Tmic
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Record Information
Version2.0
Creation Date2009-06-18 17:03:34 UTC
Update Date2014-12-24 20:23:03 UTC
Accession NumberT3D1026
Identification
Common NamePhenothrin
ClassSmall Molecule
DescriptionPhenothrin, also called sumithrin, is a synthetic pyrethroid (type 1) that kills adult fleas and ticks. It has also been used to kill head lice in humans. d-phenothrin is used as a component of aerosol insecticides for domestic use. Phenothrin is often used with methoprene, an insect growth regulator that interrupts the insect's biological life cycle by killing the eggs. In 2005, the EPA required Hartz Mountain Industries to cancel uses of several flea and tick products containing phenothrin that were linked to a range of adverse reactions, including hair loss, salivation, tremors, and numerous deaths in cats and kittens. In the short term, the agreement called for new warning labels on the products. A pyrethroid is a synthetic chemical compound similar to the natural chemical pyrethrins produced by the flowers of pyrethrums (Chrysanthemum cinerariaefolium and C. coccineum). Pyrethroids are common in commercial products such as household insecticides and insect repellents. In the concentrations used in such products, they are generally harmless to human beings but can harm sensitive individuals. They are usually broken apart by sunlight and the atmosphere in one or two days, and do not significantly affect groundwater quality except for being toxic to fish. (9, 11)
Compound Type
  • Ester
  • Ether
  • Household Toxin
  • Organic Compound
  • Pesticide
  • Pyrethroid
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Cis-fenothrin
(+/-)-phenoxybenzyl-cis,trans-chrysanthemate
(-)-Trans-phenothrin
2,2-Dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester
3-Phenoxybenzyl (+-)-cis-trans-chrysanthemate
3-Phenoxybenzyl (1RS)-cis,trans-chrysanthemate
3-Phenoxybenzyl chrysanthemate
3-Phenoxybenzyl D-Z/E chrysanthemate
Anchimanaito 20S
Anvil
Caswell No. 652B
D-phenothrin
D-phenthrin (trans)
Delta-(cis-trans)-phenothrin
Fenothrin
Forte
Multicide 2154
Multicide Concentrate F-2271
phenothrin, (1R-cis)-isomer
phenothrin, (1R-trans)-isomer
phenothrin, (1S-cis)-isomer
phenothrin, (1S-trans)-isomer
Phenothrin, (cis-(+-))-isomer
Phenothrin, (trans-(+-))-isomer
Phenothrine
Phenoxybenzyl (1R)-cis/trans chrysanthemate
Phenoxybenzyl chrysanthemate
Phenoxybenzyl-d-z/e-chrysanthemate
Phenoxythrin
Phonothrin
Pibutin
S 2539 (pesticide)
Sumithrin
Sumitrin
Wellcide
Chemical FormulaC23H26O3
Average Molecular Mass350.451 g/mol
Monoisotopic Mass350.188 g/mol
CAS Registry Number26002-80-2
IUPAC Name(3-phenoxyphenyl)methyl 2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropane-1-carboxylate
Traditional Namephenothrin
SMILESCC(C)=CC1C(C(=O)OCC2=CC=CC(OC3=CC=CC=C3)=C2)C1(C)C
InChI IdentifierInChI=1S/C23H26O3/c1-16(2)13-20-21(23(20,3)4)22(24)25-15-17-9-8-12-19(14-17)26-18-10-6-5-7-11-18/h5-14,20-21H,15H2,1-4H3
InChI KeyInChIKey=SBNFWQZLDJGRLK-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrethroids. These are organic compounds similar to the pyrethrins. Some pyrethroids containing a chrysanthemic acid esterified with a cyclopentenone (pyrethrins), or with a phenoxybenzyl group.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acid esters
Direct ParentPyrethroids
Alternative Parents
Substituents
  • Pyrethroid skeleton
  • Diphenylether
  • Diaryl ether
  • Aromatic monoterpenoid
  • Benzyloxycarbonyl
  • Monocyclic monoterpenoid
  • Monoterpenoid
  • Phenoxy compound
  • Phenol ether
  • Monocyclic benzene moiety
  • Cyclopropanecarboxylic acid or derivatives
  • Benzenoid
  • Carboxylic acid ester
  • Ether
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Carbonyl group
  • Organic oxide
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceYellow to yellow-brown liquid (12).
Experimental Properties
PropertyValue
Melting Point< 25°C
Boiling Point>290°C
Solubility9.7e-06 mg/mL at 25°C [TOMLIN,C (1997); <9.7 ug/L]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.002 g/LALOGPS
logP6.42ALOGPS
logP5.57ChemAxon
logS-5.2ALOGPS
pKa (Strongest Basic)-7.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area35.53 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity103.84 m³·mol⁻¹ChemAxon
Polarizability39.83 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0409000000-29f91143368a5e163638View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-3935000000-1f5ba52cfd1331e3c829View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pvi-7900000000-a7c057d4e94614b05bf6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0109000000-2146ad06bc95b25bf442View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-2809000000-986cbdb101e42868e61bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9400000000-8f041a7fa0db67d9ea24View in MoNA
MSMass Spectrum (Electron Ionization)splash10-00e9-5900000000-82828ceb9c78ca715405View in MoNA
Toxicity Profile
Route of ExposureInhalation (10); oral (10); dermal (10) ; eye contact (10).
Mechanism of ToxicityBoth type I and type II pyrethroids exert their effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. They appear to bind to the membrane lipid phase in the immediate vicinity of the sodium channel, thus modifying the channel kinetics. This blocks the closing of the sodium gates in the nerves, and thus prolongs the return of the membrane potential to its resting state. The repetitive (sensory, motor) neuronal discharge and a prolonged negative afterpotential produces effects quite similar to those produced by DDT, leading to hyperactivity of the nervous system which can result in paralysis and/or death. Other mechanisms of action of pyrethroids include antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, and actions on calcium ions. They also inhibit calium channels and Ca2+, Mg2+-ATPase. (5, 6, 10)
Metabolismd-Phenothrin is a fast acting insecticide, effective by contact and stomach action. It is rapidly metabolized and excreted by humans and has low human toxicity. For both cis- and trans- isomers, the product was metabolized by hydrolysis, oxidation and conjugation and a large part of d-Phenothrin is excreted unchanged in the urine and the faeces. Following oral administration of the (1R)- trans - isomer, the urine is the major excretory route. The isomer is extensively metabolized to oxidative and conjugated derivatives of the hydrolysed ester. Oxidative and conjugated derivatives of the (1R)- cis -isomer are also observed but hydrolysis of the ester linkage is a minor metabolic pathway. With this isomer the faeces is the major excretory route. The metabolic profiles aree similar following dermal application, although the rates of excretion for each isomer showed some differences between the two routes of administration. The major metabolite is 3-phenoxybenzyl alcohol (PBalc). Smaller amounts of PBacid and trace amounts of 4'-OH-PBacid are also found. It is stable to storage in the dark; d-Phenothrin is relatively unstable to sunlight or ultra violet irradiation, or in alkaline media. (12, 3)
Toxicity ValuesLD50: > 5000 mg/kg (Oral, Rat) (3) LD50: 10 000 mg/kg (Dermal, Rat) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPyrethroids are used as insecticides. (10)
Minimum Risk LevelNot Available
Health EffectsPyrethroid effects typically include rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, prostration with coarse whole body tremor, elevated body temperature, coma, and death. Paresthesia, severe corneal damage, hypotension and tachycardia, associated with anaphylaxis, can also occur following pyrethriod poisoning. (10)
SymptomsFollowing oral exposure, severe fine tremor, marked reflex hyperexcitability, sympathetic activation can occur. Nausea, vomiting and abdominal pain commonly occur and develop following ingestion. Sudden bronchospasm, swelling of oral and laryngeal mucous membranes, and anaphylactoid reactions have been reported after inhalation. Hypersensitivity reactions characterized by pneumonitis, cough, dyspnea, wheezing, chest pain, and bronchospasm may occur too . Dermatitis is the main effect of a dermal exposure to phenothrin. (7)
TreatmentFollowing oral exposure, the treatment is symptomatic and supportive and includes monitoring for the development of hypersensitivity reactions with respiratory distress. Provide adequate airway management when needed. Gastric decontamination is usually not required unless the pyrethrin product is combined with a hydrocarbon. Following inhalation exposure, move patient to fresh air. monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. If the contamination occurs through dermal exposure, Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. Vitamin E topical application is highly effective in relieving parenthesis. (13)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID4767
ChEMBL IDCHEMBL1322884
ChemSpider ID4603
KEGG IDC14387
UniProt IDNot Available
OMIM ID
ChEBI ID34916
BioCyc IDNot Available
CTD IDC006166
Stitch IDPhenothrin
PDB IDNot Available
ACToR ID13208
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1026.pdf
General References
  1. Brody SA, Loriaux DL: Epidemic of gynecomastia among haitian refugees: exposure to an environmental antiandrogen. Endocr Pract. 2003 Sep-Oct;9(5):370-5. [14583418 ]
  2. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [18948380 ]
  3. Suruga K, Kitagawa M, Yasutake H, Takase S, Goda T: Diet-related variation in cellular retinol-binding protein type II gene expression in rat jejunum. Br J Nutr. 2005 Dec;94(6):890-5. [16351764 ]
  4. Leng G, Lewalter J, Rohrig B, Idel H: The influence of individual susceptibility in pyrethroid exposure. Toxicol Lett. 1999 Jun 30;107(1-3):123-30. [10414789 ]
  5. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
  6. Hayes WJ Jr. and Laws ER Jr. (eds) (1991). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc.
  7. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  8. WHO (1990). Environmental Health Criteria 96: Phenothrin.
  9. Wikipedia. Pyrethroid. Last Updated 8 June 2009. [Link]
  10. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  11. Wikipedia. Phenothrin. Last Updated 1 August 2009. [Link]
  12. International Programme on Chemical Safety (IPCS) INCHEM (1994). Pesticide Document for D-phenothrin. [Link]
  13. Wikipedia. Blister agent. Last Updated 24 May 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization.
Gene Name:
SCN11A
Uniprot ID:
Q9UI33
Molecular Weight:
204919.66 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN7A
Uniprot ID:
Q01118
Molecular Weight:
193491.605 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
Gene Name:
SCN8A
Uniprot ID:
Q9UQD0
Molecular Weight:
225278.005 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular Weight:
226370.175 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth.
Gene Name:
SCN1B
Uniprot ID:
Q07699
Molecular Weight:
24706.955 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).
Gene Name:
SCN2B
Uniprot ID:
O60939
Molecular Weight:
24325.69 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Gene Name:
SCN3B
Uniprot ID:
Q9NY72
Molecular Weight:
24702.08 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the suceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.
Gene Name:
SCN4B
Uniprot ID:
Q8IWT1
Molecular Weight:
24968.755 Da
References
  1. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. [15950969 ]
  2. Klaassen CD, Amdur MO, Doull J (eds) (1995). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for pyrethrins and pyrethroids. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Signal transducer activity
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
Gene Name:
ATP2C1
Uniprot ID:
P98194
Molecular Weight:
100576.42 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Gene Name:
ATP2C2
Uniprot ID:
O75185
Molecular Weight:
103186.475 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Protein homodimerization activity
Specific Function:
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A1
Uniprot ID:
O14983
Molecular Weight:
110251.36 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
S100 protein binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.
Gene Name:
ATP2A2
Uniprot ID:
P16615
Molecular Weight:
114755.765 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A3
Uniprot ID:
Q93084
Molecular Weight:
113976.23 Da
References
  1. Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.64 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.49 uMOT_SRC1_SRC1FXR_1440Odyssey Thera
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]