Record Information
Version 1.0
Creation Date 2009-03-06 11:57:55 -0700
Update Date 2014-08-11 11:53:57 -0600
Accession Number T3D0016
Identification
Common Name Trichloroethylene
Description Trichloroethylene is a chemical compound produced from ethylene. It was originally used as an anaethetic before its toxicity was recognized. Today it is mainly used as an industrial solvent, especially for removing grease from metal parts. It is one ingredient of cigarette. (L14)
Compound Type
  • Organic Compound
  • Organochloride
  • Solvent
  • Anesthetic
Chemical Structure
Thumb
Synonyms
  1. 1,1,1-Trichloroethylene
  2. 1,1,2-Trichloroethene
  3. 1,1,2-Trichloroethylene
  4. 1,1-Dichloro-2-chloroethylene
  5. 1,2,2-Trichloroethylene
  6. 1-Chloro-2,2-dichloroethylene
  7. Acetylene trichloride
  8. Algylen
  9. Altene DG
  10. Anamenth
  11. Benzinol
  12. Blacosolv
  13. Blancosolv
  14. Cecolene
  15. Chlorilen
  16. Chlorylea
  17. Chlorylen
  18. Chorylen
  19. Circosolv
  20. Crawhaspol
  21. Densi nfluat
  22. Densinfluat
  23. Disparit b
  24. Distillex DS2
  25. Dukeron
  26. 1,1,2-Trichloro-Ethene
  27. Ethinyl trichloride
  28. Ethylene trichloride
  29. Fleck-flip
  30. Flock flip
  31. Fluate
  32. Gemalgene
  33. Germalgene
  34. Lanadin
  35. Lethurin
  36. Narcogen
  37. Narkogen
  38. Narkosoid
  39. Nialk
  40. Perm-a-chlor
  41. Perm-a-clor
  42. Petzinol
  43. Philex
  44. Tce (chlorohydrocarbon)
  45. Threthylen
  46. Threthylene
  47. Trethylene
  48. Tri-clene
  49. Tri-plus
  50. Tri-plus m
  51. Triad
  52. Trial
  53. Triasol
  54. Trichlooretheen
  55. Trichlooretheen [dutch]
  56. Trichloorethyleen, tri [dutch]
  57. Trichloraethen [german]
  58. Trichloraethylen
  59. Trichloraethylenum
  60. Trichloran
  61. Trichlorathane
  62. Trichloren
  63. Trichlorethene
  64. Trichlorethylene [french]
  65. Trichlorethylenum
  66. Trichloroethene
  67. Trichloroethylene (iupac)
  68. Trichloroethylene (tce)
  69. Trichloroethylene (with epichlorohydrin)
  70. Trichloroethylene [inn]
  71. Trichloroethylenum [inn-latin]
  72. Trichlorothene
  73. Triciene
  74. Tricloretene
  75. Tricloretene [italian]
  76. Tricloroetilene
  77. Tricloroetilene [dcit]
  78. Tricloroetilene [italian]
  79. Tricloroetileno [inn-spanish]
  80. Trielene
  81. Trielin
  82. Trielina [italian]
  83. Trieline
  84. Trik lone
  85. Triklone
  86. Triklone n
  87. Trilen
  88. Trilene
  89. Trilene TE-141
  90. Triline
  91. Trimar
  92. Triol
  93. Vestrol
  94. Vitran
  95. Westrosol
Chemical Formula C2HCl3
Average Molecular Weight 131.388
Monoisotopic Molecular Weight 129.914383153
IUPAC Name
1,1,2-trichloroethene
Traditional IUPAC Name
trichloroethylene
CAS Registry Number 79-01-6
SMILES
ClC=C(Cl)Cl
InChI Identifier
InChI=1S/C2HCl3/c3-1-2(4)5/h1H
InChI Key InChIKey=XSTXAVWGXDQKEL-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Organic Halides
Class Organochlorides
Sub Class Not Available
Direct Parent Organochlorides
Alternative Parents
  • Acyclic Alkenes
Molecular Framework Aliphatic Acyclic Compounds
Substituents Not Available
External Descriptors
  • chloroethenes(ChEBI)
  • a small molecule(Cyc)
Biological Properties
Status Not Available
Origin Not Available
Cellular Locations Not Available
Biofluid Locations Not Available
Tissue Locations Not Available
Pathways Not Available
Physical Properties
State Not Available
Appearance Colorless liquid.
Experimental Properties
Property Value
Melting Point -84.7 C
Boiling Point Not Available
Solubility 1.28 mg/mL at 25 °C [HORVATH,AL et al. (1999)]
LogP Not Available
Predicted Properties
PropertyValueSource
water solubility1.96e+00 g/lALOGPS
logP2.45ALOGPS
logP2.18ChemAxon
logS-1.8ALOGPS
physiological charge0ChemAxon
hydrogen acceptor count0ChemAxon
hydrogen donor count0ChemAxon
polar surface area0ChemAxon
rotatable bond count0ChemAxon
refractivity35.18ChemAxon
polarizability9.59ChemAxon
Spectra
Spectra Not Available
Toxicity Profile
Route of Exposure Oral (L14) ; inhalation (L14)
Mechanism of Action The toxic and carcinogenic effects of trichloroethylene are believed to be caused mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase, while chloral hydrate inhibits alcohol dehydrogenase. Studies in rodents have shown that neurotoxic effects may be caused by trichloroethylene's incorporation into brain membranes or ability to alter the fatty acid pattern of brain phospholipids and amino acids. One of the mechanisms of trichloroethylene's carcinogenicity is believed to be the peroxisome proliferation induced by its metabolites. (L14, T12, A46)
Metabolism Trichloroethylene is absorbed into the bloodstream and rapidly distributed throughout the body. Some is metabolized via cytochrome P-450 enzymes and the glutathione-conjugation pathway into metabolites such as trichloroacetic acid and trichloroethanol, which are excreted primarily in the urine. However, most trichoroethylene is exhaled unchanged or as carbon dioxide. (L15)
Toxicity Values LD50: 2402 mg/kg (Oral, Mouse) (T18) LD50: 20 001 mg/kg (Dermal, Rabbit) (T18) LD50: 3222 mg/kg (Intraperitoneal, Mouse) (T18)
Lethal Dose 3 to 5 mg/kg for an adult human. (L138)
Carcinogenicity (IARC Classification) 2A, probably carcinogenic to humans. (L135)
Uses/Sources Trichloroethylene is mainly used as an industrial solvent, particularily to remove grease from metal parts. It is also an ingredient in adhesives, paint removers, typewriter correction fluids, and spot removers. Exposure may result from contact with contaminated water. (L14)
Minimum Risk Level Acute Inhalation: 2 ppm (L134) Intermediate Inhalation: 0.1 ppm (L134) Acute Oral: 0.2 mg/kg/day (L134)
Health Effects Chronic inhalation or ingestion of tricholoethylene causes nerve, kidney, and liver damage, impaired immune system function, impaired fetal development in pregnant women, and possibly death. It has also been linked to both kidney and liver cancer. (L14)
Symptoms Inhalation of trichloroethylene causes headaches, lung irritation, dizziness, poor coordination, and difficulty concentrating, while ingestion results in nausea. Larger amounts may cause unconciousness and impaired heart function. Skin contact often results in rashes. (L14)
Treatment There is no known antidote for trichloroethylene. Exposure is usually handled with symptomatic treatment. (L15)
Normal Concentrations
Not Available
DrugBank ID Not Available
HMDB ID Not Available
PubChem Compound ID 6575
KEGG ID C06790
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 16602
BioCyc ID TRICHLOROETHENE
CTD ID D014241
Stitch ID Trichloroethylene
PDB ID Not Available
ACToR ID 1414
Wikipedia Link http://en.wikipedia.org/wiki/Trichloroethylene
References
General References
  • A46 — Cummings BS, Parker JC, Lash LH: Role of cytochrome P450 and glutathione S-transferase alpha in the metabolism and cytotoxicity of trichloroethylene in rat kidney. Biochem Pharmacol. 2000 Mar 1;59(5):531-43. [10660119 ]
  • A50 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]
  • T12 — Committee on Human Health Risks of Trichloroethylene, National Research Council (2006). Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues. Washington, DC: National Academies Press.
  • T18 — Hayes WJ Jr. and Laws ER Jr. (eds) (1991). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc.
  • L14 — ATSDR - Agency for Toxic Substances and Disease Registry (1997). Toxicological profile for trichloroethylene. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  • L15 — CCOHS - Canadian Centre for Occupational Health & Safety (1998). Trichloroethylene. [Link]
  • L134 — ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  • L135 — International Agency for Research on Cancer (2009). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  • L138 — HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). [Link]

Targets

1. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial

Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (A50)
UniProt ID: Q15118
Gene: PDK1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A50 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

2. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial

Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (A50)
UniProt ID: Q15119
Gene: PDK2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A50 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

3. Alcohol dehydrogenase 1A

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P07327
Gene: ADH1A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

4. Alcohol dehydrogenase 1B

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P00325
Gene: ADH1B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

5. Alcohol dehydrogenase 1C

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P00326
Gene: ADH1C
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

6. Alcohol dehydrogenase class 4 mu/sigma chain

Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P40394
Gene: ADH7
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

7. Alcohol dehydrogenase class-3

Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P11766
Gene: ADH5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

8. Alcohol dehydrogenase 4

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P08319
Gene: ADH4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

9. Alcohol dehydrogenase 6

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (A51)
UniProt ID: P28332
Gene: ADH6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A51 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

10. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 3, mitochondrial

Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (A50)
UniProt ID: Q15120
Gene: PDK3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A50 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

11. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial

Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (A50)
UniProt ID: Q16654
Gene: PDK4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A50 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

12. 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. (T10)
UniProt ID: P98194
Gene: ATP2C1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

13. 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. (T10)
UniProt ID: O75185
Gene: ATP2C2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P14867
Gene: GABRA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P47869
Gene: GABRA2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P34903
Gene: GABRA3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P48169
Gene: GABRA4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P31644
Gene: GABRA5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: Q16445
Gene: GABRA6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P18505
Gene: GABRB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P47870
Gene: GABRB2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P28472
Gene: GABRB3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: O14764
Gene: GABRD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P78334
Gene: GABRE
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: Q8N1C3
Gene: GABRG1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P18507
Gene: GABRG2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

27. 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. (T10)
UniProt ID: Q99928
Gene: GABRG3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

28. 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. (T10)
UniProt ID: O00591
Gene: GABRP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

29. 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. (T10)
UniProt ID: P24046
Gene: GABRR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

30. 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. (T10)
UniProt ID: P28476
Gene: GABRR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

31. 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. (T10)
UniProt ID: A8MPY1
Gene: GABRR3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

32. 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. (T10)
UniProt ID: Q9UN88
Gene: GABRQ
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

33. 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. (T10)
UniProt ID: P20020
Gene: ATP2B1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

34. 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. (T10)
UniProt ID: Q01814
Gene: ATP2B2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

35. 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. (T10)
UniProt ID: Q16720
Gene: ATP2B3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

36. 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. (T10)
UniProt ID: P23634
Gene: ATP2B4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

37. 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. (T10)
UniProt ID: O14983
Gene: ATP2A1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

38. 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. (T10)
UniProt ID: P16615
Gene: ATP2A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

39. 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. (T10)
UniProt ID: Q93084
Gene: ATP2A3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P54710
Gene: FXYD2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — 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 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. (T10)
UniProt ID: P05023
Gene: ATP1A1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

42. 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. (T10)
UniProt ID: P50993
Gene: ATP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

43. 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. (T10)
UniProt ID: P13637
Gene: ATP1A3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

44. 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. (T10)
UniProt ID: Q13733
Gene: ATP1A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

45. 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. (T10)
UniProt ID: P05026
Gene: ATP1B1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

46. 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. (T10)
UniProt ID: P14415
Gene: ATP1B2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

47. 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. (T10)
UniProt ID: P54709
Gene: ATP1B3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T10 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

48. 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. (T152)
UniProt ID: P03372
Gene: ESR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T152 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.

49. 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. (T152)
UniProt ID: Q92731
Gene: ESR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T152 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.