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Showing toxin card for Melatonin (T3D2972)

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Version 1.0
Creation Date 2009-07-21 20:28:16
Update Date 2010-05-18 21:01:18
Accession Number T3D2972
Name Melatonin
Compound Type
  • Adjuvant, Immunologic
  • Anticonvulsant
  • Antioxidant
  • Central Nervous System Depressant
  • Drug
  • Free Radical Scavenger
Description A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the pineal gland. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of sleep, mood, and reproduction. Melatonin is also an effective antioxidant. [PubChem]
Synonyms
  1. 5-Methoxy-N-acetyltryptamine
  2. Circadin
  3. Melapure
  4. Melatol
  5. Melatonin
  6. Melatonine
  7. Melovine
  8. N-(2-(5-Methoxyindol-3-yl)ethyl)acetamide
  9. N-(2-(5-methoxy-1H-indol-3-yl)ethyl)acetamide
  10. N-(2-(5-methoxyindol-3-yl)ethyl)-Acetamide
  11. N-[2-(5-Methoxy-1H-indol-3-yl)-ethyl]-acetamide
  12. N-[2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide
  13. N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide
  14. N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide
  15. N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-Acetamide
  16. N-[2-(5-methoxyindol-3-yl)ethyl]-Acetamide
  17. N-acetyl-5-methoxy-tryptamine
  18. N-acetyl-5-methoxy-tryptamine Melatonine
  19. Posidorm
  20. Regulin
  21. SITS
  22. n-acetyl-5-methoxytryptamine
  23. {N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-} Acetamide
  24. {N-[2-(5-methoxyindol-3-yl)ethyl]-} Acetamide
Chemical IUPAC Name N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide
Chemical Formula C13H16N2O2
Chemical Structure Structure
CAS Registry Number 73-31-4
InChI Identifier 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)
InChI Key InChIKey=DRLFMBDRBRZALE-UHFFFAOYSA-N
PubChem Compound ID 896 Link Image
KEGG ID C01598 Link Image
UniProt ID Not Available
OMIM ID 303800 303900 600950 604348 Link Image
ChEBI ID 16796 Link Image
BioCyc ID N-ACETYL-5-METHOXY-TRYPTAMINE Link Image
SuperToxic ID Not Available
CTD ID Not Available
Stitch ID Melatonin Link Image
DrugBank ID DB01065 Link Image
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Melatonin Link Image
Monoisotopic Mass 232.121178
MOL File Show
PDB File Show
SDF File Show
SMILES COC1=CC=C2NC=C(CCNC(C)=O)C2=C1
Appearance Not Available
Melting Point 117 oC
Solubility Not Available
Predicted LogP 1.1476
Route of Exposure Not Available
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.
Metabolism Hepatic. Metabolized in the liver by hydroxylation to 6-hydroxymelatonin.
Toxicity Values LD50: 3200 mg/kg (Oral, Rat) (S405)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Not Available
Minimum Risk Level Not Available
Health Effects Tolerance can develop, in which the person needs larger doses to achieve the desired effect; this can lead to overdose and death. Accidents or injury can also occur due to the side effects of loss of coordination, slowed reaction time, sleepiness and impaired judgment. Drugs in this category have a high potential for physical and psychological dependence. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
Symptoms Loss of coordination, slowed reaction time, sleepiness and impaired judgment.
Treatment Not Available
General References
  • U857 - Reiter RJ, Acuna-Castroviejo D, Tan DX, Burkhardt S: Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann N Y Acad Sci. 2001 Jun;939:200-15. [PubMed Link Image]
  • U854 - Caniato R, Filippini R, Piovan A, Puricelli L, Borsarini A, Cappelletti EM: Melatonin in plants. Adv Exp Med Biol. 2003;527:593-7. [PubMed Link Image]
  • U858 - Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Ohtani-Kaneko R, Hara M, Suzuki T, Reiter RJ: Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem Mol Biol Int. 1995 Mar;35(3):627-34. [PubMed Link Image]
  • U855 - 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. [PubMed Link Image]
  • U856 - Hardeland R: Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005 Jul;27(2):119-30. [PubMed Link Image]
  • U853 - Drugs.com
Targets
  1. Melatonin receptor type 1A
  2. Estrogen receptor
  3. Apoptosis regulator Bcl-2
  4. Alpha-synuclein
  5. Caspase-3
  6. Cytochrome c
Target 1 [top]
Target 1 ID 1266
Target 1 Name Melatonin receptor type 1A
Target 1 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.
Target 1 Description 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
Target 1 Synonyms
  1. Mel1a melatonin receptor; Mel-1A-R
Target 1 Gene Name MTNR1A
Target 1 Protein Sequence >Melatonin receptor type 1A 
MQGNGSALPNASQPVLRGDGARPSWLASALACVLIFTIVVDILGNLLVILSVYRNKKLRN
AGNIFVVSLAVADLVVAIYPYPLVLMSIFNNGWNLGYLHCQVSGFLMGLSVIGSIFNITG
IAINRYCYICHSLKYDKLYSSKNSLCYVLLIWLLTLAAVLPNLRAGTLQYDPRIYSCTFA
QSVSSAYTIAVVVFHFLVPMIIVIFCYLRIWILVLQVRQRVKPDRKPKLKPQDFRNFVTM
FVVFVLFAICWAPLNFIGLAVASDPASMVPRIPEWLFVASYYMAYFNSCLNAIIYGLLNQ
NFRKEYRRIIVSLCTARVFFVDSSNDVADRVKWKPSPLMTNNNVVKVDSV
Target 1 Number of Residues 350
Target 1 Molecular Weight 39374.3
Target 1 Theoretical pI 9.75
Target 1 GO Classification
Function
melatonin receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in melatonin receptor activity
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 30-50
  • 64-84
  • 103-123
  • 143-163
  • 188-208
  • 241-261
  • 275-295
Target 1 Essentiality Non Essential
Target 1 Domain Function PF00001:7tm_1
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB ID P48039 Link Image
Target 1 Cellular Location Cell membrane
Target 1 Gene Sequence Not Available
Target 1 GenBank Gene ID Not Available
Target 1 GeneCard ID MTNR1A Link Image
Target 1 GenAtlas ID MTNR1A Link Image
Target 1 HGNC ID HGNC:7463 Link Image
Target 1 Chromosome Location Not Available
Target 1 Locus 4q35.1
Target 1 SNPs SNPJam Report Link Image
Target 1 Toxin References
  • U877 - Park YJ, Park JG, Hiyakawa N, Lee YD, Kim SJ, Takemura A: Diurnal and circadian regulation of a melatonin receptor, MT1, in the golden rabbitfish, Siganus guttatus. Gen Comp Endocrinol. 2007 Jan 15;150(2):253-62. Epub 2006 Oct 16. [PubMed Link Image]
  • U875 - Tomas-Zapico C, Antonio Boga J, Caballero B, Vega-Naredo I, Sierra V, Alvarez-Garcia O, Tolivia D, Josefa Rodriguez-Colunga M, Coto-Montes A: Coexpression of MT1 and RORalpha1 melatonin receptors in the Syrian hamster Harderian gland. J Pineal Res. 2005 Aug;39(1):21-6. [PubMed Link Image]
  • U874 - 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. [PubMed Link Image]
  • U876 - Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao A, Jockers R, Van Heerikhuize J, Swaab DF: Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol. 2006 Dec 20;499(6):897-910. [PubMed Link Image]
  • U878 - Weil ZM, Hotchkiss AK, Gatien ML, Pieke-Dahl S, Nelson RJ: Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating. Brain Res Bull. 2006 Feb 15;68(6):425-9. Epub 2005 Oct 12. [PubMed Link Image]
Target 1 General References 7946354; 10471411; 15489334
Target 2 [top]
Target 2 ID 5
Target 2 Name Estrogen receptor
Target 2 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.
Target 2 Description 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
Target 2 Synonyms
  1. ER; Estradiol receptor; ER-alpha; Nuclear receptor subfamily 3 group A member 1
Target 2 Gene Name ESR1
Target 2 Protein Sequence >Estrogen receptor 
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY
EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPF
LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAK
ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQAC
RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR
SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINW
AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEG
MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLD
KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLL
LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
Target 2 Number of Residues 595
Target 2 Molecular Weight 66215.4
Target 2 Theoretical pI 8.14
Target 2 GO Classification
Function
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 2 General Function Involved in estrogen receptor activity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non Essential
Target 2 Domain Function PF00104:Hormone_recep PF02159:Oest_recep PF00105:zf-C4
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB ID P03372 Link Image
Target 2 Cellular Location Nucleus
Target 2 Gene Sequence >63 bp 
ATGCGCTGCGTCGCCTCTAACCTCGGGCTGTGCTCTTTTTCCAGGTGGCCCGCCGGTTTC
TGA
Target 2 GenBank Gene ID Not Available
Target 2 GeneCard ID ESR1 Link Image
Target 2 GenAtlas ID ESR1 Link Image
Target 2 HGNC ID HGNC:3467 Link Image
Target 2 Chromosome Location Not Available
Target 2 Locus 6q25.1
Target 2 SNPs SNPJam Report Link Image
Target 2 Toxin References
  • U861 - Ishido M: Transient inhibition of synergistically insulin-like growth factor-1- and bisphenol A-induced poliferation of estrogen receptor alpha (ERalpha)-positive human breast cancer MCF-7 cells by melatonin. Environ Sci. 2004;11(3):163-70. [PubMed Link Image]
  • U860 - Stevens RG: Circadian disruption and breast cancer: from melatonin to clock genes. Epidemiology. 2005 Mar;16(2):254-8. [PubMed Link Image]
  • U863 - Martinez-Campa C, Alonso-Gonzalez C, Mediavilla MD, Cos S, Gonzalez A, Ramos S, Sanchez-Barcelo EJ: Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. J Pineal Res. 2006 May;40(4):291-6. [PubMed Link Image]
  • U862 - Cini G, Neri B, Pacini A, Cesati V, Sassoli C, Quattrone S, D'Apolito M, Fazio A, Scapagnini G, Provenzani A, Quattrone A: Antiproliferative activity of melatonin by transcriptional inhibition of cyclin D1 expression: a molecular basis for melatonin-induced oncostatic effects. J Pineal Res. 2005 Aug;39(1):12-20. [PubMed Link Image]
  • U859 - 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. [PubMed Link Image]
Target 2 General References 3754034; 3753802; 8600466; 14574404; 7476978; 10619354; 7916651; 7539106
Target 3 [top]
Target 3 ID 1281
Target 3 Name Apoptosis regulator Bcl-2
Target 3 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.
Target 3 Description 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)
Target 3 Synonyms Not Available
Target 3 Gene Name BCL2
Target 3 Protein Sequence >Apoptosis regulator Bcl-2 
MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPA
ASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLH
LTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY
LNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK
Target 3 Number of Residues 239
Target 3 Molecular Weight 26265.7
Target 3 Theoretical pI 7.32
Target 3 GO Classification
Function
Not Available
Process
regulation of biological process
regulation of physiological process
regulation of cellular physiological process
regulation of programmed cell death
regulation of apoptosis
Component
cell
membrane
Target 3 General Function Involved in BH3 domain binding
Target 3 Pathways REACT_578-Apoptosis;
Target 3 Reactions Not Available
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 212-233
Target 3 Essentiality Non Essential
Target 3 Domain Function PF00452:Bcl-2 PF02180:BH4
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB ID P10415 Link Image
Target 3 Cellular Location Mitochondrion outer membrane
Target 3 Gene Sequence >720 bp 
CTCTGGGAAATATGGCGCACGCTGGGAGAACAGGGTACGATAACCGGGAGATAGTGATGA
AGTACATCCATTATAAGCTGTCGCAGAGGGGCTACGAGTGGGATGCGGGAGATGTGGGCG
CCGCGCCCCCGGGGGCCGCCCCCGCGCCGGGCATCTTCTCCTCGCAGCCCGGGCACACGC
CCCATACAGCCGCATCCCGGGACCCGGTCGCCAGGACCTCGCCGCTGCAGACCCCGGCTG
CCCCCGGCGCCGCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCCACCTGACCC
TCCGCCAGGCCGGCGACGACTTCTCCCGCCGCTACCGCCGCGACTTCGCCGAGATGTCCA
GGCAGCTGCACCTGACGCCCTTCACCGCGCGGGGACGCTTTGCCACGGTGGTGGAGGAGC
TCTTCAGGGACGGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCA
TGTGTGTGGAGAGCGTCAACCGGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGA
TGACTGAGTACCTGAACCGGCACCTGCACACCTGGATCCAGGATAACGGAGGCTGGGATG
CCTTTGTGGAACTGTACGGCCCCAGCATGCGGCCTCTGTTTGATTTCTCCTGGCTGTCTC
TGAAGACTCTGCTCAGTTTGGCCCTGGTGGGAGCTTGCATCACCCTGGGTGCCTATCTGG
Target 3 GenBank Gene ID Not Available
Target 3 GeneCard ID BCL2 Link Image
Target 3 GenAtlas ID BCL2 Link Image
Target 3 HGNC ID HGNC:990 Link Image
Target 3 Chromosome Location Chromosome:18
Target 3 Locus 18q21.33|18q21.3
Target 3 SNPs SNPJam Report Link Image
Target 3 Toxin References
  • U867 - Yang QH, Xu JN, Xu RK, Pang SF: Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats. J Pineal Res. 2006 Apr;40(3):230-5. [PubMed Link Image]
  • U868 - Chetsawang B, Putthaprasart C, Phansuwan-Pujito P, Govitrapong P: Melatonin protects against hydrogen peroxide-induced cell death signaling in SH-SY5Y cultured cells: involvement of nuclear factor kappa B, Bax and Bcl-2. J Pineal Res. 2006 Sep;41(2):116-23. [PubMed Link Image]
  • U866 - 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. [PubMed Link Image]
  • U864 - 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. [PubMed Link Image]
  • U865 - Trubiani O, Recchioni R, Moroni F, Pizzicannella J, Caputi S, Di Primio R: Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation. J Pineal Res. 2005 Nov;39(4):425-31. [PubMed Link Image]
Target 3 General References 3523487; 1508712; 2875799; 2834197; 3285301; 15489334; 1339299; 2250705; 8183370
Target 4 [top]
Target 4 ID 41
Target 4 Name Alpha-synuclein
Target 4 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.
Target 4 Description May be involved in the regulation of dopamine release and transport. Soluble protein, normally localized primarily at the presynaptic region of axons, which can form filamentous aggregates that are the major non amyloid component of intracellular inclusions in several neurodegenerative diseases (synucleinopathies). Induces fibrillization of microtubule- associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation
Target 4 Synonyms
  1. Non-A beta component of AD amyloid; Non-A4 component of amyloid precursor; NACP
Target 4 Gene Name SNCA
Target 4 Protein Sequence >Alpha-synuclein 
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
DNEAYEMPSEEGYQDYEPEA
Target 4 Number of Residues 140
Target 4 Molecular Weight 14460.2
Target 4 Theoretical pI 4.37
Target 4 GO Classification
Function
Not Available
Process
Not Available
Component
cell
intracellular
cytoplasm
Target 4 General Function Involved in alpha-tubulin binding
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non Essential
Target 4 Domain Function PF01387:Synuclein
Target 4 GenBank ID Protein Not Available
Target 4 UniProtKB ID P37840 Link Image
Target 4 Cellular Location Cytoplasm. Membrane. Nucleus
Target 4 Gene Sequence >423 bp 
ATGGATGTATTCATGAAAGGACTTTCAAAGGCCAAGGAGGGAGTTGTGGCTGCTGCTGAG
AAAACCAAACAGGGTGTGGCAGAAGCAGCAGGAAAGACAAAAGAGGGTGTTCTCTATGTA
GGCTCCAAAACCAAGGAGGGAGTGGTGCATGGTGTGGCAACAGTGGCTGAGAAGACCAAA
GAGCAAGTGACAAATGTTGGAGGAGCAGTGGTGACGGGTGTGACAGCAGTAGCCCAGAAG
ACAGTGGAGGGAGCAGGGAGCATTGCAGCAGCCACTGGCTTTGTCAAAAAGGACCAGTTG
GGCAAGAATGAAGAAGGAGCCCCACAGGAAGGAATTCTGGAAGATATGCCTGTGGATCCT
GACAATGAGGCTTATGAAATGCCTTCTGAGGAAGGGTATCAAGACTACGAACCTGAAGCC
TAA
Target 4 GenBank Gene ID Not Available
Target 4 GeneCard ID SNCA Link Image
Target 4 GenAtlas ID SNCA Link Image
Target 4 HGNC ID HGNC:11138 Link Image
Target 4 Chromosome Location Not Available
Target 4 Locus 4q21
Target 4 SNPs SNPJam Report Link Image
Target 4 Toxin References
  • U870 - Lin AM, Fang SF, Chao PL, Yang CH: Melatonin attenuates arsenite-induced apoptosis in rat brain: involvement of mitochondrial and endoplasmic reticulum pathways and aggregation of alpha-synuclein. J Pineal Res. 2007 Sep;43(2):163-71. [PubMed Link Image]
  • U869 - Ishido M: Melatonin inhibits maneb-induced aggregation of alpha-synuclein in rat pheochromocytoma cells. J Pineal Res. 2007 Mar;42(2):125-30. [PubMed Link Image]
Target 4 General References 8248242; 7601450; 7802671; 11156617; 14702039
Target 5 [top]
Target 5 ID 1282
Target 5 Name Caspase-3
Target 5 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.
Target 5 Description 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
Target 5 Synonyms
  1. CASP-3; Apopain; Cysteine protease CPP32; CPP-32; Yama protein; SREBP cleavage activity 1; SCA-1; Caspase-3 subunit p17; Caspase-3 subunit p12
Target 5 Gene Name CASP3
Target 5 Protein Sequence >Caspase-3 
MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTG
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
Target 5 Number of Residues 277
Target 5 Molecular Weight 31607.6
Target 5 Theoretical pI 6.51
Target 5 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
cysteine-type endopeptidase activity
caspase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
Not Available
Target 5 General Function Involved in caspase activity
Target 5 Pathways REACT_578-Apoptosis;
Target 5 Reactions Not Available
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non Essential
Target 5 Domain Function PF00656:Peptidase_C14
Target 5 GenBank ID Protein Not Available
Target 5 UniProtKB ID P42574 Link Image
Target 5 Cellular Location Cytoplasm
Target 5 Gene Sequence >834 bp 
ATGGAGAACACTGAAAACTCAGTGGATTCAAAATCCATTAAAAATTTGGAACCAAAGATC
ATACATGGAAGCGAATCAATGGACTCTGGAATATCCCTGGACAACAGTTATAAAATGGAT
TATCCTGAGATGGGTTTATGTATAATAATTAATAATAAGAATTTTCATAAAAGCACTGGA
ATGACATCTCGGTCTGGTACAGATGTCGATGCAGCAAACCTCAGGGAAACATTCAGAAAC
TTGAAATATGAAGTCAGGAATAAAAATGATCTTACACGTGAAGAAATTGTGGAATTGATG
CGTGATGTTTCTAAAGAAGATCACAGCAAAAGGAGCAGTTTTGTTTGTGTGCTTCTGAGC
CATGGTGAAGAAGGAATAATTTTTGGAACAAATGGACCTGTTGACCTGAAAAAAATAACA
AACTTTTTCAGAGGGGATCGTTGTAGAAGTCTAACTGGAAAACCCAAACTTTTCATTATT
CAGGCCTGCCGTGGTACAGAACTGGACTGTGGCATTGAGACAGACAGTGGTGTTGATGAT
GACATGGCGTGTCATAAAATACCAGTGGATGCCGACTTCTTGTATGCATACTCCACAGCA
CCTGGTTATTATTCTTGGCGAAATTCAAAGGATGGCTCCTGGTTCATCCAGTCGCTTTGT
GCCATGCTGAAACAGTATGCCGACAAGCTTGAATTTATGCACATTCTTACCCGGGTTAAC
CGAAAGGTGGCAACAGAATTTGAGTCCTTTTCCTTTGACGCTACTTTTCATGCAAAGAAA
CAGATTCCATGTATTGTTTCCATGCTCACAAAAGAACTCTATTTTTATCACTAA
Target 5 GenBank Gene ID Not Available
Target 5 GeneCard ID CASP3 Link Image
Target 5 GenAtlas ID CASP3 Link Image
Target 5 HGNC ID HGNC:1504 Link Image
Target 5 Chromosome Location Not Available
Target 5 Locus 4q34
Target 5 SNPs SNPJam Report Link Image
Target 5 Toxin References
  • U873 - Feng Z, Zhang JT: Long-term melatonin or 17beta-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats. Free Radic Biol Med. 2005 Jul 15;39(2):195-204. Epub 2005 Mar 25. [PubMed Link Image]
  • U866 - 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. [PubMed Link Image]
  • U864 - 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. [PubMed Link Image]
  • U872 - Wenzel U, Nickel A, Daniel H: Melatonin potentiates flavone-induced apoptosis in human colon cancer cells by increasing the level of glycolytic end products. Int J Cancer. 2005 Aug 20;116(2):236-42. [PubMed Link Image]
  • U871 - Juknat AA, Mendez Mdel V, Quaglino A, Fameli CI, Mena M, Kotler ML: Melatonin prevents hydrogen peroxide-induced Bax expression in cultured rat astrocytes. J Pineal Res. 2005 Mar;38(2):84-92. [PubMed Link Image]
Target 5 General References 7983002; 7774019; 15003516; 15489334; 7596430; 8755496; 8696339; 10213689
Target 6 [top]
Target 6 ID 1283
Target 6 Name Cytochrome c
Target 6 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.
Target 6 Description 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
Target 6 Synonyms Not Available
Target 6 Gene Name CYCS
Target 6 Protein Sequence >Cytochrome c 
MGDVEKGKKIFIMKCSQCHTVEKGGKHKTGPNLHGLFGRKTGQAPGYSYTAANKNKGIIW
GEDTLMEYLENPKKYIPGTKMIFVGIKKKEERADLIAYLKKATNE
Target 6 Number of Residues 105
Target 6 Molecular Weight 11748.7
Target 6 Theoretical pI 10.16
Target 6 GO Classification
Function
transporter activity
electron transporter activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 6 General Function Energy production and conversion
Target 6 Pathways REACT_578-Apoptosis;
Target 6 Reactions Not Available
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • None
Target 6 Essentiality Non Essential
Target 6 Domain Function PF00034:Cytochrom_C
Target 6 GenBank ID Protein Not Available
Target 6 UniProtKB ID P99999 Link Image
Target 6 Cellular Location Mitochondrion matrix
Target 6 Gene Sequence Not Available
Target 6 GenBank Gene ID Not Available
Target 6 GeneCard ID CYCS Link Image
Target 6 GenAtlas ID CYCS Link Image
Target 6 HGNC ID HGNC:19986 Link Image
Target 6 Chromosome Location Not Available
Target 6 Locus 7p15.2
Target 6 SNPs SNPJam Report Link Image
Target 6 Toxin References
  • U870 - Lin AM, Fang SF, Chao PL, Yang CH: Melatonin attenuates arsenite-induced apoptosis in rat brain: involvement of mitochondrial and endoplasmic reticulum pathways and aggregation of alpha-synuclein. J Pineal Res. 2007 Sep;43(2):163-71. [PubMed Link Image]
  • U867 - Yang QH, Xu JN, Xu RK, Pang SF: Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats. J Pineal Res. 2006 Apr;40(3):230-5. [PubMed Link Image]
  • U879 - Semak I, Naumova M, Korik E, Terekhovich V, Wortsman J, Slominski A: A novel metabolic pathway of melatonin: oxidation by cytochrome C. Biochemistry. 2005 Jul 5;44(26):9300-7. [PubMed Link Image]
  • U866 - 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. [PubMed Link Image]
  • U880 - Han YX, Zhang SH, Wang XM, Wu JB: Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion. J Zhejiang Univ Sci B. 2006 Feb;7(2):142-7. [PubMed Link Image]
Target 6 General References 2849112; 17974005; 12853948; 12690205; 15489334; 13933734; 14063298; 9515723

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government.