O,P'-DDD (T3D0151)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (43)XML
Targets (43)
Record Information
Version2.0
Creation Date2009-03-06 18:58:10 UTC
Update Date2014-12-24 20:21:13 UTC
Accession NumberT3D0151
Identification
Common NameO,P'-DDD
ClassSmall Molecule
DescriptionDDD, O,P'- is an isomer of dichlorodiphenyldichloroethane, an organochlorine insecticide. It is a component of commercial mixtures of DDT. DDT was once a widely used pesticide, but today its agricultural use has been banned worldwide due to its toxicity and tendency to bioaccumulate. However, it still has limited use in disease vector control. (2). It is a derivative of the insecticide dichlorodiphenyldichloroethane that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression. [PubChem]
Compound Type
  • Antineoplastic Agent, Hormonal
  • Drug
  • Organic Compound
  • Organochloride
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Lisodren
Lysodren
Mitotan
Mitotane
Mitotano
Mitotanum
O,P'-ddd
Opeprim
Chemical FormulaC14H10Cl4
Average Molecular Mass320.041 g/mol
Monoisotopic Mass317.954 g/mol
CAS Registry Number53-19-0
IUPAC Name1-chloro-4-[2,2-dichloro-1-(2-chlorophenyl)ethyl]benzene
Traditional Namemitotane
SMILESClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl
InChI IdentifierInChI=1/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H
InChI KeyInChIKey=JWBOIMRXGHLCPP-UHFFFAOYNA-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
  • Halobenzene
  • Chlorobenzene
  • Aryl halide
  • Aryl chloride
  • Hydrocarbon derivative
  • Organochloride
  • Organohalogen compound
  • Alkyl halide
  • Alkyl chloride
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
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
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point77°C
Boiling PointNot Available
Solubility0.1 mg/L (at 25°C)
LogP6
Predicted Properties
PropertyValueSource
Water Solubility9.4e-06 g/LALOGPS
logP6.08ALOGPS
logP6.11ChemAxon
logS-7.5ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity79.97 m³·mol⁻¹ChemAxon
Polarizability29.93 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-Q (Non-derivatized)splash10-000i-2590000000-2d3f8090ffa4733bf9ee2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-Q (Non-derivatized)splash10-000i-2590000000-2d3f8090ffa4733bf9ee2018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0019-3190000000-3e8980db36b0ac7be7c92017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0029000000-a8fe8b7a30127f18cfcf2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0029000000-b5f28037c9691eb240472016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ac0-0790000000-fe84d84c9218b81962922016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009000000-eddb407ee0b99900a0ec2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0229000000-967d4bba6420d7542b782016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01q9-0390000000-de32116845b75e0077f52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0039000000-3c403b01150c1ceb18132021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0091000000-a71d76ec2ab1019a49272021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0290000000-251e3f81d8a1025f44362021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0039000000-90d3b740113c4fec06c32021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0159-1096000000-d8dfb53c7c6dd6d1051a2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9160000000-978ead17186c9fd3851c2021-10-11View Spectrum
MSMass Spectrum (Electron Ionization)splash10-000i-2690000000-770065ddc57899130a312014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 50.32 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureOral (3); about 40% oral Lysodren is absorbed.
Mechanism of ToxicityDDD toxicity occurs via at least four mechanisms, possibly all functioning simultaneously. DDD reduces potassium transport across the membrane. DDD inhibits the inactivation of voltaged-gated sodium channels. The channels activate (open) normally but are inactivated (closed) slowly, thus interfering with the active transport of sodium out of the nerve axon during repolarization and resulting in a state of hyperexcitability. DDD inhibits neuronal adenosine triphosphatases (ATPases), particularly Na+K+-ATPase, and Ca2+-ATPase which play vital roles in neuronal repolarization. DDD also inhibits the ability of calmodulin, a calcium mediator in nerves, to transport calcium ions that are essential for the release of neurotransmitters. All these inhibited functions reduce the rate of depolarization and increase the sensitivity of neurons to small stimuli that would not elicit a response in a fully depolarized neuron. DDD is also believed to adversely affect the reproductive system by mimicking endogenous hormones and binding to the estrogen and adrogen receptors. (1, 3)
MetabolismDDD is absorbed in the stomach and intestine, after which it enters the lymphatic system and is carried throughout the body and incorporated into fatty tissues. Metabolism of DDD occurs mainly via cytochrome P-450 enzymes in the liver and kidney. Its metabolites, mainly DDA (bis(p-chlorophenyl) acetic acid), are excreted in the urine. (3) Route of Elimination: A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues. Half Life: 18-159 days
Toxicity ValuesLD50: 113 mg/kg (Oral, Rat) (5)
Lethal Dose5 g/kg for an adult human. (5)
Carcinogenicity (IARC Classification)Not directly listed by IARC, but carcinogenicity studies of this DDT metabolite are discussed in connection with DDT (7).
Uses/SourcesDDD is found in DDT, which is used as a pesticide and in disease vector control. (2). It is also used for treatment of inoperable adrenocortical tumours; Cushing's syndrome
Minimum Risk LevelNot Available
Health EffectsDDT has been shown to cause mild anemia. Exposure to DDT causes loss of weight and anorexia. DDT poisoning affects CNS function in humans, but pathologic changes are observed in the liver and reproductive organs. Hypertrophy of hepatocytes and subcellular organelles such as mitochondria, proliferation of smooth endoplasmic reticulum, centrolobular necrosis after exposure to high concentrations, and an increase in the incidence of hepatic tumors have been noted. (1)
SymptomsDDT exposure causes ataxia and abnormal stepping. Acute signs of DDT poisoning include paresthesia after oral ingestion. Studies have shown that a mammal poisoned with DDT-type agents displays periodic persistent tremoring and/or convulsive seizures that are suggestive of repetitive discharges in neurons. These repetitive tremors and seizures can be initiated by tactile and auditory stimuli. (1)
TreatmentTreatment of DDT exposure should be primarily directed towards decontamination and supportive care, as there is no specific antidote. The use of gastric lavage and activated charcoal for large ingestions may be effective. (6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00648
HMDB IDNot Available
PubChem Compound ID4211
ChEMBL IDCHEMBL1670
ChemSpider ID4066
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDD008939
Stitch IDDDD, O,P'-
PDB IDNot Available
ACToR ID378
Wikipedia LinkMitotane
References
Synthesis ReferenceNot Available
MSDST3D0151.pdf
General 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. Wikipedia. DDT. Last Updated 2 April 2009. [Link]
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for DDT, DDE, and DDD. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  4. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  5. HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). [Link]
  6. International Programme on Chemical Safety (IPCS) INCHEM (1992). Poison Information Monograph for DDT. [Link]
  7. International Agency for Research on Cancer. 1991. Occupational Exposures in Insecticide Application, and Some Pesticides. IARC monograph, volume 53. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Estrogen receptor
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
AC501.95 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC505.30 uMATG_ERa_TRANSAttagene
AC509.34 uMOT_ER_ERaERa_0480Odyssey Thera
AC501.91 uMOT_ERa_EREGFP_0120Odyssey Thera
AC502.02 uMOT_ERa_EREGFP_0480Odyssey Thera
AC507.63 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC501.85 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. 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 ]
  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.
Target Details
2. Estrogen receptor beta
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
AC506.31 uMOT_ER_ERaERb_0480Odyssey Thera
AC506.82 uMOT_ER_ERaERb_1440Odyssey Thera
AC504.53 uMOT_ER_ERbERb_0480Odyssey Thera
AC505.82 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. 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 ]
  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.
Target Details
3. Adrenodoxin, mitochondrial
General Function:
Iron ion binding
Specific Function:
Participates in the synthesis of thyroid hormones. Essential for the synthesis of various steroid hormones, participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis. Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage.
Gene Name:
FDX1
Uniprot ID:
P10109
Molecular Weight:
19392.475 Da
References
  1. Kandul SV, Iatsyk MI, Kononenko VIa: [Comparative study of the effect of chloditan on the concentration of cytochrome P-450 and adrenodoxin in various organs of the dog and rat]. Fiziol Zh. 1986 Sep-Oct;32(5):579-84. [3770229 ]
  2. Cabrini DA, Campos MM, Tratsk KS, Merino VF, Silva JA Jr, Souza GE, Avellar MC, Pesquero JB, Calixto JB: Molecular and pharmacological evidence for modulation of kinin B(1) receptor expression by endogenous glucocorticoids hormones in rats. Br J Pharmacol. 2001 Jan;132(2):567-77. [11159707 ]
  3. Cai W, Counsell RE, Schteingart DE, Sinsheimer JE, Vaz AD, Wotring LL: Adrenal proteins bound by a reactive intermediate of mitotane. Cancer Chemother Pharmacol. 1997;39(6):537-40. [9118466 ]
Target Details
4. Androgen receptor
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
References
  1. Maness SC, McDonnell DP, Gaido KW: Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells. Toxicol Appl Pharmacol. 1998 Jul;151(1):135-42. [9705896 ]
  2. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for DDT, DDE, and DDD. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
5. Calcium-transporting ATPase type 2C member 1
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.
Target Details
6. Calcium-transporting ATPase type 2C member 2
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.
Target Details
7. Calmodulin
General Function:
Titin binding
Specific Function:
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.
Gene Name:
CALM1
Uniprot ID:
P0DP23
Molecular Weight:
16837.47 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.
Target Details
8. Cytochrome P450 11B1, mitochondrial
General Function:
Steroid 11-beta-monooxygenase activity
Specific Function:
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
Gene Name:
CYP11B1
Uniprot ID:
P15538
Molecular Weight:
57572.44 Da
References
  1. Lindhe O, Skogseid B, Brandt I: Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis. J Clin Endocrinol Metab. 2002 Mar;87(3):1319-26. [11889204 ]
Target Details
9. Plasma membrane calcium-transporting ATPase 1
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.
Target Details
10. Plasma membrane calcium-transporting ATPase 2
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.
Target Details
11. Plasma membrane calcium-transporting ATPase 3
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.
Target Details
12. Plasma membrane calcium-transporting ATPase 4
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.
Target Details
13. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
14. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
15. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
16. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
17. Progesterone receptor
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 ]
Target Details
18. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
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.
Target Details
19. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
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.
Target Details
20. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
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.
Target Details
21. Sodium channel protein type 1 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
22. Sodium channel protein type 10 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
23. Sodium channel protein type 11 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
24. Sodium channel protein type 2 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
25. Sodium channel protein type 3 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
26. Sodium channel protein type 4 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
27. Sodium channel protein type 5 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
28. Sodium channel protein type 7 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
29. Sodium channel protein type 8 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
30. Sodium channel protein type 9 subunit alpha
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
31. Sodium channel subunit beta-1
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
32. Sodium channel subunit beta-2
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
33. Sodium channel subunit beta-3
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
34. Sodium channel subunit beta-4
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. Davies TG, Field LM, Usherwood PN, Williamson MS: DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007 Mar;59(3):151-62. [17487686 ]
Target Details
35. Sodium/potassium-transporting ATPase subunit alpha-1
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.
Target Details
36. Sodium/potassium-transporting ATPase subunit alpha-2
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.
Target Details
37. Sodium/potassium-transporting ATPase subunit alpha-3
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.
Target Details
38. Sodium/potassium-transporting ATPase subunit alpha-4
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.
Target Details
39. Sodium/potassium-transporting ATPase subunit beta-1
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.
Target Details
40. Sodium/potassium-transporting ATPase subunit beta-2
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.
Target Details
41. Sodium/potassium-transporting ATPase subunit beta-3
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.
Target Details
42. Sodium/potassium-transporting ATPase subunit gamma
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.
Target Details
43. Nuclear receptor subfamily 1 group I member 2
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
AC505.37 uMATG_PXR_TRANSAttagene
AC504.50 uMATG_PXRE_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 ]