T3D0093 - Hexachlorobenzene
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2009-03-06 18:58:04 UTC |
| Update Date | 2013-04-25 08:32:48 UTC |
| Accession Number | T3D0093 |
| Identification | |
| Common Name | Hexachlorobenzene |
| Description | Hexachlorobenzene is a chlorinated hydrocarbon previously used as a pesticide to protect the seeds of onions and sorghum, wheat, and other grains against fungus. It has since been banned due to its nature as a persistent organic pollutant. It was also used to make fireworks, ammunition, and synthetic rubber. (R435) |
| Compound Type |
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| Chemical Structure |
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| Synonyms |
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| Chemical Formula | C6Cl6 |
| Average Molecular Weight | 284.782 |
| Monoisotopic Molecular Weight | 281.813116242 |
| Chemical IUPAC Name | hexachlorobenzene |
| CAS Registry Number | 118-74-1 |
| SMILES | ClC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl |
| InChI Identifier | InChI=1S/C6Cl6/c7-1-2(8)4(10)6(12)5(11)3(1)9 |
| InChI Key | InChIKey=CKAPSXZOOQJIBF-UHFFFAOYSA-N |
| Chemical Taxonomy | |
| Kingdom | Organic Compounds |
| Super Class | Benzenoids |
| Class | Benzene and Substituted Derivatives |
| Sub Class | Halobenzenes |
| Direct Parent | Chlorobenzenes |
| Alternative Parents |
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| Molecular Framework | Aromatic Homomonocyclic Compounds |
| Substituents |
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| External Descriptors |
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| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | 8370  |
| KEGG ID | C11042 |
| UniProt ID | Not Available |
| OMIM ID | Not Available |
| ChEBI ID | 5692 |
| BioCyc ID | CPD-1125 |
| CTD ID | D006581 |
| Stitch ID | Hexachlorobenzene |
| PDB ID | Not Available |
| ACToR ID | 691 |
| Wikipedia Link | Not Available |
| Physical Properties | |
| Appearance | Not Available |
| Melting Point | 231.8 C |
| Solubility | 6.2e-06 mg/mL at 25 °C [FARMER,WJ et al. (1976)] |
| Predicted LogP | 5.5975138740000006 |
| Toxicity Profile | |
| Route of Exposure | Oral (R435); inhalation (R435) ; dermal (R435) |
| Mechanism of Action | Hexachlorobenzene causes porphyria by modifying sulfhydryl groups in the catalytic or substrate-binding sites of uroporphyrinogen decarboxylase. This inhibits uroporphyrinogen decarboxylase, resulting in a deficiency of the decarboxylation of uroporphyrinogen III and accumulation of uroporphyrins in the liver. In addition, metabolism of hexachlorobenzene by the cytochrome P-450 enzymes is believed to produce reactive electrophilic metabolites that covalently bind to cellular proteins and DNA, causing irreversible damage. Exposure to hexochlorobenzene also causes macrophages to be attracted to organs such as the spleen, lungs, and skin, where they become activated by the hexochlorobenzene. This leads to a cascade of reactions involving innate immune cells. The gene expression profiles provide evidence for the importance of macrophages and granulocytes and mediators released by these cells in the adverse inflammatory response against hexochlorobenzene. In this way, co-stimulatory or danger signals are generated that could polyclonally activate T cells. Hexachlorobenzene is a weak agonist for aryl hydrocarbon receptor and may exhibit some of its toxic effects by activating the gene-regulatory properties of this protein, possibly inducing cytochome P-450 enzymes. It may also act at certain endocrine receptors. (R044, R435, R437, R439, R188) |
| Metabolism | Hexachlorobenzene is mainly absorbed via ingestion, but also through inhalation and oral routes. It preferentially distributes to adipose tissue and other organs with high fat content. In animals, hexachlorobenzene is slowly metabolized to pentachlorophenol by the hepatic cytochrome P-450 system, conjugated with glutathione to yield pentachlorothiophenol, or reductively dechlorinated to form pentachlorobenzene. Other metabolites include less chlorinated benzenes, chlorophenols, S-conjugated phenols, and benzenes. Hexachlorobenzene is slowly metabolized in mammals, and the majority of hexachlorobenzene is excreted unchanged in the feces, while metabolites are excreted in the urine. (R435) |
| Toxicity Values | LD50: 3500 mg/kg (Oral, Rat) (R029) |
| Lethal Dose | Not Available |
| Carcinogenicity (IARC Classification) | 2B, possibly carcinogenic to humans. (R264) |
| Uses/Sources | Hexachlorobenzene was previously used as a pesticide to protect the seeds of onions and sorghum, wheat, and other grains against fungus. It was also used to make fireworks, ammunition, and synthetic rubber. As it can persist in the environment for long periods of time, today exposure occurs mainly from contact with contaminated water, food, soil, or air. (R435) |
| Minimum Risk Level | Acute Oral: 0.008 mg/kg/day (R260) Intermediate Oral: 0.0001 mg/kg/day (R260) Chronic Oral: 0.00005 mg/kg/day (R260) |
| Health Effects | Chronic exposure to hexachlorobenzene can damage the liver, thyroid, nervous system, bones, kidneys, blood, and immune and endocrine systems. It also causes a syndrome, called black sore, that is characterized by dermal blistering and epidermolysis, pigmentation and scarring, alopecia, photosensitivity, hepatomegaly, porphyria, suppurative arthritis, osteomyelitis, and osteoporosis of the bones of the hands. It may also cause a liver disease called porphyria cutanea tarda. This disease can cause red-colored urine, skin sores, change in skin color, arthritis, and problems of the liver, nervous system, and stomach. Hexachlorobenzene also affects development and results in lower survival rates of children of exposed mothers. It is also believed to be a human carcinogen. (R029, R435) |
| Symptoms | Hexachlorobenzene causes a syndrome, called black sore, that is characterized by dermal blistering and epidermolysis, pigmentation and scarring, alopecia, photosensitivity, hepatomegaly, porphyria, suppurative arthritis, osteomyelitis, and osteoporosis of the bones of the hands. It may also cause a liver disease called porphyria cutanea tarda. This disease can cause red-colored urine, skin sores, change in skin color, arthritis, and problems of the liver, nervous system, and stomach. (R435) |
| Treatment | Treatment is mainly symptomatic and may include gastric lavage, administering activated charcoal, and controlling convulsions. (R436) |
| References | |
| General References |
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Targets
1. Uroporphyrinogen decarboxylase
Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III.
Hexachlorobenzene causes porphyria by modifying sulfhydryl groups in the catalytic or substrate-binding sites of uroporphyrinogen decarboxylase. This inhibits uroporphyrinogen decarboxylase, resulting in a deficiency of the decarboxylation of uroporphyrinogen III and accumulation of uroporphyrins in the liver. (R437)UniProt ID: P06132
Gene: UROD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R437 — Chaufan G, Rios de Molina MC, San Martin de Viale LC: How does hexachlorobenzene treatment affect liver uroporphyrinogen decarboxylase? Int J Biochem Cell Biol. 2001 Jun;33(6):621-30.
[11378443 ]
2. Aryl hydrocarbon receptor
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues.
Hexachlorobenzene is a weak agonist for aryl hydrocarbon receptor and may exhibit some of its toxic effects by activating the gene-regulatory properties of this protein, possibly inducing cytochome P-450 enzymes. (R439)UniProt ID: P35869
Gene: AHR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R439 — Hahn ME, Goldstein JA, Linko P, Gasiewicz TA: Interaction of hexachlorobenzene with the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro and in vivo. Evidence that hexachlorobenzene is a weak Ah receptor agonist. Arch Biochem Biophys. 1989 Apr;270(1):344-55.
[2539049 ]
3. Estrogen-related receptor gamma
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).
Hexachlorobenzene is an antagonist for the estrogen-related receptor gamma. (R440)UniProt ID: P62508
Gene: ESRRG
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R188 — Li J, Li N, Ma M, Giesy JP, Wang Z: In vitro profiling of the endocrine disrupting potency of organochlorine pesticides. Toxicol Lett. 2008 Dec 15;183(1-3):65-71. Epub 2008 Oct 17.
[18992306 ]
4. 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.
Hexachlorobenzene is an antagonist for the androgren receptor. (R440)UniProt ID: P10275
Gene: AR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R188 — Li J, Li N, Ma M, Giesy JP, Wang Z: In vitro profiling of the endocrine disrupting potency of organochlorine pesticides. Toxicol Lett. 2008 Dec 15;183(1-3):65-71. Epub 2008 Oct 17.
[18992306 ]
5. Cytokine receptor common subunit beta
High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.
Metabolism of hexachlorobenzene by the cytochrome P-450 enzymes is believed to produce reactive electrophilic metabolites that covalently bind to cellular proteins and DNA, causing irreversible damage. (R435)UniProt ID: P32927
Gene: CSF2RB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R435 — ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for hexachlorobenzene. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
6. Calcium-transporting ATPase type 2C member 1
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
7. Calcium-transporting ATPase type 2C member 2
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium (By similarity).
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
8. Gamma-aminobutyric acid receptor subunit alpha-1
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P14867
Gene: GABRA1
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.
9. Gamma-aminobutyric acid receptor subunit alpha-2
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P47869
Gene: GABRA2
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.
10. Gamma-aminobutyric acid receptor subunit alpha-3
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P34903
Gene: GABRA3
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.
11. Gamma-aminobutyric acid receptor subunit alpha-4
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P48169
Gene: GABRA4
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.
12. Gamma-aminobutyric acid receptor subunit alpha-5
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P31644
Gene: GABRA5
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.
13. Gamma-aminobutyric acid receptor subunit alpha-6
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: Q16445
Gene: GABRA6
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.
14. Gamma-aminobutyric acid receptor subunit beta-1
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P18505
Gene: GABRB1
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.
15. Gamma-aminobutyric acid receptor subunit beta-2
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P47870
Gene: GABRB2
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.
16. Gamma-aminobutyric acid receptor subunit beta-3
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P28472
Gene: GABRB3
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.
17. Gamma-aminobutyric acid receptor subunit delta
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: O14764
Gene: GABRD
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.
18. Gamma-aminobutyric acid receptor subunit epsilon
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P78334
Gene: GABRE
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.
19. Gamma-aminobutyric acid receptor subunit gamma-1
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: Q8N1C3
Gene: GABRG1
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.
20. Gamma-aminobutyric acid receptor subunit gamma-2
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P18507
Gene: GABRG2
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.
21. Gamma-aminobutyric acid receptor subunit gamma-3
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: Q99928
Gene: GABRG3
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.
22. Gamma-aminobutyric acid receptor subunit pi
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: O00591
Gene: GABRP
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.
23. Gamma-aminobutyric acid receptor subunit rho-1
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA receptor could play a role in retinal neurotransmission.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P24046
Gene: GABRR1
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.
24. Gamma-aminobutyric acid receptor subunit rho-2
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: P28476
Gene: GABRR2
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.
25. Gamma-aminobutyric acid receptor subunit rho-3
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel (By similarity).
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: A8MPY1
Gene: GABRR3
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.
26. Gamma-aminobutyric acid receptor subunit theta
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)UniProt ID: Q9UN88
Gene: GABRQ
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.
27. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
28. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
29. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
30. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
31. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
32. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
33. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
34. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
35. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
36. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
37. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
38. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
39. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
40. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
41. 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.
This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)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.
42. 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.
43. 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.