Melatoninski receptor 1B

Melatoninski receptor 1B
Melatoninski receptor 1B
Identifikatori
Simboli	MTNR1B; FGQTL2; MEL-1B-R; MT2
Vanjski ID	OMIM: 600804 MGI: 2181726 HomoloGene: 4350 IUPHAR: MT2 GeneCards: MTNR1B Gene
Ontologija gena
Molekularna funkcija	• aktivnost prenosa signala; • receptorska aktivnost; • aktivnost G-protein spregnutog receptor; • aktivnost melatoninskog receptora;
Celularna komponenta	• ćelijska membrana; • integralno sa ćelijskom membranom;
Biološki proces	• G-proteinska signalizacija, spregnuta sa cikličnim nukleotidnim sekundarnim glasnikom; • sinaptička transmisija; • glukozna homeostaza; • regulacija sekrecije insulina;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	4544
Ensembl	ENSG00000134640
UniProt	P49286
RefSeq (mRNA)	NM_005959.3
RefSeq (protein)	NP_005950.1
Lokacija (UCSC)	Chr 11:; 92.7 - 92.72 Mb
PubMed pretraga	[1]

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

Funkcija

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

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

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

^ ^а ^б „Entrez Gene: MTNR1B melatonin receptor 1B”.
^ Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (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. PMC 41041  . PMID 7568007. doi:10.1073/pnas.92.19.8734.
^ „Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified”. ScienceDaily. 28. 06. 2008. Приступљено 18. 01. 2009. ; „Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study”. ScienceDaily. 08. 12. 2008. Приступљено 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. Приступљено 18. 01. 2009.
^ ^а ^б Prokopenko I; Langenberg C; Florez JC; et al. (2009). „Variants in MTNR1B influence fasting glucose levels”. Nat. Genet. 41 (1): 77—81. PMC 2682768  . PMID 19060907. doi:10.1038/ng.290. ; Lyssenko V; Nagorny CL; Erdos MR; et al. (2009). „Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion”. Nat. Genet. 41 (1): 82—8. PMID 19060908. doi:10.1038/ng.288. ; Bouatia-Naji N; Bonnefond A; Cavalcanti-Proença C; et al. (2009). „A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk”. Nat. Genet. 41 (1): 89—94. PMID 19060909. doi:10.1038/ng.277.
^ Staiger H, Machicao F, Schäfer SA; et al. (2008). Maedler, Kathrin, ур. „Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function”. PLoS ONE. 3 (12): e3962. PMC 2597741  . PMID 19088850. doi:10.1371/journal.pone.0003962.
^ 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. PMID 18052314. doi:10.1021/jm700957j.
^ 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. PMID 17149869. doi:10.1021/jm060850a.
^ 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. PMID 12538005. doi:10.1016/S0968-0896(02)00473-X.
^ Mattson RJ; Catt JD; Keavy D; et al. (2003). „Indanyl piperazines as melatonergic MT2 selective agents”. Bioorg. Med. Chem. Lett. 13 (6): 1199—202. PMID 12643943. doi:10.1016/S0960-894X(03)00090-8.

Literatura

Brzezinski A; Brzezinski, Amnon (1997). „Melatonin in humans”. N. Engl. J. Med. 336 (3): 186—95. PMID 8988899. doi:10.1056/NEJM199701163360306.
Reppert SM; Godson C; Mahle CD; et al. (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. PMC 41041  . PMID 7568007. doi:10.1073/pnas.92.19.8734.
Reppert SM; Weaver DR; Ebisawa T; et al. (1996). „Cloning of a melatonin-related receptor from human pituitary”. FEBS Lett. 386 (2–3): 219—24. PMID 8647286. doi:10.1016/0014-5793(96)00437-1.
Niles LP; Wang J; Shen L; et al. (2000). „Melatonin receptor mRNA expression in human granulosa cells”. Mol. Cell. Endocrinol. 156 (1–2): 107—10. PMID 10612428. doi:10.1016/S0303-7207(99)00135-5.
Ebisawa T; Uchiyama M; Kajimura N; et al. (2000). „Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls”. Neurosci. Lett. 280 (1): 29—32. PMID 10696804. doi:10.1016/S0304-3940(99)00981-7.
Roy D; Angelini NL; Fujieda H; et al. (2001). „Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin”. Endocrinology. 142 (11): 4711—20. PMID 11606436. doi:10.1210/en.142.11.4711.
Ayoub MA; Couturier C; Lucas-Meunier E; et al. (2002). „Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer”. J. Biol. Chem. 277 (24): 21522—8. PMID 11940583. doi:10.1074/jbc.M200729200.
Yuan L; Collins AR; Dai J; et al. (2003). „MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells”. Mol. Cell. Endocrinol. 192 (1–2): 147—56. PMID 12088876. doi:10.1016/S0303-7207(02)00029-1.
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. PMC 139241  . PMID 12477932. doi:10.1073/pnas.242603899.
Slominski A; Pisarchik A; Zbytek B; et al. (2003). „Functional activity of serotoninergic and melatoninergic systems expressed in the skin”. J. Cell. Physiol. 196 (1): 144—53. PMID 12767050. doi:10.1002/jcp.10287.
Ayoub MA, Levoye A, Delagrange P, Jockers R (2004). „Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers”. Mol. Pharmacol. 66 (2): 312—21. PMID 15266022. doi:10.1124/mol.104.000398.
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. PMC 528928  . PMID 15489334. doi:10.1101/gr.2596504.
Mazna P; Berka K; Jelinkova I; et al. (2005). „Ligand binding to the human MT2 melatonin receptor: the role of residues in transmembrane domains 3, 6, and 7”. Biochem. Biophys. Res. Commun. 332 (3): 726—34. PMID 15913560. doi:10.1016/j.bbrc.2005.05.017.
Ha E; Choe BK; Jung KH; et al. (2005). „Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population”. J. Pineal Res. 39 (2): 201—5. PMID 16098099. doi:10.1111/j.1600-079X.2005.00237.x.
Savaskan E; Jockers R; Ayoub M; et al. (2007). „The MT2 melatonin receptor subtype is present in human retina and decreases in Alzheimer's disease”. Current Alzheimer research. 4 (1): 47—51. PMID 17316165. doi:10.2174/156720507779939823.
Suzuki S; Masui Y; Ohnuki M; et al. (2007). „Induction of metallothionein synthesis by cilostazol in mice and in human cultured neuronal cell lines”. Biol. Pharm. Bull. 30 (4): 791—4. PMID 17409522. doi:10.1248/bpb.30.791.
Qiu XS; Tang NL; Yeung HY; et al. (2007). „Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis”. Spine. 32 (16): 1748—53. PMID 17632395. doi:10.1097/BRS.0b013e3180b9f0ff.

Spoljašnje veze

„Melatonin Receptors: MT₂”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 03. 03. 2016. г.

Vidi još

Melatoninski receptor

[entrez-1] а ^б „Entrez Gene: MTNR1B melatonin receptor 1B”.

[pmid7568007-2] Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (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. PMC 41041  . PMID 7568007. doi:10.1073/pnas.92.19.8734.

[SN-3] „Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified”. ScienceDaily. 28. 06. 2008. Приступљено 18. 01. 2009. ; „Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study”. ScienceDaily. 08. 12. 2008. Приступљено 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. Приступљено 18. 01. 2009.

[Nat_Genet_2009-4] а ^б Prokopenko I; Langenberg C; Florez JC; et al. (2009). „Variants in MTNR1B influence fasting glucose levels”. Nat. Genet. 41 (1): 77—81. PMC 2682768  . PMID 19060907. doi:10.1038/ng.290. ; Lyssenko V; Nagorny CL; Erdos MR; et al. (2009). „Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion”. Nat. Genet. 41 (1): 82—8. PMID 19060908. doi:10.1038/ng.288. ; Bouatia-Naji N; Bonnefond A; Cavalcanti-Proença C; et al. (2009). „A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk”. Nat. Genet. 41 (1): 89—94. PMID 19060909. doi:10.1038/ng.277.

[pmid19088850-5] Staiger H, Machicao F, Schäfer SA; et al. (2008). Maedler, Kathrin, ур. „Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function”. PLoS ONE. 3 (12): e3962. PMC 2597741  . PMID 19088850. doi:10.1371/journal.pone.0003962.

[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. PMID 18052314. doi:10.1021/jm700957j.

[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. PMID 17149869. doi:10.1021/jm060850a.

[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. PMID 12538005. doi:10.1016/S0968-0896(02)00473-X.

[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. PMID 12643943. doi:10.1016/S0960-894X(03)00090-8.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]