Pyrethrin I (T3D1857)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (20)XML
Targets (20)
Record Information
Version2.0
Creation Date2009-06-23 20:53:49 UTC
Update Date2014-12-24 20:24:46 UTC
Accession NumberT3D1857
Identification
Common NamePyrethrin I
ClassSmall Molecule
DescriptionPyrethrin I is a natural organic compound also called pyrethrolone ester of chrysanthemummonocarboxylic acid. It consists of structurally related esters with a cyclopropane core and oxidizes to become inactivated. Pyrethrins are naturally-occurring compounds with insecticidal properties that are found in pyrethrum extract from certain chrysanthemum flowers. The pyrethrins are often used in household insecticides and products to control insects on pets or livestock. (10, 12, 13)
Compound Type
  • Ester
  • Ether
  • Food Toxin
  • Household Toxin
  • Natural Compound
  • Organic Compound
  • Pesticide
  • Pyrethrin
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(+)-pyrethronyl (+)-trans-chrysanthemate
Chrysanthemum monocarboxylic acid pyrethrolone ester
Piretrina 1
Pyrethrin I (pi)
Pyrethrins
Pyrethrolone, chrysanthemum monocarboxylic acid ester
Chemical FormulaC21H28O3
Average Molecular Mass328.445 g/mol
Monoisotopic Mass328.204 g/mol
CAS Registry Number121-21-1
IUPAC Name(1S)-2-methyl-4-oxo-3-[(2E)-penta-2,4-dien-1-yl]cyclopent-2-en-1-yl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropane-1-carboxylate
Traditional Namepyrethrin I
SMILESC=C\C=C\CC1=C(C)[C@@H](OC(=O)[C@H]2C(C)(C)[C@@H]2C=C(C)C)CC1=O
InChI IdentifierInChI=1S/C21H28O3/c1-7-8-9-10-15-14(4)18(12-17(15)22)24-20(23)19-16(11-13(2)3)21(19,5)6/h7-9,11,16,18-19H,1,10,12H2,2-6H3/b9-8+/t16-,18+,19+/m1/s1
InChI KeyInChIKey=ROVGZAWFACYCSP-WIURDZCKSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrethrins. These are pyrethroids with a structure based on a skeleton that is characterized by the presence of a chrysanthemic acid esterified with a cyclopentenone derivative.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acid esters
Direct ParentPyrethrins
Alternative Parents
Substituents
  • Pyrethrin-backbone
  • Monoterpenoid
  • Monocyclic monoterpenoid
  • Cyclopropanecarboxylic acid or derivatives
  • Cyclic ketone
  • Ketone
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceViscous liquid (2).
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling Point170°C at 1.00E-01 mm Hg
Solubility0.0002 mg/mL [TOMLIN,C (1997)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.008 g/LALOGPS
logP5.1ALOGPS
logP4.58ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)18.09ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.37 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity99.03 m³·mol⁻¹ChemAxon
Polarizability38.44 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01t9-1928000000-7a2d685faff834950a2f2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-5910000000-79f1373b45fa4243c9812016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ufr-9400000000-1181de3e085f97ba58092016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0309000000-d6765f1a025c9ec3c4b42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00b9-0913000000-9519a1423c22ecbd17ad2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05tb-2900000000-3613a236ee33eb410c002016-08-03View Spectrum
Toxicity Profile
Route of ExposureInhalation (11) ; oral (11) ; dermal (11) ; eye contact (11).
Mechanism of ToxicityPyrethrins 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. (10, 3)
MetabolismFollowing ingestion, pyrethrins are hydrolysed by various digestive enzymes in the gastro-intestinal tract. However, a small portion of the insecticidally active compounds or its derivatives are absorbed, as shown by their toxicity and their effect on the liver. Pyrethrins may also be absorbed following inhalation or dermal contact. They are rapidly distributed to most tissues, particularly to those with a high lipid content, and are concentrated in central and peripheral nervous tissues. Pyrethrins or their metabolites are not known to be stored in the body or to be excreted in the milk, but no study of the matter has employed modern methods. The major metabolic pathways for pyrethrins are hydrolysis of the central ester bond, oxidative attacks at several sites, and conjugation reactions, to produce a complex array of primary and secondary water-soluble metabolites that undergo urinary excretion. The principal metabolite of pyrethrin I has a carboxylgroup on the isobutenyl group of the acid moiety and a cis-4',5'-dihydroxypent-2'-en1'-yl group in the lcohol moiety. In addition, pyrethrin I suffers attack on the pentadienyl side chain, possibly forming a 4'-5'-epoxide that is a precursor of two isomeric diols. Esterification also occurs during the metabolism of pyrethrin I. Metabolism is believed to involve nonspecific microsomal carboxyesterases and microsomal mixed function oxidases, which are located in nearly all tissue types, with particularly high activities in the liver. Metabolites, such as chrysanthemummonocarboxylic acid, are excreted in the urine and faeces. (10, 12, 1).
Toxicity ValuesLD50: 2370 mg/kg (Oral, Rat) (6) LD50: 1030 mg/kg (Oral, Rat) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesBreathing in contaminated air; drinking contaminated water or eating contaminated foods; skin and eye exposure (10).
Minimum Risk LevelNot Available
Health EffectsPyrethrin 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 pyrethrin poisoning. (10)
SymptomsThe clinical manifestations of inhalation exposure to pyrethrins can be local or systemic. Localized reactions confined to the upper respiratory tract include rhinitis, sneezing, scratchy throat, oral mucosal edema, and even laryngeal mucosal edema. Localized reactions of the lower respiratory tract include cough, shortness of breath, wheezing, and chest pain. An asthmalike reaction occurs with acute exposures in sensitized patients. Hypersensitivity pneumonitis characterized by chest pain, cough, dyspnea, and bronchospasm may occur in an individual chronically exposed. Large amounts may cause nausea, vomiting, tinnitus, headache, and other central nervous system disturbances. (4)
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. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID6433154
ChEMBL IDNot Available
ChemSpider ID4938339
KEGG IDC07594
UniProt IDNot Available
OMIM ID
ChEBI ID27815
BioCyc IDNot Available
CTD IDC009119
Stitch IDPyrethrin I
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1857.pdf
General References
  1. Yamamoto I, Elliott M, Casida JE: The metabolic fate of pyrethrin I, pyrethrin II, and allethrin. Bull World Health Organ. 1971;44(1-3):347-8. [5315352 ]
  2. Maeda A, Maeda T, Imanishi Y, Golczak M, Moise AR, Palczewski K: Aberrant metabolites in mouse models of congenital blinding diseases: formation and storage of retinyl esters. Biochemistry. 2006 Apr 4;45(13):4210-9. [16566595 ]
  3. 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 ]
  4. Zhang M, Hu P, Krois CR, Kane MA, Napoli JL: Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null mouse. FASEB J. 2007 Sep;21(11):2886-96. Epub 2007 Apr 13. [17435174 ]
  5. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  6. Tomlin CDS (ed) (1994). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council.
  7. 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.
  8. Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J (1997). Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins.
  9. Lewis RJ Sr. (ed) (1997). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: Van Nostrand Rheinhold Co.
  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. International Occupational Safety and Health Information Centre (2005). Allethrin. [Link]
  12. International Programme on Chemical Safety (IPCS) INCHEM (1965). Summary of Evaluations Performed by the Joint FAO/WHO Meeting on Pesticide Residues for Pyrethrins. [Link]
  13. Wikipedia. Pyrethrins. Last Updated 30 July 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Calcium-transporting ATPase type 2C member 1
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. 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]
Target Details
2. Calcium-transporting ATPase type 2C member 2
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. 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]
Target Details
3. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
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. 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]
Target Details
4. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
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. 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]
Target Details
5. Sodium channel protein type 1 subunit alpha
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]
Target Details
6. Sodium channel protein type 10 subunit alpha
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]
Target Details
7. Sodium channel protein type 11 subunit alpha
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]
Target Details
8. Sodium channel protein type 2 subunit alpha
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]
Target Details
9. Sodium channel protein type 3 subunit alpha
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]
Target Details
10. Sodium channel protein type 4 subunit alpha
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]
Target Details
11. Sodium channel protein type 5 subunit alpha
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]
Target Details
12. Sodium channel protein type 7 subunit alpha
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]
Target Details
13. Sodium channel protein type 8 subunit alpha
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]
Target Details
14. Sodium channel protein type 9 subunit alpha
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]
Target Details
15. Sodium channel subunit beta-1
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]
Target Details
16. Sodium channel subunit beta-2
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]
Target Details
17. Sodium channel subunit beta-3
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]
Target Details
18. Sodium channel subunit beta-4
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]
Target Details
19. Calcium release-activated calcium channel protein 1
General Function:
Store-operated calcium channel activity
Specific Function:
Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1 (PubMed:16582901, PubMed:16645049, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:19249086, PubMed:23307288, PubMed:24351972, PubMed:24591628). CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT (PubMed:16582901).
Gene Name:
ORAI1
Uniprot ID:
Q96D31
Molecular Weight:
32668.1 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.
Target Details
20. Calcium-activated potassium channel subunit alpha-1
General Function:
Voltage-gated potassium channel activity
Specific Function:
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
Gene Name:
KCNMA1
Uniprot ID:
Q12791
Molecular Weight:
137558.115 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.