Melatonin receptor 1A

MTNR1A

Identifiers

MTNR1A, MEL-1A-R, MT1, Melatonin receptor 1A

External IDs

MGI: 102967 HomoloGene: 21207 GeneCards: MTNR1A

Targeted by Drug

6-hydroxymelatonin, agomelatine, GR 196429, ly-156735, melatonin, ramelteon, tasimelteon, luzindole^[1]

Gene ontology
Molecular function	• hormone binding • G-protein coupled receptor activity • organic cyclic compound binding • signal transducer activity • melatonin receptor activity • protein binding
Cellular component	• integral component of membrane • membrane • receptor complex • integral component of plasma membrane • plasma membrane
Biological process	• G-protein coupled receptor signaling pathway • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger • positive regulation of cGMP biosynthetic process • mating behavior • cell surface receptor signaling pathway • signal transduction • circadian rhythm
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


4543


17773

Ensembl


ENSG00000168412


ENSMUSG00000054764

UniProt


P48039


Q61184

RefSeq (mRNA)


NM_005958


NM_008639

RefSeq (protein)


NP_005949.1


NP_032665.1

Location (UCSC)

Chr 4: 186.53 – 186.56 Mb

Chr 8: 45.07 – 45.09 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Melatonin receptor type 1A is a protein that in humans is encoded by the MTNR1A gene.^[4]^[5]

Function

This gene encodes the MT₁ protein, one of two high-affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G protein-coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive effects of melatonin.^[5]

Ligands

Melatonin – full agonist
Afobazole – agonist
Agomelatine – agonist

References

↑ "Drugs that physically interact with Melatonin receptor type 1A view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Slaugenhaupt SA, Roca AL, Liebert CB, Altherr MR, Gusella JF, Reppert SM (May 1995). "Mapping of the gene for the Mel1a-melatonin receptor to human chromosome 4 (MTNR1A) and mouse chromosome 8 (Mtnr1a)". Genomics. 27 (2): 355–7. doi:10.1006/geno.1995.1056. PMID 7558006.
1 2 "Entrez Gene: MTNR1A melatonin receptor 1A".

Brzezinski A (Jan 1997). "Melatonin in humans". The New England Journal of Medicine. 336 (3): 186–95. doi:10.1056/NEJM199701163360306. PMID 8988899.
Khan AU, Olson DL (Aug 1975). "Physical therapy and exercise-induced bronchospasm". Physical Therapy. 55 (8): 878–81. PMID 1144527.
Reppert SM, Weaver DR, Ebisawa T (Nov 1994). "Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses". Neuron. 13 (5): 1177–85. doi:10.1016/0896-6273(94)90055-8. PMID 7946354.
Witt-Enderby PA, Dubocovich ML (Jul 1996). "Characterization and regulation of the human ML1A melatonin receptor stably expressed in Chinese hamster ovary cells". Molecular Pharmacology. 50 (1): 166–74. PMID 8700109.
Witt-Enderby PA, Masana MI, Dubocovich ML (Jul 1998). "Physiological exposure to melatonin supersensitizes the cyclic adenosine 3',5'-monophosphate-dependent signal transduction cascade in Chinese hamster ovary cells expressing the human mt1 melatonin receptor". Endocrinology. 139 (7): 3064–71. doi:10.1210/en.139.7.3064. PMID 9645677.
Ebisawa T, Kajimura N, Uchiyama M, Katoh M, Sekimoto M, Watanabe T, Ozeki Y, Ikeda M, Jodoi T, Sugishita M, Iwase T, Kamei Y, Kim K, Shibui K, Kudo Y, Yamada N, Toyoshima R, Okawa M, Takahashi K, Yamauchi T (Sep 1999). "Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders". Biochemical and Biophysical Research Communications. 262 (3): 832–7. doi:10.1006/bbrc.1999.1308. PMID 10471411.
Brydon L, Roka F, Petit L, de Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, Jockers R (Dec 1999). "Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins". Molecular Endocrinology. 13 (12): 2025–38. doi:10.1210/me.13.12.2025. PMID 10598579.
Niles LP, Wang J, Shen L, Lobb DK, Younglai EV (Oct 1999). "Melatonin receptor mRNA expression in human granulosa cells". Molecular and Cellular Endocrinology. 156 (1-2): 107–10. doi:10.1016/S0303-7207(99)00135-5. PMID 10612428.
Song CK, Bartness TJ (Aug 2001). "CNS sympathetic outflow neurons to white fat that express MEL receptors may mediate seasonal adiposity". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 281 (2): R666–72. PMID 11448873.
Roy D, Angelini NL, Fujieda H, Brown GM, Belsham DD (Nov 2001). "Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin". Endocrinology. 142 (11): 4711–20. doi:10.1210/en.142.11.4711. PMID 11606436.
Savaskan E, Olivieri G, Meier F, Brydon L, Jockers R, Ravid R, Wirz-Justice A, Müller-Spahn F (Jan 2002). "Increased melatonin 1a-receptor immunoreactivity in the hippocampus of Alzheimer's disease patients". Journal of Pineal Research. 32 (1): 59–62. doi:10.1034/j.1600-079x.2002.00841.x. PMID 11841602.
Savaskan E, Wirz-Justice A, Olivieri G, Pache M, Kräuchi K, Brydon L, Jockers R, Müller-Spahn F, Meyer P (Apr 2002). "Distribution of melatonin MT1 receptor immunoreactivity in human retina". The Journal of Histochemistry and Cytochemistry. 50 (4): 519–26. doi:10.1177/002215540205000408. PMID 11897804.
Ayoub MA, Couturier C, Lucas-Meunier E, Angers S, Fossier P, Bouvier M, Jockers R (Jun 2002). "Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer". The Journal of Biological Chemistry. 277 (24): 21522–8. doi:10.1074/jbc.M200729200. PMID 11940583.
Yuan L, Collins AR, Dai J, Dubocovich ML, Hill SM (Jun 2002). "MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells". Molecular and Cellular Endocrinology. 192 (1-2): 147–56. doi:10.1016/S0303-7207(02)00029-1. PMID 12088876.
Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J (Jul 2003). "Functional activity of serotoninergic and melatoninergic systems expressed in the skin". Journal of Cellular Physiology. 196 (1): 144–53. doi:10.1002/jcp.10287. PMID 12767050.
Morcuende JA, Minhas R, Dolan L, Stevens J, Beck J, Wang K, Weinstein SL, Sheffield V (Sep 2003). "Allelic variants of human melatonin 1A receptor in patients with familial adolescent idiopathic scoliosis". Spine. 28 (17): 2025–8; discussion 2029. doi:10.1097/01.BRS.0000083235.74593.49. PMID 12973153.
Aust S, Thalhammer T, Humpeler S, Jäger W, Klimpfinger M, Tucek G, Obrist P, Marktl W, Penner E, Ekmekcioglu C (Jan 2004). "The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia". Journal of Pineal Research. 36 (1): 43–8. doi:10.1046/j.1600-079X.2003.00095.x. PMID 14675129.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	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)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

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

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Melatonin receptor modulators

MTR	Agonists: 2-Iodomelatonin 2-Phenylmelatonin 5-Methoxyluzindole 6-Chloromelatonin 6-Fluoromelatonin 6-Hydroxymelatonin 6-Methoxymelatonin 6,7-Dichloro-2-methylmelatonin 8-M-PDOT Agomelatine AMMTC GR-135,531 (of MT₃) GR-196,429 Melatonin N-Acetylserotonin (normelatonin) N-Acetyltryptamine N-Butanoylmelatonin N-Propionylmelatonin Piromelatine Ramelteon S-24268 S-25150 Tasimelteon TIK-301 (LY-156,735) Antagonists: 4-P-ADOT 4-P-PDOT Afobazole DH-97 Luzindole N-Acetyltryptamine (of MT₃) Prazosin (of MT₃) S-20928 S-22153 S-24601 S-25567 S-26131

See also: Adrenergics Dopaminergics Serotonergics Monoamine reuptake and release modulators Monoamine metabolism modulators Monoamine neurotoxins

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Melatonin receptor 1A

Function

Ligands

See also

References

Further reading