Melatoninski receptor 1B

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Melatoninski receptor 1B (MTNR1B) je protein koji je kod ljudi kodiran MTNR1B genom.[1][2]

Melatoninski receptor 1B
Identifikatori
SimboliMTNR1B; FGQTL2; MEL-1B-R; MT2
Vanjski IDOMIM600804 MGI2181726 HomoloGene4350 IUPHAR: MT2 GeneCards: MTNR1B Gene
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez4544244701
EnsemblENSG00000134640ENSMUSG00000050901
UniProtP49286Q3SXF8
RefSeq (mRNA)NM_005959.3NM_145712.2
RefSeq (protein)NP_005950.1NP_663758.2
Lokacija (UCSC)Chr 11:
92.7 - 92.72 Mb
Chr 9:
15.67 - 15.68 Mb
PubMed pretraga[1][2]

Funkcija

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MT2 protein je jedan od dve forme receptora sa visokim afinitetom za melatonin, primarni hormon epifize. On je integralni membranski protein koji je G protein spregnuti receptor, 7-transmembranski receptor. On je prisutan prvenstveno u retini i mozgu. Smatra se da on učestvuje u od svetla zavisnim funkcijama u retini i da posreduje neurobiološke efekte melatonina.[1]

Klinički značaj

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Nekoliko studija je identifikovalo da su mutacije MTNR1B receptora vezane za povišeni prosečne nivoe krvnog šećera, i za oko 20 procenata povišen rizik razvoja tip 2 dijabetesa.[3][4][5] MTNR1B iRNK je izražena u ljudskim Langerhansovim ostrvcima, i imunocitohemija potvrđuje da je prvenstveno lociran u beta ćelijama.[4]

MT2R ligandi

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Sledeći MT2R ligandi su selektivni u odnosu na MT1R:

  • Jedinjenje 3d: antagonist sa sub-nM afinitetom[6]
  • Jedinjenje 18f: antagonist i jedinjenje 18g parcijalni agonist: sub-nM afinitet, >100-puta selektivniji u odnosu na MT1[7]
  • Jedinjenje 14: antagonist[8]
  • Jedinjenje 13: agonist[9]

Reference

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  1. 1,0 1,1 „Entrez Gene: MTNR1B melatonin receptor 1B”. 
  2. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (September 1995). „Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor”. Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–8. DOI:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007. 
  3. „Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified”. ScienceDaily. 28. 06. 2008.. Pristupljeno 18. 01. 2009. ; „Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study”. ScienceDaily. 08. 12. 2008.. Pristupljeno 18. 01. 2009. ; „Is There A Relationship Between Sleep-wake Rhythm And Diabetes? A New Gene Variant Influences Fasting Glucose Levels Via The Melatonin Metabolism”. ScienceDaily. 16. 01. 2009.. Pristupljeno 18. 01. 2009. 
  4. 4,0 4,1 Prokopenko I, Langenberg C, Florez JC, et al. (January 2009). „Variants in MTNR1B influence fasting glucose levels”. Nat. Genet. 41 (1): 77–81. DOI:10.1038/ng.290. PMC 2682768. PMID 19060907. ; Lyssenko V, Nagorny CL, Erdos MR, et al. (January 2009). „Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion”. Nat. Genet. 41 (1): 82–8. DOI:10.1038/ng.288. PMID 19060908. ; Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, et al. (January 2009). „A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk”. Nat. Genet. 41 (1): 89–94. DOI:10.1038/ng.277. PMID 19060909. 
  5. Staiger H, Machicao F, Schäfer SA, et al. (2008). Maedler, Kathrin. ur. „Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function”. PLoS ONE 3 (12): e3962. DOI:10.1371/journal.pone.0003962. PMC 2597741. PMID 19088850. 
  6. Rivara S, Lodola A, Mor M, et al. (2007). „N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands”. J. Med. Chem. 50 (26): 6618–26. DOI:10.1021/jm700957j. PMID 18052314. 
  7. Bedini A, Spadoni G, Gatti G, et al. (2006). „Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands”. J. Med. Chem. 49 (25): 7393–403. DOI:10.1021/jm060850a. PMID 17149869. 
  8. Yous S, Durieux-Poissonnier S, Lipka-Belloli E, et al. (2003). „Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands”. Bioorg. Med. Chem. 11 (5): 753–9. DOI:10.1016/S0968-0896(02)00473-X. PMID 12538005. 
  9. Mattson RJ, Catt JD, Keavy D, et al. (2003). „Indanyl piperazines as melatonergic MT2 selective agents”. Bioorg. Med. Chem. Lett. 13 (6): 1199–202. DOI:10.1016/S0960-894X(03)00090-8. PMID 12643943. 

Literatura

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