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Record Information
Version2.0
Creation Date2009-03-06 18:57:55 UTC
Update Date2014-12-24 20:20:53 UTC
Accession NumberT3D0017
Identification
Common NameDieldrin
ClassSmall Molecule
DescriptionDieldrin is a chlorinated hydrocarbon used as an insecticide, either by itself or as a component of the closely related insectide aldrin. As dieldrin is neurotoxin and tends to bioaccumulate, its use is now banned in most parts of the world. (5) Dieldrin is a chlorinated hydrocarbon originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the insect to form dieldrin which is the active compound. Both dieldrin and aldrin are named after the Diels-Alder reaction which is used to form aldrin from a mixture of norbornadiene and hexachlorocyclopentadiene.
Compound Type
  • Ether
  • Organic Compound
  • Organochloride
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(1Aalpha,2beta,2aalpha,3beta,6beta,6aalpha,7beta,7aalpha)-3,4,5,6,9,9-hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-2,7:3,6-dimethanonaphtho[2,3-b]oxirene
(1R,4S,4AS,5R,6R,7S,8S,8ar)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene
1,2,3,4,10,10-Hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-endo-exo-5,8-dimethanonaphthalene
Aldrin epoxide
Alvit
Alvit 55
Deildrin
Dieldren
Dieldrex
Dieldrine
Dieldrite
Dieldrix
Dielmoth
Dildrin
Dorytox
Exo-dieldrin
HEOD
Hexachloroepoxyoctahydro-endo,exo-dimethanonaphthalene
Illoxol
Insectlack
Kombi-albertan
Murdiel
Octalox
Oxralox
Panoram D-31
Quintox
Shelltox
Termitox
Termitoxrm
Chemical FormulaC12H8Cl6O
Average Molecular Mass380.909 g/mol
Monoisotopic Mass377.871 g/mol
CAS Registry Number60-57-1
IUPAC Name(1R,2S,3S,6R,7R,8S,9S,11R)-3,4,5,6,13,13-hexachloro-10-oxapentacyclo[6.3.1.1³,⁶.0²,⁷.0⁹,¹¹]tridec-4-ene
Traditional Namedieldrin
SMILES[H][C@]12O[C@@]1([H])[C@@]1([H])C[C@]2([H])[C@@]2([H])[C@]1([H])[C@@]1(Cl)C(Cl)=C(Cl)[C@]2(Cl)C1(Cl)Cl
InChI IdentifierInChI=1/C12H8Cl6O/c13-8-9(14)11(16)5-3-1-2(6-7(3)19-6)4(5)10(8,15)12(11,17)18/h2-7H,1H2/t2-,3+,4+,5-,6-,7+,10+,11-
InChI KeyInChIKey=DFBKLUNHFCTMDC-PICURKEMNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as monoterpenoids. Monoterpenoids are compounds containing a chain of two isoprene units.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassMonoterpenoids
Direct ParentMonoterpenoids
Alternative Parents
Substituents
  • Monoterpenoid
  • Norbornane monoterpenoid
  • Oxepane
  • Oxane
  • Dialkyl ether
  • Oxirane
  • Ether
  • Oxacycle
  • Vinyl chloride
  • Vinyl halide
  • Organoheterocyclic compound
  • Haloalkene
  • Chloroalkene
  • Organooxygen compound
  • Hydrocarbon derivative
  • Alkyl chloride
  • Alkyl halide
  • Organic oxygen compound
  • Organohalogen compound
  • Organochloride
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cell junction
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Lysosome
  • Membrane
  • Microsome
  • Mitochondrion
  • Nucleolus
  • Peroxisome
  • Plasma Membrane
  • Sarcoplasmic Reticulum
  • Synaptic Vesicle
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Base excision repairNot Availablemap03410
ProteasomeNot AvailableNot Available
Phenylalanine metabolismNot Availablemap00360
Oxidative phosphorylationNot Availablemap00190
Circadian rhythmNot Availablemap04710
Insulin secretionNot Availablemap04911
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point175.5°C
Boiling PointNot Available
Solubility0.000195 mg/mL at 25 °C [BIGGAR,JW & RIGGS,RI (1974)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0002 g/LALOGPS
logP4.98ALOGPS
logP3.95ChemAxon
logS-6.3ALOGPS
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.53 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity78.01 m³·mol⁻¹ChemAxon
Polarizability31.36 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0009000000-4e3ab80ba2cb5f78445d2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01t9-0009000000-47b57ee68ea2b95cb4a82016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-003r-9124000000-f5c8679adbd456c1b9e62016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0009000000-c15682ff19a328a64b012016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0009000000-41a18726a0ad03aeb1f32016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-2209000000-4c9e51dcaa850bbc46a82016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral (6) ; inhalation (6) ; dermal (6)
Mechanism of ToxicityDieldrin antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions. Dieldrin also inhibits Na+ K+ ATPase and Ca2+ and Mg2+ ATPase which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the CNS. This results in hyperexcitation and generalized seizures. Dieldrin also binds to alpha-synuclein, leading to the formation of intracellular fibrils. (3, 6)
MetabolismDieldrin is absorbed throught the gastrointestinal tract, lungs and skin. Following absorption, dieldrin is redistributed primarily to fat via the lymphatic system. Dieldrin is metabolized by liver microsomal monooxygenases and epoxide hydratases. Its metabolites, of which the primary one is 9-hydroxydieldrin, are excreted in the faeces. (6)
Toxicity ValuesLD50: 38 mg/kg (Oral, Rat) (4) LD50: 56 mg/kg (Dermal, Rat) (4) LD50: 49 mg/kg (Subcutaneous, Rat) (9) LD50: 9 mg/kg (Intravenous, Rat) (4) LC50: 13 mg/m3 over 4 hours (Inhalation, Rat) (9)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (8)
Uses/SourcesDieldrin is used as an insecticide. (6)
Minimum Risk LevelIntermediate Oral: 0.0001 mg/kg/day (7) Chronic Oral: 0.00005 mg/kg/day (7)
Health EffectsDieldrin is a neurotoxin and works by overstimulating the central nervous system. Ingestion of large amounts of dieldrin causes convulsions and death. However, chronic exposure to lower amounts of dieldrin also has adverse effects because dieldrin accumulates in the body. Dieldrin is known to damage the nervous system, liver, and immune system. (6)
SymptomsExposure to dieldrin results in headaches, dizziness, irritability, nausea and vomiting, cardiac arrhythmias, muscular weakness, uncontrolled muscle movements, hyperexcitability, seizures and coma. (6)
TreatmentTreatment is symptomatic, aimed at controlling convulsions, coma, and respiratory depression. If ingested, gastric lavage may be performed, followed by administering activated charcoal powder. (10)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID969491
ChEMBL IDCHEMBL1873703
ChemSpider ID10292746
KEGG IDC13718
UniProt IDNot Available
OMIM ID
ChEBI ID34696
BioCyc IDNot Available
CTD IDD004026
Stitch IDDieldrin
PDB IDNot Available
ACToR ID459
Wikipedia LinkDieldrin
References
Synthesis ReferenceNot Available
MSDST3D0017.pdf
General References
  1. Sun F, Anantharam V, Latchoumycandane C, Kanthasamy A, Kanthasamy AG: Dieldrin induces ubiquitin-proteasome dysfunction in alpha-synuclein overexpressing dopaminergic neuronal cells and enhances susceptibility to apoptotic cell death. J Pharmacol Exp Ther. 2005 Oct;315(1):69-79. Epub 2005 Jun 29. [15987830 ]
  2. Wang XF, Li S, Chou AP, Bronstein JM: Inhibitory effects of pesticides on proteasome activity: implication in Parkinson's disease. Neurobiol Dis. 2006 Jul;23(1):198-205. Epub 2006 Apr 19. [16626962 ]
  3. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
  4. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  5. Wikipedia. Dieldrin. Last Updated 25 January 2009. [Link]
  6. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for aldrin/dieldrin. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  7. 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). [Link]
  8. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  9. The Physical and Theoretical Chemistry Laboratory of Oxford University (2003). Material Safety Data Sheet (MSDS) for dieldrin. [Link]
  10. International Programme on Chemical Safety (IPCS) INCHEM (1996). Poison Information Monograph for Dieldrin. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.74 uMATG_PXRE_CISAttagene
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
  2. Kojima H, Sata F, Takeuchi S, Sueyoshi T, Nagai T: Comparative study of human and mouse pregnane X receptor agonistic activity in 200 pesticides using in vitro reporter gene assays. Toxicology. 2011 Feb 27;280(3):77-87. doi: 10.1016/j.tox.2010.11.008. Epub 2010 Nov 27. [21115097 ]
  3. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Hodges LC, Bergerson JS, Hunter DS, Walker CL: Estrogenic effects of organochlorine pesticides on uterine leiomyoma cells in vitro. Toxicol Sci. 2000 Apr;54(2):355-64. [10774817 ]
  3. Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R: Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci. 2006 Aug 15;79(12):1160-9. Epub 2006 Mar 27. [16626760 ]
  4. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R: Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci. 2006 Aug 15;79(12):1160-9. Epub 2006 Mar 27. [16626760 ]
  3. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Gaba-a receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA receptor could play a role in retinal neurotransmission.
Gene Name:
GABRR1
Uniprot ID:
P24046
Molecular Weight:
55882.91 Da
References
  1. Ratra GS, Erkkila BE, Weiss DS, Casida JE: Unique insecticide specificity of human homomeric rho 1 GABA(C) receptor. Toxicol Lett. 2002 Mar 24;129(1-2):47-53. [11879973 ]
  2. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
SNCA
Uniprot ID:
P37840
Molecular Weight:
14460.155 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for aldrin/dieldrin. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Signal transducer activity
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
Gene Name:
ATP2C1
Uniprot ID:
P98194
Molecular Weight:
100576.42 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Gene Name:
ATP2C2
Uniprot ID:
O75185
Molecular Weight:
103186.475 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular Weight:
51325.85 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA4
Uniprot ID:
P48169
Molecular Weight:
61622.645 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Transporter activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA5
Uniprot ID:
P31644
Molecular Weight:
52145.645 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA6
Uniprot ID:
Q16445
Molecular Weight:
51023.69 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRB1
Uniprot ID:
P18505
Molecular Weight:
54234.085 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB2
Uniprot ID:
P47870
Molecular Weight:
59149.895 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Gaba-gated chloride ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB3
Uniprot ID:
P28472
Molecular Weight:
54115.04 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Gaba-a receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRD
Uniprot ID:
O14764
Molecular Weight:
50707.835 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRE
Uniprot ID:
P78334
Molecular Weight:
57971.175 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRG1
Uniprot ID:
Q8N1C3
Molecular Weight:
53594.49 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRG2
Uniprot ID:
P18507
Molecular Weight:
54161.78 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRG3
Uniprot ID:
Q99928
Molecular Weight:
54288.16 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Gaba-a receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
Gene Name:
GABRP
Uniprot ID:
O00591
Molecular Weight:
50639.735 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Gaba-a receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission.
Gene Name:
GABRR2
Uniprot ID:
P28476
Molecular Weight:
54150.41 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Gaba-a receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRR3
Uniprot ID:
A8MPY1
Molecular Weight:
54271.1 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Transmembrane signaling receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRQ
Uniprot ID:
Q9UN88
Molecular Weight:
72020.875 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Pdz domain binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
Gene Name:
ATP2B1
Uniprot ID:
P20020
Molecular Weight:
138754.045 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Protein c-terminus binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
Gene Name:
ATP2B2
Uniprot ID:
Q01814
Molecular Weight:
136875.18 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Pdz domain binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
Gene Name:
ATP2B3
Uniprot ID:
Q16720
Molecular Weight:
134196.025 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Scaffold protein binding
Specific Function:
Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell (PubMed:8530416). By regulating sperm cell calcium homeostasis, may play a role in sperm motility (By similarity).
Gene Name:
ATP2B4
Uniprot ID:
P23634
Molecular Weight:
137919.03 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Protein homodimerization activity
Specific Function:
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A1
Uniprot ID:
O14983
Molecular Weight:
110251.36 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
S100 protein binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.
Gene Name:
ATP2A2
Uniprot ID:
P16615
Molecular Weight:
114755.765 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A3
Uniprot ID:
Q93084
Molecular Weight:
113976.23 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular Weight:
112895.01 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A2
Uniprot ID:
P50993
Molecular Weight:
112264.385 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A3
Uniprot ID:
P13637
Molecular Weight:
111747.51 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.
Gene Name:
ATP1A4
Uniprot ID:
Q13733
Molecular Weight:
114165.44 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.Involved in cell adhesion and establishing epithelial cell polarity.
Gene Name:
ATP1B1
Uniprot ID:
P05026
Molecular Weight:
35061.07 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
Gene Name:
ATP1B2
Uniprot ID:
P14415
Molecular Weight:
33366.925 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
Gene Name:
ATP1B3
Uniprot ID:
P54709
Molecular Weight:
31512.34 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Transporter activity
Specific Function:
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
Gene Name:
FXYD2
Uniprot ID:
P54710
Molecular Weight:
7283.265 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.97 uMATG_RARa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
Gene Name:
RARB
Uniprot ID:
P10826
Molecular Weight:
50488.63 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.17 uMATG_RARb_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.53 uMOT_SRC1_SRC1FXR_1440Odyssey Thera
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.68 uMNVS_ADME_hCYP2B6Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50341.405 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.80 uMATG_RARg_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
Gene Name:
HNF4A
Uniprot ID:
P41235
Molecular Weight:
52784.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.48 uMATG_HNF4a_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]