Methoxychlor
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Basic Info
| Common Name | Methoxychlor(F03315) |
| 2D Structure | |
| Description | Methoxychlor 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. (L167) |
| FRCD ID | F03315 |
| CAS Number | 72-43-5 |
| PubChem CID | 4115 |
| Formula | C16H15Cl3O2 |
| IUPAC Name | 1-methoxy-4-[2,2,2-trichloro-1-(4-methoxyphenyl)ethyl]benzene |
| InChI Key | IAKOZHOLGAGEJT-UHFFFAOYSA-N |
| InChI | InChI=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 |
| Canonical SMILES | COC1=CC=C(C=C1)C(C2=CC=C(C=C2)OC)C(Cl)(Cl)Cl |
| Isomeric SMILES | COC1=CC=C(C=C1)C(C2=CC=C(C=C2)OC)C(Cl)(Cl)Cl |
| Wikipedia | Methoxychlor |
| Synonyms |
methoxychlor
p,p'-Methoxychlor
72-43-5
DMDT
Dimethoxy-DDT
Methoxy-DDT
Methoxcide
Metox
Maralate
Marlate
|
| Classifies |
Pollutant
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Diphenylmethanes |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Diphenylmethanes |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| 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 |
| Description | This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 345.644 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 4 |
| Complexity | 279 |
| Monoisotopic Mass | 344.014 |
| Exact Mass | 344.014 |
| XLogP | 5.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 21 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9642 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.8326 |
| P-glycoprotein Substrate | Non-substrate | 0.7443 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8782 |
| Non-inhibitor | 0.8336 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8131 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.9029 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7678 |
| CYP450 2D6 Substrate | Non-substrate | 0.8070 |
| CYP450 3A4 Substrate | Substrate | 0.5546 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.8275 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7450 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9089 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.9397 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.6862 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8873 |
| Non-inhibitor | 0.8249 | |
| AMES Toxicity | Non AMES toxic | 0.9133 |
| Carcinogens | Non-carcinogens | 0.6423 |
| Fish Toxicity | High FHMT | 0.9285 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9992 |
| Honey Bee Toxicity | High HBT | 0.9063 |
| Biodegradation | Not ready biodegradable | 0.9460 |
| Acute Oral Toxicity | III | 0.8419 |
| Carcinogenicity (Three-class) | Non-required | 0.6943 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -6.8067 | LogS |
| Caco-2 Permeability | 1.6284 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.2386 | LD50, mol/kg |
| Fish Toxicity | -0.3140 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.9560 | pIGC50, ug/L |
MRLs
| Food | Product Code | Country | MRLs | Application Date | Notes |
|---|---|---|---|---|---|
| Wheat (Durum wheat, Einkorn wheat/small spelt/one-grain wheat, Emmer wheat, Khorasan wheat, Spelt, Triticale, Other species of genus Triticum, not elsewhere mentioned,) | 0500090 | European Union | 0.01* | 01/09/2008 | |
| Carrots | Korea | 14ppm | |||
| Peanuts | Korea | 14ppm | |||
| Cucumbers | Korea | 14ppm | |||
| Lettuce | Korea | 14ppm | |||
| Wheat | Korea | 2ppm | |||
| Apricots | Korea | 14ppm | |||
| Oats | Korea | 2ppm | |||
| Cherries | Korea | 14ppm | |||
| Kale | Korea | 14ppm | |||
| Rose (Almond, Bee balm, Bitter orange/sour orange, Black locust, Cat’s foot, Chrysanthemum, Cinnamon, Clary sage, Cornflower, Cowslip/primrose, Daisy, Dyer’s broom, Elder, Field poppy, Great mullei... | 0631030 | European Union | 0.1* | 01/09/2008 | |
| Maize | Korea | 2ppm | |||
| Strawberry (Absinth/common wormwood, Agrimony, Alfalfa/lucerne, Aloe (leaf gel), Alpine ladies mantle, Bearberry, Bilberry/European blueberry/whortleberry, Birch, Bitter orange/sour orange, Blackbe... | 0632010 | European Union | 0.1* | 01/09/2008 | |
| Pine nut kernels (Pine nut kernels from other species than Pinus pinea, Pine nut kernels from other species than Pinus pinea, Pine nut kernels from other species than Pinus pinea, Pine nut kernels ... | 0120090 | European Union | 0.01* | 01/09/2008 | |
| Basil and edible flowers (Apple mint, Asiatic pennywort, Bergamot mint/eau-de-Cologne mint, Corsican mint, Courgette (edible flowers), Gingermint, Greek bush basil, Hoary basil, Holy basil/tulsi, L... | 0256080 | European Union | 0.01* | 01/09/2008 | |
| FRUITS, FRESH or FROZEN; TREE NUTS | 0100000 | European Union | 0.01* | 01/09/2008 | |
| Citrus fruits | 0110000 | European Union | 0.01* | 01/09/2008 | |
| Grapefruits (Natsudaidais, Shaddocks/pomelos, Sweeties/oroblancos, Tangelolos, Tangelos (except minneolas)/Ugli®, Other hybrids of Citrus paradisi, not elsewhere mentioned,) | 0110010 | European Union | 0.01* | 01/09/2008 | |
| Oranges (Bergamots, Bitter oranges/sour oranges, Blood oranges, Cara caras, Chinottos, Trifoliate oranges, Other hybrids of Citrus sinensis, not elsewhere mentioned,) | 0110020 | European Union | 0.01* | 01/09/2008 | |
| Lemons (Buddha's hands/Buddha's fingers, Citrons,) | 0110030 | European Union | 0.01* | 01/09/2008 |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Distribution and risk assessment of banned and other current-use pesticides insurface and groundwaters consumed in an agricultural catchment dominated by cocoacrops in the Ankobra Basin, Ghana. | Sci Total Environ | 2018 Aug 15 | 29597160 |
| Residues of organochlorine pesticides in surface soil and raw foods from ruralareas of the Republic of Tajikistan. | Environ Pollut | 2017 May | 28237311 |
| Pesticide Residues in Honey from the Major Honey Producing Forest Belts in Ghana. | J Environ Public Health | 2017 | 28951746 |
| Risk Assessment of Organochlorines in Mollusk from the Mediterranean and Red Sea Coasts of Egypt. | Water Environ Res | 2016 Apr | 27131056 |
| Assessment of health risk from organochlorine xenobiotics in goat milk forconsumers in Poland. | Chemosphere | 2016 Apr | 26829307 |
| Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study. | Biomed Res Int | 2016 | 27800487 |
| Estimation of human health risk associated with the consumption ofpesticide-contaminated vegetables from Kumasi, Ghana. | Environ Monit Assess | 2015 May | 25864079 |
| Organochlorine pesticides and their metabolites in human breast milk fromShanghai, China. | Environ Sci Pollut Res Int | 2015 Jun | 25595932 |
| Organochlorine and organophosphorus pesticide residues in raw buffalo milk fromagroindustrial areas in Assiut, Egypt. | Environ Toxicol Pharmacol | 2015 Jan | 25575291 |
| Effects of short-term oral combined exposure to environmental immunotoxicchemicals in mice. | J Immunotoxicol | 2014 Oct | 24188624 |
| Mercury and Chlorinated Pesticides on the Highest Level of the Food Web asExemplified by Herring from the Southern Baltic and African Penguins from theZoo. | Water Air Soil Pollut | 2013 May | 23687395 |
| Risk posed by chlorinated organic compounds in Abu Qir Bay, East Alexandria,Egypt. | Environ Sci Pollut Res Int | 2012 Mar | 21948127 |
| Two-generation reproduction toxicity study in rats with methoxychlor. | Congenit Anom (Kyoto) | 2012 Mar | 22348781 |
| Endocrine disrupters: a review of some sources, effects, and mechanisms ofactions on behaviour and neuroendocrine systems. | J Neuroendocrinol | 2012 Jan | 21951193 |
| Reductive dechlorination of methoxychlor by bacterial species of environmentalorigin: evidence for primary biodegradation of methoxychlor in submergedenvironments. | J Agric Food Chem | 2012 Feb 29 | 22292429 |
| Concentrations of trace elements [corrected] and organochlorines in Mutton bird (Puffinus griseus). | Ecotoxicol Environ Saf | 2011 Sep | 21676460 |
| Organochlorine pesticide residues in strawberries from integrated pest managementand organic farming. | J Agric Food Chem | 2011 Jul 27 | 21235274 |
| Pesticide residues in fruits at the market level in Accra Metropolis, Ghana, apreliminary study. | Environ Monit Assess | 2011 Apr | 20559713 |
| Neuroendocrine impacts of endocrine-disrupting chemicals in birds: life stage and species sensitivities. | J Toxicol Environ Health B Crit Rev | 2011 | 21790319 |
| Organochlorine pesticide residues in wheat from Konya region, Turkey. | Food Chem Toxicol | 2010 May | 20156519 |
Targets
- 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
References
- 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
References
- 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. 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
- Mechanism of Action:
- Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- 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
References
- 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:
- 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
- Mechanism of Action:
- 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.
References
- 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 potassium channel. May also facilitate the permeation of sodium ions.
- Gene Name:
- HCN3
- Uniprot ID:
- Q9P1Z3
- Molecular Weight:
- 86030.975 Da
- Mechanism of Action:
- 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.
References
- 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 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
- Mechanism of Action:
- 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.
References
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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:
- SCN2A
- Uniprot ID:
- Q99250
- Molecular Weight:
- 227972.64 Da
- Mechanism of Action:
- 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.
References
- 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:
- SCN3A
- Uniprot ID:
- Q9NY46
- Molecular Weight:
- 226291.905 Da
- Mechanism of Action:
- 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.
References
- 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:
- 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
- Mechanism of Action:
- 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.
References
- 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:
- SCN7A
- Uniprot ID:
- Q01118
- Molecular Weight:
- 193491.605 Da
- Mechanism of Action:
- 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.
References
- 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. 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
- Mechanism of Action:
- 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.
References
- 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 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
- Mechanism of Action:
- 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.
References
- 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 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
- Mechanism of Action:
- 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.
References
- 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 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
- Mechanism of Action:
- 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.
References
- 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 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
- Mechanism of Action:
- 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.
References
- Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A1
- Uniprot ID:
- P05023
- Molecular Weight:
- 112895.01 Da
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- 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:
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
- 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
References
- 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
References
- 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
References
- 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
References
- 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 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
References
- 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:
- 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
- Mechanism of Action:
- Certain 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 know androgen receptor antagonist.
References
- 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 ]
- 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
- Mechanism of Action:
- Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
- Mechanism of Action:
- 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.
References
- 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:
- 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
- Mechanism of Action:
- 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.
References
- 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 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
- Mechanism of Action:
- 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.
References
- 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. 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
- Mechanism of Action:
- 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.
References
- 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
- Mechanism of Action:
- 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.
References
- 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 ]
- 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
References
- 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
References
- 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
References
- 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 ]