Melatonin
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Basic Info
| Common Name | Melatonin(F04778) |
| 2D Structure | |
| Description | Melatonin is a biogenic amine that is found in animals, plants and microbes. Aaron B. Lerner of Yale University is credited for naming the hormone and for defining its chemical structure in 1958. In mammals, melatonin is produced by the pineal gland. The pineal gland is small endocrine gland, about the size of a rice grain and shaped like a pine cone (hence the name), that is located in the center of the brain (rostro-dorsal to the superior colliculus) but outside the blood-brain barrier. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle. In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin is also implicated in the regulation of mood, learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant. Most of the actions of melatonin are mediated through the binding and activation of melatonin receptors. Individuals with autism spectrum disorders (ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis. Reduced melatonin production has also been proposed as a likely factor in the significantly higher cancer rates in night workers. |
| FRCD ID | F04778 |
| CAS Number | 73-31-4 |
| PubChem CID | 896 |
| Formula | C13H16N2O2 |
| IUPAC Name | N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide |
| InChI Key | DRLFMBDRBRZALE-UHFFFAOYSA-N |
| InChI | InChI=1S/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16) |
| Canonical SMILES | CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC |
| Isomeric SMILES | CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC |
| Wikipedia | Melatonin |
| Synonyms |
73-31-4
5-Methoxy-N-acetyltryptamine
Melatonin
Melatonine
N-Acetyl-5-methoxytryptamine
Circadin
N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide
N-(2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide
Melatol
Melatonex
|
| Classifies |
Animal Toxin
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Indoles and derivatives |
| Subclass | Indoles |
| Intermediate Tree Nodes | Not available |
| Direct Parent | 3-alkylindoles |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | 3-alkylindole - Anisole - Alkyl aryl ether - Substituted pyrrole - Benzenoid - Pyrrole - Heteroaromatic compound - Propargyl-type 1,3-dipolar organic compound - Ether - Carboximidic acid derivative - Carboximidic acid - Organic 1,3-dipolar compound - Azacycle - Organic oxygen compound - Hydrocarbon derivative - Organopnictogen compound - Organic nitrogen compound - Organooxygen compound - Organonitrogen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as 3-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 3-position. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 232.283 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 4 |
| Complexity | 270 |
| Monoisotopic Mass | 232.121 |
| Exact Mass | 232.121 |
| XLogP | 0.8 |
| Formal Charge | 0 |
| Heavy Atom Count | 17 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9928 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2- | 0.5536 |
| P-glycoprotein Substrate | Substrate | 0.6188 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9569 |
| Non-inhibitor | 0.6838 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.5420 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7178 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8231 |
| CYP450 2D6 Substrate | Substrate | 0.5062 |
| CYP450 3A4 Substrate | Substrate | 0.6505 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9304 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.8084 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7194 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.6803 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9631 |
| Non-inhibitor | 0.5124 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9498 |
| Fish Toxicity | Low FHMT | 0.8707 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.5060 |
| Honey Bee Toxicity | Low HBT | 0.5608 |
| Biodegradation | Not ready biodegradable | 0.8764 |
| Acute Oral Toxicity | III | 0.7793 |
| Carcinogenicity (Three-class) | Non-required | 0.6457 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.2699 | LogS |
| Caco-2 Permeability | 0.9226 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.8922 | LD50, mol/kg |
| Fish Toxicity | 1.7593 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.1453 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| The multiple protective roles and molecular mechanisms of melatonin and its precursor N-acetylserotonin, in targeting brain injury and liver damage and in maintaining bone health. | Free Radic Biol Med | 2018 Oct 10 | 30315933 |
| Comparative effect of melatonin and quercetin in counteracting LPS induced oxidative stress in bone marrow mononuclear cells and spleen of Funambulus pennanti. | Food Chem Toxicol | 2018 Oct | 29964085 |
| Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence. | Int J Mol Sci | 2018 May 22 | 29786658 |
| Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine. | Biol Reprod | 2018 Mar 1 | 29373650 |
| Anti-inflammatory effects of Melatonin: a mechanistic review. | Crit Rev Food Sci Nutr | 2018 Jun 14:1-62 | 29902071 |
| Delay of Postharvest Browning in Litchi Fruit by Melatonin via the Enhancing ofAntioxidative Processes and Oxidation Repair. | J Agric Food Chem | 2018 Jul 18 | 29953220 |
| Attenuating effect of melatonin on lipopolysaccharide-induced chicken small intestine inflammation. | Poult Sci | 2018 Jul 1 | 29596657 |
| Melatonin protects against defects induced by deoxynivalenol during mouse oocyte maturation. | J Pineal Res | 2018 Aug | 29453798 |
| Melatonin attenuates arsenic induced nephropathy via the regulation of oxidative stress and inflammatory signaling cascades in mice. | Food Chem Toxicol | 2018 Aug | 29763682 |
| Melatonin attenuates scopolamine-induced cognitive impairment via protectingagainst demyelination through BDNF-TrkB signaling in the mouse dentate gyrus. | Chem Biol Interact | 2018 Apr 1 | 29476728 |
| Safety assessment and toxicological profiling of a novel combinational sunprotective dermal formulation containing melatonin and pumpkin seed oil. | Regul Toxicol Pharmacol | 2017 Oct | 28694170 |
| Melatonin mitigates neomycin-induced hair cell injury in zebrafish. | Drug Chem Toxicol | 2017 Oct | 27855522 |
| Melatonin potentiates the antitumor effect of curcumin by inhibitingIKKβ/NF-κB/COX-2 signaling pathway. | Int J Oncol | 2017 Oct | 28849163 |
| Melatonin and resveratrol reverse the toxic effect of high boron (B) and modulate biochemical parameters in pepper plants (Capsicum annuum L.). | Plant Physiol Biochem | 2017 Mar | 28088019 |
| Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism andHyperthyroidism: The Relation to Zinc. | Biochem Genet | 2017 Jun | 28097455 |
| The benefit of a supplement with the antioxidant melatonin on redox status andmuscle damage in resistance-trained athletes. | Appl Physiol Nutr Metab | 2017 Jul | 28192673 |
| Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational studyassessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bonedensity, bone marker turnover and health related quality of life inpostmenopausal osteopenic women following a one-year double-blind RCT and onosteoblast-osteoclast co-cultures. | Aging (Albany NY) | 2017 Jan 26 | 28130552 |
| Melatonin and derived l-tryptophan metabolites produced during alcoholicfermentation by different wine yeast strains. | Food Chem | 2017 Feb 15 | 27664655 |
| Melatonin Natural Health Products and Supplements: Presence of Serotonin andSignificant Variability of Melatonin Content. | J Clin Sleep Med | 2017 Feb 15 | 27855744 |
| Melatonin treatment attenuates postharvest decay and maintains nutritionalquality of strawberry fruits (Fragaria×anannasa cv. Selva) by enhancing GABAshunt activity. | Food Chem | 2017 Apr 15 | 27979142 |
Targets
- General Function:
- Melatonin receptor activity
- Specific Function:
- High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.
- Gene Name:
- MTNR1B
- Uniprot ID:
- P49286
- Molecular Weight:
- 40187.895 Da
References
- Boutin JA, Audinot V, Ferry G, Delagrange P: Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005 Aug;26(8):412-9. [15992934 ]
- General Function:
- Organic cyclic compound binding
- Specific Function:
- High affinity receptor for melatonin. Likely to mediates the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.
- Gene Name:
- MTNR1A
- Uniprot ID:
- P48039
- Molecular Weight:
- 39374.315 Da
- Mechanism of Action:
- Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
References
- Schuster C, Williams LM, Morris A, Morgan PJ, Barrett P: The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway. J Neuroendocrinol. 2005 Mar;17(3):170-8. [15796769 ]
- General Function:
- Phospholipase a2 activator activity
- Specific Function:
- Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.
- Gene Name:
- CASP3
- Uniprot ID:
- P42574
- Molecular Weight:
- 31607.58 Da
- Mechanism of Action:
- Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
References
- Jang MH, Jung SB, Lee MH, Kim CJ, Oh YT, Kang I, Kim J, Kim EH: Melatonin attenuates amyloid beta25-35-induced apoptosis in mouse microglial BV2 cells. Neurosci Lett. 2005 May 20-27;380(1-2):26-31. Epub 2005 Jan 25. [15854745 ]
- General Function:
- Nadph dehydrogenase (quinone) activity
- Specific Function:
- The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
- Gene Name:
- NQO2
- Uniprot ID:
- P16083
- Molecular Weight:
- 25918.4 Da
References
- Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. doi: 10.1016/j.taap.2009.05.012. Epub 2009 May 19. [19463840 ]
- General Function:
- Virus receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
- Gene Name:
- HTR2A
- Uniprot ID:
- P28223
- Molecular Weight:
- 52602.58 Da
References
- Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL: Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences. J Pharmacol Exp Ther. 1996 Feb;276(2):720-7. [8632342 ]
- Gene Name:
- SNCA
- Uniprot ID:
- P37840
- Molecular Weight:
- 14460.155 Da
- Mechanism of Action:
- Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
References
- Ishido M: Melatonin inhibits maneb-induced aggregation of alpha-synuclein in rat pheochromocytoma cells. J Pineal Res. 2007 Mar;42(2):125-30. [17286743 ]
- Uniprot ID:
- P62158
References
- Radogna F, Paternoster L, De Nicola M, Cerella C, Ammendola S, Bedini A, Tarzia G, Aquilano K, Ciriolo M, Ghibelli L: Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):37-45. doi: 10.1016/j.taap.2009.05.012. Epub 2009 May 19. [19463840 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity).
- Gene Name:
- CALR
- Uniprot ID:
- P27797
- Molecular Weight:
- 48141.2 Da
References
- Hardeland R: Melatonin: signaling mechanisms of a pleiotropic agent. Biofactors. 2009 Mar-Apr;35(2):183-92. doi: 10.1002/biof.23. [19449447 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.
- Gene Name:
- ASMT
- Uniprot ID:
- P46597
- Molecular Weight:
- 38452.51 Da
References
- Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976;16:33-51. [180879 ]
- General Function:
- Peroxidase activity
- Specific Function:
- Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils. Shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv by inducing bacterial fragmentation and lysis.
- Gene Name:
- EPX
- Uniprot ID:
- P11678
- Molecular Weight:
- 81039.5 Da
References
- Lu T, Galijasevic S, Abdulhamid I, Abu-Soud HM: Analysis of the mechanism by which melatonin inhibits human eosinophil peroxidase. Br J Pharmacol. 2008 Jul;154(6):1308-17. doi: 10.1038/bjp.2008.173. Epub 2008 Jun 2. [18516076 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.
- Gene Name:
- MT3
- Uniprot ID:
- P25713
- Molecular Weight:
- 6926.855 Da
References
- Leclerc V, Ettaoussi M, Rami M, Farce A, Boutin JA, Delagrange P, Caignard DH, Renard P, Berthelot P, Yous S: Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3. Eur J Med Chem. 2011 May;46(5):1622-9. doi: 10.1016/j.ejmech.2011.02.010. Epub 2011 Feb 15. [21377769 ]
- General Function:
- Peroxidase activity
- Specific Function:
- Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
- Gene Name:
- MPO
- Uniprot ID:
- P05164
- Molecular Weight:
- 83867.71 Da
References
- Galijasevic S, Abdulhamid I, Abu-Soud HM: Melatonin is a potent inhibitor for myeloperoxidase. Biochemistry. 2008 Feb 26;47(8):2668-77. doi: 10.1021/bi702016q. Epub 2008 Feb 1. [18237195 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).
- Gene Name:
- BCL2
- Uniprot ID:
- P10415
- Molecular Weight:
- 26265.66 Da
- Mechanism of Action:
- Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
References
- Jang MH, Jung SB, Lee MH, Kim CJ, Oh YT, Kang I, Kim J, Kim EH: Melatonin attenuates amyloid beta25-35-induced apoptosis in mouse microglial BV2 cells. Neurosci Lett. 2005 May 20-27;380(1-2):26-31. Epub 2005 Jan 25. [15854745 ]
- General Function:
- Metal ion binding
- Specific Function:
- Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.
- Gene Name:
- CYCS
- Uniprot ID:
- P99999
- Molecular Weight:
- 11748.69 Da
- Mechanism of Action:
- Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
References
- Baydas G, Reiter RJ, Akbulut M, Tuzcu M, Tamer S: Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels. Neuroscience. 2005;135(3):879-86. [16213988 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
- Mechanism of Action:
- Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
References
- Cos S, Martinez-Campa C, Mediavilla MD, Sanchez-Barcelo EJ: Melatonin modulates aromatase activity in MCF-7 human breast cancer cells. J Pineal Res. 2005 Mar;38(2):136-42. [15683469 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
- Gene Name:
- HTR2B
- Uniprot ID:
- P41595
- Molecular Weight:
- 54297.41 Da
References
- Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL: Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences. J Pharmacol Exp Ther. 1996 Feb;276(2):720-7. [8632342 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
- Gene Name:
- HTR2C
- Uniprot ID:
- P28335
- Molecular Weight:
- 51820.705 Da
References
- Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL: Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences. J Pharmacol Exp Ther. 1996 Feb;276(2):720-7. [8632342 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity).Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).
- Gene Name:
- RORB
- Uniprot ID:
- Q92753
- Molecular Weight:
- 53219.385 Da
References
- Becker-Andre M, Wiesenberg I, Schaeren-Wiemers N, Andre E, Missbach M, Saurat JH, Carlberg C: Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J Biol Chem. 1994 Nov 18;269(46):28531-4. [7961794 ]