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Record Information
Version2.0
Creation Date2009-03-06 18:58:00 UTC
Update Date2014-12-24 20:21:00 UTC
Accession NumberT3D0061
Identification
Common NameMethoxychlor
ClassSmall Molecule
DescriptionMethoxychlor is a manufactured organochlorine used as an insecticide against flies, mosquitoes, cockroaches, chiggers, and a wide variety of other insects. It is used on agricultural crops and livestock, and in animal feed, barns, grain storage bins, home garden, and on pets. (6)
Compound Type
  • Aromatic Hydrocarbon
  • Ether
  • Household Toxin
  • Organic Compound
  • Organochloride
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1, 1-Bis(p-methoxyphenyl)-2,2,2-trichloroethane
1,1'-(2,2, 2-Trichloroethylidene)bis(4-methoxybenzene)
1,1'-(2,2,2-trichloroethane-1,1-diyl)bis(4-methoxybenzene)
1,1'-(2,2,2-Trichloroethylidene)bis(4-methoxybenzene)
1,1,1-Trichloro-2, 2-bis(p-anisyl)ethane
1,1,1-Trichloro-2, 2-bis(p-methoxyphenyl)ethane
1,1,1-Trichloro-2, 2-di(4-methoxyphenyl)ethane
1,1,1-Trichloro-2,2-bis(4-methoxyphenyl)ethane
1,1,1-Trichloro-2,2-bis(p-anisyl)ethane
1,1,1-Trichloro-2,2-bis(p-methoxyphenyl)ethane
1,1,1-Trichloro-2,2-bis-(p-methoxyphenyl)ethane
1,1,1-Trichloro-2,2-di(4-methoxyphenyl)ethane
1,1-Bis(p-methoxyphenyl)-2,2,2-trichloroethane
2, 2-Di(p-methoxyphenyl)-1,1,1-trichloroethane
2,2,2-t richloro-1,1-bis(4-methoxyphenyl)ethane
2,2,2-Trichloro-1,1-bis(4-methoxyphenyl)ethane
2,2-Bis (p-methoxyphenol)-1,1,1-trichloroethane
2,2-Bis(4-methoxyphenyl)-1,1,1-trichloroethane
2,2-Bis(p-anisyl)-1, 1,1-trichloroethane
2,2-Bis(p-anisyl)-1,1,1-trichloroethane
2,2-Bis(p-methoxyphenyl)-1,1, 1-trichloroethane
2,2-Bis(p-methoxyphenyl)-1,1,1-trichloroethane
2,2-Di(p-anisyl)-1,1,1-trichloroethane
2,2-Di(p-methoxyphenyl)-1,1,1-trichloroethane
2,2-Di-(p-methoxyphenyl)-1,1,1-trichloroethane
2,2-Di-p-anisyl-1,1,1-trichloroethane
4,4-(2,2,2-Trichloroethylidene)dianisole
Bis(p-anisyl)-1,1,1-trichloroethane
Bis(p-methoxyphenyl)-1,1,1-trichloroethane
Di(p-methoxyphenyl) trichloromethyl methane
Di(p-methoxyphenyl)trichloromethyl methane
Dianisyl trichloroethane
Dianisyltrichlorethane
Dianisyltrichloroethane
Dimethox ydiphenyltrichloroethane
Dimethoxy-DDT
Dimethoxy-DT
Dimethoxydiphenyltrichloroethane
Maralate
Marlate
Maxie
Meocl
Methoxcide
Methoxo
Methoxy DDT
Methoxy-DDT
Metoksychlor
p, p'-methoxychlor
p,p'-(dimethoxydiphenyl)trichloroethane
p,p'-dimethoxydiphenyltrichl oroethane
p,p'-dimethoxydiphenyltrichloroethane
p,p'-DMDT
p,p'-methoxychlor
Pmethoxychlor
Prentox
Trichloroethane dianisyl
Chemical FormulaC16H15Cl3O2
Average Molecular Mass345.648 g/mol
Monoisotopic Mass344.014 g/mol
CAS Registry Number72-43-5
IUPAC Name1-methoxy-4-[2,2,2-trichloro-1-(4-methoxyphenyl)ethyl]benzene
Traditional Namemethoxychlor
SMILESCOC1=CC=C(C=C1)C(C1=CC=C(OC)C=C1)C(Cl)(Cl)Cl
InChI IdentifierInChI=1S/C16H15Cl3O2/c1-20-13-7-3-11(4-8-13)15(16(17,18)19)12-5-9-14(21-2)10-6-12/h3-10,15H,1-2H3
InChI KeyInChIKey=IAKOZHOLGAGEJT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Phenoxy compound
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Alkyl aryl ether
  • Ether
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Alkyl halide
  • Alkyl chloride
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearancePale-yellow powder.
Experimental Properties
PropertyValue
Melting Point87°C
Boiling Pointdecomposes
Solubility0.0001 mg/mL at 25 °C [RICHARDSON,LT & MILLER,DM (1960)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility5.0e-05 g/LALOGPS
logP5.12ALOGPS
logP4.93ChemAxon
logS-6.8ALOGPS
pKa (Strongest Basic)-4.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity88.63 m³·mol⁻¹ChemAxon
Polarizability33.73 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0009000000-2e804c4f3f24a4e46581JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0009000000-516eca78c6054fdac1c9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-056s-0094000000-0899ba6b67a346aceb9aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-18acae4dc611644d1dbcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0009000000-0329df7d38acce6cb9e0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-0096000000-8cdb61fec75829abaaffJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-004i-0290000000-06ed9842894de6c2fed3JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureOral (6) ; dermal (6)
Mechanism of ToxicityCertain mono- and bis-hydroxy metabolites of methoxychlor, especially 2,2-bis(p-hydroxyphenyl)-1,1, 1-trichloroethane (HPTE), act as estrogen analogues. HPTE is an estrogen receptor alpha agonist, and also acts as an antagonist at the estrogen receptor beta and androgen receptor. This affects protein synthesis, which is believed to cause many of methoxychlor's estrogenic effects, such as decreased fertility. As methoxychlor is also a structural analogue of DDT, it is believed to have the same neurotoxic effects. This includes preventing the deactivation of the sodium gate after neuron activation and membrane depolarization, resulting in hyperexcitability of the nerve. Like DDT, methoxychlor may also inhibit neuronal adenosine triphosphatases (ATPases), particularly Na+K+-ATPase and Ca2+-ATPase, which play vital roles in neuronal repolarization. This contributes to the reduced rate of depolarization and increases the sensitivity of neurons to small stimuli that would not elicit a response in a fully depolarized neuron. (2, 1)
MetabolismMethoxychlor is well absorbed by the gastrointestinal tract and to a lesser extent by the skin. Once in the bloodstream, methoxychlor appears to distribute to most tissues of the body, with highest levels usually found in fat. Methoxychlor is metabolized rapidly by cytochrome P450 enzymes in the liver, undergoing demethylation to form phenolic derivatives, with dechlorination and dehydrochlorination reactions occurring to a lesser extent. The metabolites of methoxychlor are excreted mainly in the faeces. (6)
Toxicity ValuesLD50: 3460 mg/kg (Oral, Rat) (6)
Lethal Dose6400 mg/kg for an adult human. (3)
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (5)
Uses/SourcesMethoxychlor is used as an insecticide against flies, mosquitoes, cockroaches, chiggers, and a wide variety of other insects. It is used on agricultural crops and livestock, and in animal feed, barns, grain storage bins, home garden, and on pets. (6)
Minimum Risk LevelIntermediate Oral: 0.005 mg/kg/day (4)
Health EffectsAnimal studies show that methoxychlor may affect the reproductive system, causing harm to the ovaries, uterus, and mating cycle in females, and the testes and prostate in males, as well as decreased fertility in both sexes. Methoxychlor exposure may also cause EEG pattern changes. (2, 6)
SymptomsHigh levels of methoxychlor may cause fatigue, lethargy, tremors, convulsions and seizures. (2, 6)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID4115
ChEMBL IDCHEMBL362919
ChemSpider ID3972
KEGG IDC11043
UniProt IDNot Available
OMIM ID
ChEBI ID6842
BioCyc IDNot Available
CTD IDD008731
Stitch IDMethoxychlor
PDB IDNot Available
ACToR ID843
Wikipedia LinkMethoxychlor
References
Synthesis ReferenceNot Available
MSDST3D0061.pdf
General References
  1. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  2. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
  3. Thompson TS and Vorster SJ (2000). Attempted suicide by ingestion of methoxychlor. J Anal Toxicol 24:377-380.
  4. 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]
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  6. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [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
AC509.20 uMATG_PXRE_CISAttagene
AC503.30 uMATG_PXR_TRANSAttagene
AC508.19 uMATG_PXRE_CISAttagene
AC500.20 uMNVS_NR_hPXRNovascreen
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:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.59 uMNVS_NR_hARNovascreen
References
  1. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  2. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.70 uMATG_ERa_TRANSAttagene
AC504.00 uMATG_ERE_CISAttagene
AC503.93 uMNCGC_ERalpha_AgonistNCGC
AC504.78 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC504.39 uMATG_ERa_TRANSAttagene
AC502.73 uMOT_ERa_EREGFP_0120Odyssey Thera
AC503.21 uMOT_ERa_EREGFP_0480Odyssey Thera
AC505.62 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC505.04 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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 ]
  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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.18 uMOT_ER_ERaERb_1440Odyssey Thera
AC505.41 uMOT_ER_ERbERb_0480Odyssey Thera
AC503.52 uMOT_ER_ERbERb_1440Odyssey Thera
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
Voltage-gated sodium channel activity
Specific Function:
Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli.
Gene Name:
HCN1
Uniprot ID:
O60741
Molecular Weight:
98795.285 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).
Gene Name:
HCN2
Uniprot ID:
Q9UL51
Molecular Weight:
96949.43 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.
Gene Name:
HCN3
Uniprot ID:
Q9P1Z3
Molecular Weight:
86030.975 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli.
Gene Name:
HCN4
Uniprot ID:
Q9Y3Q4
Molecular Weight:
129040.65 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization.
Gene Name:
SCN11A
Uniprot ID:
Q9UI33
Molecular Weight:
204919.66 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN7A
Uniprot ID:
Q01118
Molecular Weight:
193491.605 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
Gene Name:
SCN8A
Uniprot ID:
Q9UQD0
Molecular Weight:
225278.005 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular Weight:
226370.175 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth.
Gene Name:
SCN1B
Uniprot ID:
Q07699
Molecular Weight:
24706.955 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).
Gene Name:
SCN2B
Uniprot ID:
O60939
Molecular Weight:
24325.69 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Gene Name:
SCN3B
Uniprot ID:
Q9NY72
Molecular Weight:
24702.08 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the suceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.
Gene Name:
SCN4B
Uniprot ID:
Q8IWT1
Molecular Weight:
24968.755 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.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
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. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8. [10999957 ]
  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:
Zinc ion binding
Specific Function:
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
Gene Name:
NR1I3
Uniprot ID:
Q14994
Molecular Weight:
39942.145 Da
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
References
  1. Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [14579009 ]
General Function:
Ubiquitin protein ligase binding
Specific Function:
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_hDFCGF_EGFR_upBioSeek
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:
Prostaglandin e receptor activity
Specific Function:
Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle.
Gene Name:
PTGER2
Uniprot ID:
P43116
Molecular Weight:
39759.945 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_LPS_PGE2_downBioSeek
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:
Transcriptional activator activity, rna polymerase ii distal enhancer sequence-specific binding
Specific Function:
Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.
Gene Name:
NFE2L2
Uniprot ID:
Q16236
Molecular Weight:
67825.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.80 uMATG_NRF2_ARE_CISAttagene
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
AC505.14 uMCLZD_CYP2B6_6CellzDirect
AC505.75 uMCLZD_CYP2B6_24CellzDirect
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:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.75 uMCLZD_CYP1A2_6CellzDirect
AC506.30 uMCLZD_CYP1A2_24CellzDirect
AC505.62 uMCLZD_CYP1A2_48CellzDirect
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:
Vitamin d 24-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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.00 uMCLZD_CYP1A1_6CellzDirect
AC506.93 uMCLZD_CYP1A1_48CellzDirect
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:
Vitamin d3 25-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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.58 uMCLZD_CYP3A4_6CellzDirect
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 binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.59 uMCLZD_UGT1A1_24CellzDirect
AC509.74 uMCLZD_UGT1A1_48CellzDirect
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:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.91 uMNVS_ADME_hCYP2C19Novascreen
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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.30 uMNVS_ADME_hCYP2C9Novascreen
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 ]