
Molekularna funkcija • aktivnost glukagonskog receptora
• aktivnost faktora razmene guanil nukleotida
• vezivanje peptidnog hormona
Celularna komponenta • endozom
• ćelijska membrana
• integralno sa membranom
Biološki proces • formiranje prekursornih metabolita i energije
• metabolički proces energijske rezerve
• eksocitoza
• signalni put adenilat ciklazom posredovanog G protein spregnutog receptora
Ortolozi
VrstaČovekMiš
Entrez264214527
EnsemblENSG00000215644ENSMUSG00000025127
UniProtP47871Q61606
RefSeq (mRNA)NM_000160.3NM_008101.2
RefSeq (protein)NP_000151.1NP_032127.2
Lokacija (UCSC)Chr 17:
79.76 - 79.77 Mb		Chr 11:
120.39 - 120.4 Mb
PubMed pretraga[1][2]

Glukagonski receptor je 62 kDa težak protein koji se aktivira glukagonom. On je član klase B G protein spregnutih receptora. On formira spregu sa G alfa i, Gs i u manjoj meri G alfa q.[1] Stimulacija receptora dovodi do aktivacije adenilat ciklaze i povišenja nivoa intracelularnog cAMP. Kod ljudi, glukagonski receptor je kodiran GCGR genom.[2][3]

Glukagonski receptori su uglavnom izraženi u jetri i bugrezima, i u manjim razmeri u srcu, adipoznom tkivu, slezini, grudnoj žledi, nadbubrežnim žlezdama, pankreasu, cerebralnom korteksu, i gastrointestinalnom traktu.

Klinički zanačaj

Jedna od mutacija GCGR gena je vezana za dijabetes melitus tip 2.[4]

Inaktivirajuća mutacija glukagonskog receptora kod ljudi uzrokuje otpornost na glukagon, te je povezana sa hiperplazijom pankreasnih alfa ćelija, nezidioblastozom, hiperglukagonemijom, i pankreasnim neuroendokrinim tumorima.[5]

Reference

  1. ↑ Brubaker PL, Drucker DJ (2002). „Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors”. Recept. Channels 8 (3-4): 179–88. DOI:10.1080/10606820213687. PMID 12529935. 
  2. ↑ Lok S, Kuijper JL, Jelinek LJ, Kramer JM, Whitmore TE, Sprecher CA, Mathewes S, Grant FJ, Biggs SH, Rosenberg GB (March 1994). „The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization”. Gene 140 (2): 203–9. DOI:10.1016/0378-1119(94)90545-2. PMID 8144028. 
  3. ↑ Menzel S, Stoffel M, Espinosa R, Fernald AA, Le Beau MM, Bell GI (March 1994). „Localization of the glucagon receptor gene to human chromosome band 17q25”. Genomics 20 (2): 327–8. DOI:10.1006/geno.1994.1179. PMID 8020989. 
  4. ↑ Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C (March 1995). „A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus”. Nat. Genet. 9 (3): 299–304. DOI:10.1038/ng0395-299. PMID 7773293. 
  5. ↑ Zhou C, Dhall D, Nissen NN, Chen CR, Yu R (2009). „Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor.”. Pancreas 38 (8): 941–6. DOI:10.1097/MPA.0b013e3181b2bb03. PMC 2767399. PMID 19657311. 

Literatura

  • Levey GS, Weiss SR, Ruiz E (1975). „Characterization of the glucagon receptor in a pheochromocytoma.”. J. Clin. Endocrinol. Metab. 40 (4): 720–3. DOI:10.1210/jcem-40-4-720. PMID 165216. 
  • Nakamura S, Rodbell M (1991). „Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes.”. Proc. Natl. Acad. Sci. U.S.A. 88 (16): 7150–4. DOI:10.1073/pnas.88.16.7150. PMC 52251. PMID 1908089. 
  • Horuk R, Wright DE (1983). „Partial purification and characterization of the glucagon receptor.”. FEBS Lett. 155 (2): 213–7. DOI:10.1016/0014-5793(82)80605-4. PMID 6303843. 
  • MacNeil DJ, Occi JL, Hey PJ, et al. (1994). „Cloning and expression of a human glucagon receptor.”. Biochem. Biophys. Res. Commun. 198 (1): 328–34. DOI:10.1006/bbrc.1994.1046. PMID 7507321. 
  • Fujisawa T, Ikegami H, Yamato E, et al. (1995). „A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus.”. Diabetologia 38 (8): 983–5. DOI:10.1007/BF00400589. PMID 7589886. 
  • Unson CG, Macdonald D, Merrifield RB (1993). „The role of histidine-1 in glucagon action.”. Arch. Biochem. Biophys. 300 (2): 747–50. DOI:10.1006/abbi.1993.1103. PMID 8382034. 
  • Chambers SM, Morris BJ (1996). „Glucagon receptor gene mutation in essential hypertension.”. Nat. Genet. 12 (2): 122. DOI:10.1038/ng0296-122. PMID 8563746. 
  • Yamato E, Ikegami H, Takekawa K, et al. (1997). „Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1).”. Horm. Metab. Res. 29 (2): 56–9. DOI:10.1055/s-2007-978985. PMID 9105899. 
  • Strazzullo P, Iacone R, Siani A, et al. (2001). „Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.”. J. Mol. Med. 79 (10): 574–80. DOI:10.1007/s001090100257. PMID 11692154. 
  • Shiota D, Kasamatsu T, Dib SA, et al. (2002). „Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients with type 2 diabetes mellitus.”. Pancreas 24 (4): 386–90. DOI:10.1097/00006676-200205000-00010. PMID 11961492. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Runge S, Gram C, Brauner-Osborne H, et al. (2003). „Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus.”. J. Biol. Chem. 278 (30): 28005–10. DOI:10.1074/jbc.M301085200. PMID 12724331. 
  • Hassel S, Eichner A, Yakymovych M, et al. (2004). „Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry.”. Proteomics 4 (5): 1346–58. DOI:10.1002/pmic.200300770. PMID 15188402. 
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). „The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”. Genome Res. 14 (10B): 2121–7. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334. 
  • Mortensen OH, Dichmann DS, Abrahamsen N, et al. (2007). „Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.”. Gene 393 (1-2): 127–36. DOI:10.1016/j.gene.2007.01.023. PMID 17374560. 

Vidi još

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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)