T3DB Logo

Showing toxin card for Copper aspirinate (T3D1186)

Legend: toxin field target field

Version 1.0
Creation Date 2009-06-19 21:58:25
Update Date 2010-05-18 20:52:36
Accession Number T3D1186
Name Copper aspirinate
Compound Type
  • Aromatic Hydrocarbon
  • Copper Compound
  • Organic Compound
  • Organometallic
Description Copper aspirinate is an aspirin chelate of copper(II) cations (Cu2+). It is used to treat rheumatoid arthritis. Copper is a chemical element with the symbol Cu and atomic number 29. Copper is an essential elements in plants and animals as it is required for the normal functioning of more than 30 enzymes. It occurs naturally throughout the environment in rocks, soil, water, and air. (R513, R514, R531)
Synonyms
  1. Copper aspirinate
  2. Copper, tetrakis(mu-salicylato)di-, tetracetate
  3. Cupric aspirin complex
  4. Cupric aspirinate
  5. Tetrakis(mu-(2-acetoxybenzoato-O1:O1'))dicopper
  6. Tetrakis-mu-acetylsalicylato-dicopper(II)
Chemical IUPAC Name dicopper(2+) ion tetrakis(2-(acetyloxy)benzoate)
Chemical Formula C36H28Cu2O16
Chemical Structure Structure
CAS Registry Number 23642-01-5
InChI Identifier InChI=1S/4C9H8O4.2Cu/c4*1-6(10)13-8-5-3-2-4-7(8)9(11)12;;/h4*2-5H,1H3,(H,11,12);;/q;;;;2*+2/p-4
InChI Key InChIKey=BXBJCCCIFADZBU-UHFFFAOYSA-J
PubChem Compound ID 92244 Link Image
KEGG ID Not Available
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID Not Available
BioCyc ID Not Available
SuperToxic ID Not Available
CTD ID C027058 Link Image
Stitch ID Copper aspirinate Link Image
DrugBank ID Not Available
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link Not Available
Monoisotopic Mass 841.996937
MOL File Show
PDB File Show
SDF File Show
SMILES [Cu++].[Cu++].CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O
Appearance Not Available
Melting Point Not Available
Solubility Not Available
Predicted LogP 1.2381
Route of Exposure Oral (R513) ; inhalation (R513) ; dermal (R513)
Mechanism of Action Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. Copper-induced emesis results from stimulation of the vagus nerve. (R513, R523, R525, R526)
Metabolism Copper is mainly absorbed through the gastrointestinal tract, but it can also be inhalated and absorbed dermally. It passes through the basolateral membrane, possibly via regulatory copper transporters, and is transported to the liver and kidney bound to serum albumin. The liver is the critical organ for copper homoeostasis. In the liver and other tissues, copper is stored bound to metallothionein, amino acids, and in association with copper-dependent enzymes, then partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes. Copper may induce the production of metallothionein and ceruloplasmin. The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase) transports copper ions into and out of cells. Physiologically normal levels of copper in the body are held constant by alterations in the rate and amount of copper absorption, compartmental distribution, and excretion. (R513, R520)
Toxicity Values Not Available
Lethal Dose 10 to 20 grams for an adult human (copper salts). (R273)
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Copper aspirinate is used to treat rheumatoid arthritis. (R531)
Minimum Risk Level Acute Oral: 0.01 mg/kg/day (R260) Intermediate Oral: 0.01 mg/kg/day (R260)
Health Effects People must absorb small amounts of copper every day because copper is essential for good health, however, high levels of copper can be harmful. Very-high doses of copper can cause damage to your liver and kidneys, and can even cause death. Copper may induce allergic responses in sensitive individuals. (R514, R520)
Symptoms Breathing high levels of copper can cause irritation of the nose and throat. Ingesting high levels of copper can cause nausea, vomiting, diarrhea, headache, dizziness, and respiratory difficulty. (R514, R520)
Treatment Not Available
General References
  • R523 - Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  • R526 - US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene.
  • R528 - Bardsley PA, Howard P, DeBacker W, Vermeire P, Mairesse M, Ledent C, Radermecker M, Bury T, Ansquer J: Two years treatment with almitrine bismesylate in patients with hypoxic chronic obstructive airways disease. Eur Respir J. 1991 Mar;4(3):308-10. [PubMed Link Image]
  • R514 - ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for copper. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA).
  • R525 - Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [PubMed Link Image]
  • R520 - International Programme on Chemical Safety (IPCS) INCHEM (1998). Environmental Health Criteria for Copper.
  • R513 - Wikipedia. Copper. Last Updated 29 May 2009.
  • R260 - ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA).
  • R273 - Baselt RC (2000). Disposition of Toxic Drugs and Chemicals in Man, 5th ed. Foster City, CA: Chemical Toxicology Institute.
  • R531 - Wikipedia. Copper aspirinate. Last Updated 23 January 2009.
Targets
  1. Alpha-synuclein
  2. Amyloid beta A4 protein
  3. Glucose-6-phosphate 1-dehydrogenase
  4. Glutathione reductase, mitochondrial
  5. Serum paraoxonase/arylesterase 1
  6. Serum paraoxonase/lactonase 3
Target 1 [top]
Target 1 ID 41
Target 1 Name Alpha-synuclein
Target 1 Mechanism of Action Copper binds to alpha-synuclein, initiating protein aggregation and likely contributing to the development of the neurodegenerative disorders Parkinson's disease and Alzheimer's disease. (R524)
Target 1 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 1 Synonyms
  1. Non-A beta component of AD amyloid; Non-A4 component of amyloid precursor; NACP
Target 1 Gene Name SNCA
Target 1 Protein Sequence >Alpha-synuclein 
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP
DNEAYEMPSEEGYQDYEPEA
Target 1 Number of Residues 140
Target 1 Molecular Weight 14460.2
Target 1 Theoretical pI 4.37
Target 1 GO Classification
Function
Not Available
Process
Not Available
Component
cell
intracellular
cytoplasm
Target 1 General Function Involved in alpha-tubulin binding
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non Essential
Target 1 Domain Function PF01387:Synuclein
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB ID P37840 Link Image
Target 1 Cellular Location Cytoplasm. Membrane. Nucleus
Target 1 Gene Sequence >423 bp 
ATGGATGTATTCATGAAAGGACTTTCAAAGGCCAAGGAGGGAGTTGTGGCTGCTGCTGAG
AAAACCAAACAGGGTGTGGCAGAAGCAGCAGGAAAGACAAAAGAGGGTGTTCTCTATGTA
GGCTCCAAAACCAAGGAGGGAGTGGTGCATGGTGTGGCAACAGTGGCTGAGAAGACCAAA
GAGCAAGTGACAAATGTTGGAGGAGCAGTGGTGACGGGTGTGACAGCAGTAGCCCAGAAG
ACAGTGGAGGGAGCAGGGAGCATTGCAGCAGCCACTGGCTTTGTCAAAAAGGACCAGTTG
GGCAAGAATGAAGAAGGAGCCCCACAGGAAGGAATTCTGGAAGATATGCCTGTGGATCCT
GACAATGAGGCTTATGAAATGCCTTCTGAGGAAGGGTATCAAGACTACGAACCTGAAGCC
TAA
Target 1 GenBank Gene ID Not Available
Target 1 GeneCard ID SNCA Link Image
Target 1 GenAtlas ID SNCA Link Image
Target 1 HGNC ID HGNC:11138 Link Image
Target 1 Chromosome Location Not Available
Target 1 Locus 4q21
Target 1 SNPs SNPJam Report Link Image
Target 1 Toxin References
  • R524 - Davies P, Fontaine SN, Moualla D, Wang X, Wright JA, Brown DR: Amyloidogenic metal-binding proteins: new investigative pathways. Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303. [PubMed Link Image]
Target 1 General References 8248242; 7601450; 7802671; 11156617; 14702039
Target 2 [top]
Target 2 ID 646
Target 2 Name Amyloid beta A4 protein
Target 2 Mechanism of Action Copper binds the N-terminal region of amyloid precursor protein, promoting the generation of _-amyloid from the protein. This is believed to contribute to the development of the neurodegenerative disorders Parkinson's disease and Alzheimer's disease. (R524)
Target 2 Description N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6)
Target 2 Synonyms
  1. Alzheimer disease amyloid protein; ABPP; APPI; APP; PreA4; Cerebral vascular amyloid peptide; CVAP; Protease nexin-II; PN-II; N-APP; Soluble APP-alpha; S-APP-alpha; Soluble APP-beta; S-APP-beta; C99; Beta-amyloid protein 42; Beta-APP42; Beta-amyloid protein 40; Beta-APP40; C83; P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59; Gamma-CTF(59); Amyloid intracellular domain 59; AICD-59; AID(59); Gamma-secretase C-terminal fragment 57; Gamma-CTF(57); Amyloid intracellular domain 57; AICD-57; AID(57); Gamma-secretase C-terminal fragment 50; Gamma-CTF(50); Amyloid intracellular domain 50; AICD-50; AID(50); C31
Target 2 Gene Name APP
Target 2 Protein Sequence >Amyloid beta A4 protein 
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Target 2 Number of Residues 770
Target 2 Molecular Weight 86942.7
Target 2 Theoretical pI 4.45
Target 2 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
binding
Process
Not Available
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in acetylcholine receptor binding
Target 2 Pathways REACT_604-Hemostasis;
Target 2 Reactions Not Available
Target 2 Signals
  • 1-17
Target 2 Transmembrane Regions
  • 700-723
Target 2 Essentiality Non Essential
Target 2 Domain Function PF02177:A4_EXTRA PF10515:APP_amyloid PF03494:Beta-APP PF00014:Kunitz_BPTI
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB ID P05067 Link Image
Target 2 Cellular Location Membrane
Target 2 Gene Sequence >2088 bp 
ATGCTGCCCGGTTTGGCACTGCTCCTGCTGGCCGCCTGGACGGCTCGGGCGCTGGAGGTA
CCCACTGATGGTAATGCTGGCCTGCTGGCTGAACCCCAGATTGCCATGTTCTGTGGCAGA
CTGAACATGCACATGAATGTCCAGAATGGGAAGTGGGATTCAGATCCATCAGGGACCAAA
ACCTGCATTGATACCAAGGAAGGCATCCTGCAGTATTGCCAAGAAGTCTACCCTGAACTG
CAGATCACCAATGTGGTAGAAGCCAACCAACCAGTGACCATCCAGAACTGGTGCAAGCGG
GGCCGCAAGCAGTGCAAGACCCATCCCCACTTTGTGATTCCCTACCGCTGCTTAGTTGGT
GAGTTTGTAAGTGATGCCCTTCTCGTTCCTGACAAGTGCAAATTCTTACACCAGGAGAGG
ATGGATGTTTGCGAAACTCATCTTCACTGGCACACCGTCGCCAAAGAGACATGCAGTGAG
AAGAGTACCAACTTGCATGACTACGGCATGTTGCTGCCCTGCGGAATTGACAAGTTCCGA
GGGGTAGAGTTTGTGTGTTGCCCACTGGCTGAAGAAAGTGACAATGTGGATTCTGCTGAT
GCGGAGGAGGATGACTCGGATGTCTGGTGGGGCGGAGCAGACACAGACTATGCAGATGGG
AGTGAAGACAAAGTAGTAGAAGTAGCAGAGGAGGAAGAAGTGGCTGAGGTGGAAGAAGAA
GAAGCCGATGATGACGAGGACGATGAGGATGGTGATGAGGTAGAGGAAGAGGCTGAGGAA
CCCTACGAAGAAGCCACAGAGAGAACCACCAGCATTGCCACCACCACCACCACCACCACA
GAGTCTGTGGAAGAGGTGGTTCGAGTTCCTACAACAGCAGCCAGTACCCCTGATGCCGTT
GACAAGTATCTCGAGACACCTGGGGATGAGAATGAACATGCCCATTTCCAGAAAGCCAAA
GAGAGGCTTGAGGCCAAGCACCGAGAGAGAATGTCCCAGGTCATGAGAGAATGGGAAGAG
GCAGAACGTCAAGCAAAGAACTTGCCTAAAGCTGATAAGAAGGCAGTTATCCAGCATTTC
CAGGAGAAAGTGGAATCTTTGGAACAGGAAGCAGCCAACGAGAGACAGCAGCTGGTGGAG
ACACACATGGCCAGAGTGGAAGCCATGCTCAATGACCGCCGCCGCCTGGCCCTGGAGAAC
TACATCACCGCTCTGCAGGCTGTTCCTCCTCGGCCTCGTCACGTGTTCAATATGCTAAAG
AAGTATGTCCGCGCAGAACAGAAGGACAGACAGCACACCCTAAAGCATTTCGAGCATGTG
CGCATGGTGGATCCCAAGAAAGCCGCTCAGATCCGGTCCCAGGTTATGACACACCTCCGT
GTGATTTATGAGCGCATGAATCAGTCTCTCTCCCTGCTCTACAACGTGCCTGCAGTGGCC
GAGGAGATTCAGGATGAAGTTGATGAGCTGCTTCAGAAAGAGCAAAACTATTCAGATGAC
GTCTTGGCCAACATGATTAGTGAACCAAGGATCAGTTACGGAAACGATGCTCTCATGCCA
TCTTTGACCGAAACGAAAACCACCGTGGAGCTCCTTCCCGTGAATGGAGAGTTCAGCCTG
GACGATCTCCAGCCGTGGCATTCTTTTGGGGCTGACTCTGTGCCAGCCAACACAGAAAAC
GAAGTTGAGCCTGTTGATGCCCGCCCTGCTGCCGACCGAGGACTGACCACTCGACCAGGT
TCTGGGTTGACAAATATCAAGACGGAGGAGATCTCTGAAGTGAAGATGGATGCAGAATTC
CGACATGACTCAGGATATGAAGTTCATCATCAAAAATTGGTGTTCTTTGCAGAAGATGTG
GGTTCAAACAAAGGTGCAATCATTGGACTCATGGTGGGCGGTGTTGTCATAGCGACAGTG
ATCGTCATCACCTTGGTGATGCTGAAGAAGAAACAGTACACATCCATTCATCATGGTGTG
GTGGAGGTTGACGCCGCTGTCACCCCAGAGGAGCGCCACCTGTCCAAGATGCAGCAGAAC
GGCTACGAAAATCCAACCTACAAGTTCTTTGAGCAGATGCAGAACTAG
Target 2 GenBank Gene ID Not Available
Target 2 GeneCard ID APP Link Image
Target 2 GenAtlas ID APP Link Image
Target 2 HGNC ID HGNC:620 Link Image
Target 2 Chromosome Location Chromosome:21
Target 2 Locus 21q21.2|21q21.3
Target 2 SNPs SNPJam Report Link Image
Target 2 Toxin References
  • R524 - Davies P, Fontaine SN, Moualla D, Wang X, Wright JA, Brown DR: Amyloidogenic metal-binding proteins: new investigative pathways. Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303. [PubMed Link Image]
Target 2 General References 2881207; 2893289; 2783775; 2110105; 1908403; 1587857; 9108164; 12859342
Target 3 [top]
Target 3 ID 650
Target 3 Name Glucose-6-phosphate 1-dehydrogenase
Target 3 Mechanism of Action Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)
Target 3 Description Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power
Target 3 Synonyms
  1. G6PD
Target 3 Gene Name G6PD
Target 3 Protein Sequence >Glucose-6-phosphate 1-dehydrogenase 
MAEQVALSRTQVCGILREELFQGDAFHQSDTHIFIIMGASGDLAKKKIYPTIWWLFRDGL
LPENTFIVGYARSRLTVADIRKQSEPFFKATPEEKLKLEDFFARNSYVAGQYDDAASYQR
LNSHMNALHLGSQANRLFYLALPPTVYEAVTKNIHESCMSQIGWNRIIVEKPFGRDLQSS
DRLSNHISSLFREDQIYRIDHYLGKEMVQNLMVLRFANRIFGPIWNRDNIACVILTFKEP
FGTEGRGGYFDEFGIIRDVMQNHLLQMLCLVAMEKPASTNSDDVRDEKVKVLKCISEVQA
NNVVLGQYVGNPDGEGEATKGYLDDPTVPRGSTTATFAAVVLYVENERWDGVPFILRCGK
ALNERKAEVRLQFHDVAGDIFHQQCKRNELVIRVQPNEAVYTKMMTKKPGMFFNPEESEL
DLTYGNRYKNVKLPDAYERLILDVFCGSQMHFVRSDELREAWRIFTPLLHQIELEKPKPI
PYIYGSRGPTEADELMKRVGFQYEGTYKWVNPHKL
Target 3 Number of Residues 515
Target 3 Molecular Weight 59256.3
Target 3 Theoretical pI 6.84
Target 3 GO Classification
Function
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
glucose-6-phosphate 1-dehydrogenase activity
Process
physiological process
metabolism
cellular metabolism
alcohol metabolism
monosaccharide metabolism
hexose metabolism
glucose metabolism
Component
Not Available
Target 3 General Function Carbohydrate transport and metabolism
Target 3 Pathways Carbohydrate degradation; pentose phosphate pathway; D- ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage):step 1/3
Target 3 Reactions Not Available
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non Essential
Target 3 Domain Function PF02781:G6PD_C PF00479:G6PD_N
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB ID P11413 Link Image
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >1548 bp 
ATGGCAGAGCAGGTGGCCCTGAGCCGGACCCACGTGTGCGGGATCCTGCGGGAAGAGCTT
TTCCAGGGCGATGCCTTCCATCAGTCGGATACACACATATTCATCATCATGGGTGCATCG
GGTGACCTGGCCAAGAAGAAGATCTACCCCACCATCTGGTGGCTGTTCCGGGATGGCCTT
CTGCCCGAAAACACCTTCATCGTGGGCTATGCCCGTTCCCGCCTCACAGTGGCTGACATC
CGCAAACAGAGTGAGCCCTTCTTCAAGGCCACCCCAGAGGAGAAGCTCAAGCTGGAGGAC
TTCTTTGCCCGCAACTCCTATGTGGCTGGCCAGTACGATGATGCAGCCTCCTACCAGCGC
CTCAACAGCCACATGAATGCCCTCCACCTGGGGTCACAGGCCAACCGCCTCTTCTACCTG
GCCTTGCCCCCGACCGTCTACGAGGCCGTCACCAAGAACATTCACGAGTCCTGCATGAGC
CAGATAGGCTGGAACCGCATCATCGTGGAGAAGCCCTTCGGGAGGGACCTGCAGAGCTCT
GACCGGCTGTCCAACCACATCTCCTCCCTGTTCCGTGAGGACCAGATCTACCGCATCGAC
CACTACCTGGGCAAGGAGATGGTGCAGAACCTCATGGTGCTGAGATTTGCCAACAGGATC
TTCGGCCCCATCTGGAACCGGGACAACATCGCCTGCGTTATCCTCACCTTCAAGGAGCCC
TTTGGCACTGAGGGTCGCGGGGGCTATTTCGATGAATTTGGGATCATCCGGGACGTGATG
CAGAACCACCTACTGCAGATGCTGTGTCTGGTGGCCATGGAGAAGCCCGCCTCCACCAAC
TCAGATGACGTCCGTGATGAGAAGGTCAAGGTGTTGAAATGCATCTCAGAGGTGCAGGCC
AACAATGTGGTCCTGGGCCAGTACGTGGGGAACCCCGATGGAGAGGGCGAGGCCACCAAA
GGGTACCTGGACGACCCCACGGTGCCCCGCGGGTCCACCACCGCCACTTTTGCAGCCGTC
GTCCTCTATGTGGAGAATGAGAGGTGGGATGGGGTGCCCTTCATCCTGCGCTGCGGCAAG
GCCCTGAACGAGCGCAAGGCCGAGGTGAGGCTGCAGTTCCATGATGTGGCCGGCGACATC
TTCCACCAGCAGTGCAAGCGCAACGAGCTGGTGATCCGCGTGCAGCCCAACGAGGCCGTG
TACACCAAGATGATGACCAAGAAGCCGGGCATGTTCTTCAACCCCGAGGAGTCGGAGCTG
GACCTGACCTACGGCAACAGATACAAGAACGTGAAGCTCCCTGACGCCTACGAGCGCCTC
ATCCTGGACGTCTTCTGCGGGAGCCAGATGCACTTCGTGCGCAGCGACGAGCTCCGTGAG
GCCTGGCGTATTTTCACCCCACTGCTGCACCAGATTGAGCTGGAGAAGCCCAAGCCCATC
CCCTATATTTATGGCAGCCGAGGCCCCACGGAGGCAGACGAGCTGATGAAGAGAGTGGGT
TTCCAGTATGAGGGCACCTACAAGTGGGTGAACCCCCACAAGCTCTGA
Target 3 GenBank Gene ID Not Available
Target 3 GeneCard ID G6PD Link Image
Target 3 GenAtlas ID G6PD Link Image
Target 3 HGNC ID HGNC:4057 Link Image
Target 3 Chromosome Location Not Available
Target 3 Locus Xq28
Target 3 SNPs SNPJam Report Link Image
Target 3 Toxin References
  • R523 - Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  • R525 - Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [PubMed Link Image]
  • R513 - Wikipedia. Copper. Last Updated 29 May 2009.
  • R526 - US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene.
Target 3 General References 3515319; 2428611; 1889820; 8733135; 15772651; 15489334; 2758468; 8466644; 1874446; 12665801
Target 4 [top]
Target 4 ID 7
Target 4 Name Glutathione reductase, mitochondrial
Target 4 Mechanism of Action Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)
Target 4 Description Maintains high levels of reduced glutathione in the cytosol
Target 4 Synonyms
  1. GRase; GR
Target 4 Gene Name GSR
Target 4 Protein Sequence >Glutathione reductase, mitochondrial 
MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAMACRQEPQPQGPPPAAG
AVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTCVNVGCVPKKVMWNTAVHS
EFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQNNLTKSHIEIIRGHAAFTSDP
KPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLGITSDGFFQLEELPGRSVIVGAG
YIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMISTNCTEELENAGVEVLKFSQVKEVKK
TLSGLEVSMVTAVPGRLPVMTMIPDVDCLLWAIGRVPNTKDLSLNKLGIQTDDKGHIIVD
EFQNTNVKGIYAVGDVCGKALLTPVAIAAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPP
IGTVGLTEDEAIHKYGIENVKTYSTSFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQ
GLGCDEMLQGFAVAVKMGATKADFDNTVAIHPTSSEELVTLR
Target 4 Number of Residues 522
Target 4 Molecular Weight 56256.6
Target 4 Theoretical pI 8.66
Target 4 GO Classification
Function
disulfide oxidoreductase activity
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
FAD binding
catalytic activity
oxidoreductase activity
transporter activity
electron transporter activity
glutathione-disulfide reductase activity
Process
generation of precursor metabolites and energy
electron transport
physiological process
metabolism
cellular metabolism
cofactor metabolism
coenzyme metabolism
glutathione metabolism
Component
cell
intracellular
cytoplasm
Target 4 General Function RNA processing and modification
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 PF00070:Pyr_redox PF07992:Pyr_redox_2 PF02852:Pyr_redox_dim
Target 4 GenBank ID Protein Not Available
Target 4 UniProtKB ID P00390 Link Image
Target 4 Cellular Location Mitochondrion. Cytoplasm
Target 4 Gene Sequence >1440 bp 
ATGGCCTGCAGGCAGGAGCCGCAGCCGCAGGGCCCGCCGCCCGCTGCTGGCGCCGTGGCC
TCCTATGACTACCTGGTGATCGGGGGCGGCTCGGGCGGGCTGGCCAGCGCGCGCAGGGCG
GCCGAGCTGGGTGCCAGGGCCGCCGTGGTGGAGAGCCACAAGCTGGGTGGCACTTGCGTG
AATGTTGGATGTGTACCCAAAAAGGTAATGTGGAACACAGCTGTCCACTCTGAATTCATG
CATGATCATGCTGATTATGGCTTTCCAAGTTGTGAGGGTAAATTCAATTGGCGTGTTATT
AAGGAAAAGCGGGATGCCTATGTGAGCCGCCTGAATGCCATCTATCAAAACAATCTCACC
AAGTCCCATATAGAAATCATCCGTGGCCATGCAGCCTTCACGAGTGATCCCAAGCCCACA
ATAGAGGTCAGTGGGAAAAAGTACACCGCCCCACACATCCTGATCGCCACAGGTGGTATG
CCCTCCACCCCTCATGAGAGCCAGATCCCCGGTGCCAGCTTAGGAATAACCAGCGATGGA
TTTTTTCAGCTGGAAGAATTGCCCGGCCGCAGCGTCATTGTTGGTGCAGGTTACATTGCT
GTGGAGATGGCAGGGATCCTGTCAGCCCTGGGTTCTAAGACATCACTGATGATACGGCAT
GATAAGGTACTTAGAAGTTTTGATTCAATGATCAGCACCAACTGCACGGAGGAGCTGGAG
AACGCTGGCGTGGAGGTGCTGAAGTTCTCCCAGGTCAAGGAGGTTAAAAAGACTTTGTCG
GGCTTGGAAGTCAGCATGGTTACTGCAGTTCCCGGTAGGCTACCAGTCATGACCATGATT
CCAGATGTTGACTGCCTGCTCTGGGCCATTGGGCGGGTCCCGAATACCAAGGACCTGAGT
TTAAACAAACTGGGGATTCAAACCGATGACAAGGGTCATATCATCGTAGACGAATTCCAG
AATACCAACGTCAAAGGCATCTATGCAGTTGGGGATGTATGTGGAAAAGCTCTTCTTACT
CCAGTTGCAATAGCTGCTGGCCGAAAACTTGCCCATCGACTTTTTGAATATAAGGAAGAT
TCCAAATTAGATTATAACAACATCCCAACTGTGGTCTTCAGCCACCCCCCTATTGGGACA
GTGGGACTCACGGAAGATGAAGCCATTCATAAATATGGAATAGAAAATGTGAAGACCTAT
TCAACGAGCTTTACCCCGATGTATCACGCAGTTACCAAAAGGAAAACAAAATGTGTGATG
AAAATGGTCTGTGCTAACAAGGAAGAAAAGGTGGTTGGGATCCATATGCAGGGACTTGGG
TGTGATGAAATGCTGCAGGGTTTTGCTGTTGCAGTGAAGATGGGAGCAACGAAGGCAGAC
TTTGACAACACAGTCGCCATTCACCCTACCTCTTCAGAAGAGCTGGTCACACTTCGTTGA
Target 4 GenBank Gene ID Not Available
Target 4 GeneCard ID GSR Link Image
Target 4 GenAtlas ID GSR Link Image
Target 4 HGNC ID HGNC:4623 Link Image
Target 4 Chromosome Location Not Available
Target 4 Locus 8p21.1
Target 4 SNPs SNPJam Report Link Image
Target 4 Toxin References
  • R523 - Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  • R525 - Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [PubMed Link Image]
  • R513 - Wikipedia. Copper. Last Updated 29 May 2009.
  • R526 - US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene.
Target 4 General References 2185014; 10708558; 16421571; 15489334; 7060551; 923580; 15592455; 7334521
Target 5 [top]
Target 5 ID 647
Target 5 Name Serum paraoxonase/arylesterase 1
Target 5 Mechanism of Action Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)
Target 5 Description Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. May mediate an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation
Target 5 Synonyms
  1. PON 1; Serum aryldialkylphosphatase 1; A-esterase 1; Aromatic esterase 1; K-45
Target 5 Gene Name PON1
Target 5 Protein Sequence >Serum paraoxonase/arylesterase 1 
MAKLIALTLLGMGLALFRNHQSSYQTRLNALREVQPVELPNCNLVKGIETGSEDMEILPN
GLAFISSGLKYPGIKSFNPNSPGKILLMDLNEEDPTVLELGITGSKFDVSSFNPHGISTF
TDEDNAMYLLVVNHPDAKSTVELFKFQEEEKSLLHLKTIRHKLLPNLNDIVAVGPEHFYG
TNDHYFLDPYLQSWEMYLGLAWSYVVYYSPSEVRVVAEGFDFANGINISPDGKYVYIAEL
LAHKIHVYEKHANWTLTPLKSLDFNTLVDNISVDPETGDLWVGCHPNGMKIFFYDSENPP
ASEVLRIQNILTEEPKVTQVYAENGTVLQGSTVASVYKGKLLIGTVFHKALYCEL
Target 5 Number of Residues 355
Target 5 Molecular Weight 39749.0
Target 5 Theoretical pI 4.89
Target 5 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on ester bonds
carboxylic ester hydrolase activity
arylesterase activity
Process
Not Available
Component
extracellular region
Target 5 General Function Involved in aryldialkylphosphatase activity
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non Essential
Target 5 Domain Function PF01731:Arylesterase
Target 5 GenBank ID Protein Not Available
Target 5 UniProtKB ID P27169 Link Image
Target 5 Cellular Location Secreted, extracellular space
Target 5 Gene Sequence >1068 bp 
ATGGCGAAGCTGATTGCGCTCACCCTCTTGGGGATGGGACTGGCACTCTTCAGGAACCAC
CAGTCTTCTTACCAAACACGACTTAATGCTCTCCGAGAGGTACAACCCGTAGAACTTCCT
AACTGTAATTTAGTTAAAGGAATCGAAACTGGCTCTGAAGACATGGAGATACTGCCTAAT
GGACTGGCTTTCATTAGCTCTGGATTAAAGTATCCTGGAATAAAGAGCTTCAACCCCAAC
AGTCCTGGAAAAATACTTCTGATGGACCTGAATGAAGAAGATCCAACAGTGTTGGAATTG
GGGATCACTGGAAGTAAATTTGATGTATCTTCATTTAACCCTCATGGGATTAGCACATTC
ACAGATGAAGATAATGCCATGTACCTCCTGGTGGTGAACCATCCAGATGCCAAGTCCACA
GTGGAGTTGTTTAAATTTCAAGAAGAAGAAAAATCGCTTTTGCATCTAAAAACCATCAGA
CATAAACTTCTGCCTAATTTGAATGATATTGTTGCTGTGGGACCTGAGCACTTTTATGGC
ACAAATGATCACTATTTTCTTGACCCCTACTTACAATCCTGGGAGATGTATTTGGGTTTA
GCGTGGTCGTATGTTGTCTACTATAGTCCAAGTGAAGTTCGAGTGGTGGCAGAAGGATTT
GATTTTGCTAATGGAATCAACATTTCACCCGATGGCAAGTATGTCTATATAGCTGAGTTG
CTGGCTCATAAGATTCATGTGTATGAAAAGCATGCTAATTGGACTTTAACTCCATTGAAG
TCCCTTGACTTTAATACCCTCGTGGATAACATATCTGTGGATCCTGAGACAGGAGACCTT
TGGGTTGGATGCCATCCCAATGGCATGAAAATCTTCTTCTATGACTCAGAGAATCCTCCT
GCATCAGAGGTGCTTCGAATCCAGAACATTCTAACAGAAGAACCTAAAGTGACACAGGTT
TATGCAGAAAATGGCACAGTGTTGCAAGGCAGTACAGTTGCCTCTGTGTACAAAGGGAAA
CTGCTGATTGGCACAGTGTTTCACAAAGCTCTTTACTGTGAGCTCTAA
Target 5 GenBank Gene ID Not Available
Target 5 GeneCard ID PON1 Link Image
Target 5 GenAtlas ID PON1 Link Image
Target 5 HGNC ID HGNC:9204 Link Image
Target 5 Chromosome Location Not Available
Target 5 Locus 7q21.3
Target 5 SNPs SNPJam Report Link Image
Target 5 Toxin References
  • R523 - Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  • R525 - Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [PubMed Link Image]
  • R513 - Wikipedia. Copper. Last Updated 29 May 2009.
  • R526 - US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene.
Target 5 General References 1657140; 7916578; 8393742; 8393745; 8812495; 9261565; 14702039; 12853948; 12690205
Target 6 [top]
Target 6 ID 649
Target 6 Name Serum paraoxonase/lactonase 3
Target 6 Mechanism of Action Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)
Target 6 Description Has very limited arylesterase and no paraoxonase activities but rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents (By similarity)
Target 6 Synonyms Not Available
Target 6 Gene Name PON3
Target 6 Protein Sequence >Serum paraoxonase/lactonase 3 
MGKLVALVLLGVGLSLVGEMFLAFRERVNASREVEPVEPENCHLIEELESGSEDIDILPS
GLAFISSGLKYPGMPNFAPDEPGKIFLMDLNEQNPRAQALEISGGFDKELFNPHGISIFI
DKDNTVYLYVVNHPHMKSTVEIFKFEEQQRSLVYLKTIKHELLKSVNDIVVLGPEQFYAT
RDHYFTNSLLSFFEMILDLRWTYVLFYSPREVKVVAKGFCSANGITVSADQKYVYVADVA
AKNIHIMEKHDNWDLTQLKVIQLGTLVDNLTVDPATGDILAGCHPNPMKLLNYNPEDPPG
SEVLRIQNVLSEKPRVSTVYANNGSVLQGTSVASVYHGKILIGTVFHKTLYCEL
Target 6 Number of Residues 354
Target 6 Molecular Weight 39607.2
Target 6 Theoretical pI 5.10
Target 6 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on ester bonds
carboxylic ester hydrolase activity
arylesterase activity
Process
Not Available
Component
extracellular region
Target 6 General Function Involved in arylesterase activity
Target 6 Pathways Not Available
Target 6 Reactions Not Available
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • 5-24
Target 6 Essentiality Non Essential
Target 6 Domain Function PF01731:Arylesterase
Target 6 GenBank ID Protein Not Available
Target 6 UniProtKB ID Q15166 Link Image
Target 6 Cellular Location Secreted, extracellular space (By similarity)
Target 6 Gene Sequence Not Available
Target 6 GenBank Gene ID Not Available
Target 6 GeneCard ID PON3 Link Image
Target 6 GenAtlas ID PON3 Link Image
Target 6 HGNC ID HGNC:9206 Link Image
Target 6 Chromosome Location Not Available
Target 6 Locus 7q21.3
Target 6 SNPs SNPJam Report Link Image
Target 6 Toxin References
  • R523 - Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  • R525 - Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [PubMed Link Image]
  • R513 - Wikipedia. Copper. Last Updated 29 May 2009.
  • R526 - US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene.
Target 6 General References 12853948; 15489334; 8661009; 16335952

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.