T3D0061 - Methoxychlor
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2009-03-06 18:58:00 UTC |
| Update Date | 2013-04-25 08:32:40 UTC |
| Accession Number | T3D0061 |
| Identification | |
| Common Name | Methoxychlor |
| 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. (R323) |
| Compound Type |
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| Chemical Structure |
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| Synonyms |
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| Chemical Formula | C16H15Cl3O2 |
| Average Molecular Weight | 345.648 |
| Monoisotopic Molecular Weight | 344.013762845 |
| Chemical IUPAC Name | methoxychlor |
| CAS Registry Number | 72-43-5 |
| SMILES | COC1=CC=C(C=C1)C(C1=CC=C(OC)C=C1)C(Cl)(Cl)Cl |
| InChI Identifier | 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 |
| InChI Key | InChIKey=IAKOZHOLGAGEJT-UHFFFAOYSA-N |
| Chemical Taxonomy | |
| Kingdom | Organic Compounds |
| Super Class | Benzenoids |
| Class | Benzene and Substituted Derivatives |
| Sub Class | Diphenylmethanes |
| Direct Parent | Diphenylmethanes |
| Alternative Parents |
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| Molecular Framework | Aromatic Homopolycyclic Compounds |
| Substituents |
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| External Descriptors |
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| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | 4115  |
| KEGG ID | C11043 |
| UniProt ID | Not Available |
| OMIM ID | Not Available |
| ChEBI ID | 6842 |
| BioCyc ID | Not Available |
| CTD ID | D008731 |
| Stitch ID | Methoxychlor |
| PDB ID | Not Available |
| ACToR ID | 843 |
| Wikipedia Link | http://en.wikipedia.org/wiki/Methoxychlor |
| Physical Properties | |
| Appearance | Pale-yellow powder. |
| Melting Point | 87 C |
| Solubility | 0.0001 mg/mL at 25 °C [RICHARDSON,LT & MILLER,DM (1960)] |
| Predicted LogP | 4.9340705153333335 |
| Toxicity Profile | |
| Route of Exposure | Oral (R323) ; dermal (R323) |
| 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 estrogen receptor alpha agonist, and also acts as an antagonist at the estrogen receptor beta and androgen receptor. This affects protein synthesis, which is believed to cause many of methoxychlor's estrogenic effects, such as decreased fertility. As methoxychlor is also a structural analogue of DDT, it is believed to have the same neurotoxic effects. This includes preventing the deactivation of the sodium gate after neuron activation and membrane depolarization, resulting in hyperexcitability of the nerve. Like DDT, methoxychlor may also inhibit neuronal adenosine triphosphatases (ATPases), particularly Na+K+-ATPase and Ca2+-ATPase, which play vital roles in neuronal repolarization. This contributes to the reduced rate of depolarization and increases the sensitivity of neurons to small stimuli that would not elicit a response in a fully depolarized neuron. (R029, R325) |
| Metabolism | Methoxychlor is well absorbed by the gastrointestinal tract and to a lesser extent by the skin. Once in the bloodstream, methoxychlor appears to distribute to most tissues of the body, with highest levels usually found in fat. Methoxychlor is metabolized rapidly by cytochrome P450 enzymes in the liver, undergoing demethylation to form phenolic derivatives, with dechlorination and dehydrochlorination reactions occurring to a lesser extent. The metabolites of methoxychlor are excreted mainly in the faeces. (R323) |
| Toxicity Values | LD50: 3460 mg/kg (Oral, Rat) (R323) |
| Lethal Dose | 6400 mg/kg for an adult human. (R324) |
| Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. (R264) |
| Uses/Sources | Methoxychlor is used as an insecticide against flies, mosquitoes, cockroaches, chiggers, and a wide variety of other insects. It is used on agricultural crops and livestock, and in animal feed, barns, grain storage bins, home garden, and on pets. (R323) |
| Minimum Risk Level | Intermediate Oral: 0.005 mg/kg/day (R260) |
| Health Effects | Animal studies show that methoxychlor may affect the reproductive system, causing harm to the ovaries, uterus, and mating cycle in females, and the testes and prostate in males, as well as decreased fertility in both sexes. Methoxychlor exposure may also cause EEG pattern changes. (R029. R323) |
| Symptoms | High levels of methoxychlor may cause fatigue, lethargy, tremors, convulsions and seizures. (R029, R323) |
| Treatment | Not Available |
| References | |
| General References |
|
Targets
1. Sodium/potassium-transporting ATPase subunit alpha-1
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.
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. (R029, R325)UniProt ID: P05023
Gene: ATP1A1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8.
[10999957 ]
2. Sodium/potassium-transporting ATPase subunit alpha-2
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.
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. (R029, R325)UniProt ID: P50993
Gene: ATP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S: Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol Pharmacol. 2000 Oct;58(4):852-8.
[10999957 ]
3. Sodium/potassium-transporting ATPase subunit alpha-3
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.
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. (R029, R325)UniProt ID: P13637
Gene: ATP1A3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
4. Sodium/potassium-transporting ATPase subunit alpha-4
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.
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. (R029, R325)UniProt ID: Q13733
Gene: ATP1A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
5. Sodium/potassium-transporting ATPase subunit beta-1
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.
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. (R029, R325)UniProt ID: P05026
Gene: ATP1B1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
6. Sodium/potassium-transporting ATPase subunit beta-2
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.
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. (R029, R325)UniProt ID: P14415
Gene: ATP1B2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
7. Sodium/potassium-transporting ATPase subunit beta-3
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.
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. (R029, R325)UniProt ID: P54709
Gene: ATP1B3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
8. Sodium/potassium-transporting ATPase subunit gamma
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
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. (R029, R325)UniProt ID: P54710
Gene: FXYD2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
9. Calcium-transporting ATPase type 2C member 1
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
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. (R029, R325)UniProt ID: P98194
Gene: ATP2C1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
10. Calcium-transporting ATPase type 2C member 2
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium (By similarity).
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. (R029, R325)UniProt ID: O75185
Gene: ATP2C2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
11. Plasma membrane calcium-transporting ATPase 1
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
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. (R029, R325)UniProt ID: P20020
Gene: ATP2B1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
12. Plasma membrane calcium-transporting ATPase 2
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
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. (R029, R325)UniProt ID: Q01814
Gene: ATP2B2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
13. Plasma membrane calcium-transporting ATPase 3
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
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. (R029, R325)UniProt ID: Q16720
Gene: ATP2B3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
14. Plasma membrane calcium-transporting ATPase 4
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
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. (R029, R325)UniProt ID: P23634
Gene: ATP2B4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
15. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
This magnesium-dependent enzyme 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.
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. (R029, R325)UniProt ID: O14983
Gene: ATP2A1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
16. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
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.
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. (R029, R325)UniProt ID: P16615
Gene: ATP2A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
17. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
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.
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. (R029, R325)UniProt ID: Q93084
Gene: ATP2A3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R325 — 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 ]
18. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
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. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).
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. (R029, R323)UniProt ID: Q9UL51
Gene: HCN2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
19. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli.
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. (R029, R323)UniProt ID: Q9Y3Q4
Gene: HCN4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
20. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
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). Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. May mediate responses to sour stimuli.
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. (R029, R323)UniProt ID: O60741
Gene: HCN1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
21. Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Putative hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions (By similarity)
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. (R029, R323)UniProt ID: Q9P1Z3
Gene: HCN3
Protein Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
22. Sodium channel protein type 1 subunit alpha
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.
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. (R029, R323)UniProt ID: P35498
Gene: SCN1A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
23. Sodium channel protein type 10 subunit alpha
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. Its electrophysiological properties vary depending on the type of the associated beta subunits (in vitro). Plays a role in neuropathic pain mechanisms (By similarity).
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. (R029, R323)UniProt ID: Q9Y5Y9
Gene: SCN10A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
24. Sodium channel protein type 11 subunit alpha
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.
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. (R029, R323)UniProt ID: Q9UI33
Gene: SCN11A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
25. Sodium channel protein type 2 subunit alpha
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.
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. (R029, R323)UniProt ID: Q99250
Gene: SCN2A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
26. Sodium channel protein type 3 subunit alpha
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.
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. (R029, R323)UniProt ID: Q9NY46
Gene: SCN3A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
27. Sodium channel protein type 4 subunit alpha
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.
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. (R029, R323)UniProt ID: P35499
Gene: SCN4A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
28. Sodium channel protein type 5 subunit alpha
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.
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. (R029, R323)UniProt ID: Q14524
Gene: SCN5A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
29. Sodium channel protein type 7 subunit alpha
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.
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. (R029, R323)UniProt ID: Q01118
Gene: SCN7A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
30. Sodium channel protein type 8 subunit alpha
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.
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. (R029, R323)UniProt ID: Q9UQD0
Gene: SCN8A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
31. Sodium channel protein type 9 subunit alpha
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).
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. (R029, R323)UniProt ID: Q15858
Gene: SCN9A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
32. Sodium channel subunit beta-1
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.
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. (R029, R323)UniProt ID: Q07699
Gene: SCN1B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
33. Sodium channel subunit beta-2
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).
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. (R029, R323)UniProt ID: O60939
Gene: SCN2B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
34. Sodium channel subunit beta-3
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).
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. (R029, R323)UniProt ID: Q9NY72
Gene: SCN3B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
35. Sodium channel subunit beta-4
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 (By similarity).
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. (R029, R323)UniProt ID: Q8IWT1
Gene: SCN4B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
- R323 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for methoxychlor. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
36. Estrogen receptor
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. Isoform 3 can bind to ERE and inhibit isoform 1.
Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)UniProt ID: P03372
Gene: ESR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- S301 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors ? and ?: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
37. Estrogen receptor beta
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. 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.
Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)UniProt ID: Q92731
Gene: ESR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- S301 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors ? and ?: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
38. Androgen receptor
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.
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. (R325)UniProt ID: P10275
Gene: AR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R325 — 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.
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