Record Information
Version2.0
Creation Date2009-07-03 22:19:04 UTC
Update Date2014-12-24 20:25:38 UTC
Accession NumberT3D2508
Identification
Common NameChlorotoxin
ClassProtein
DescriptionChlorotoxin is a peptide toxin produced by the Egyptian scorpion (Leiurus quinquestriatus quinquestriatus). It blocks small-conductance chloride channels. The fact that Chlorotoxin binds preferentially to glioma cells compared with non-neoplastic cells or normal brain cells has allowed the development of new methods for the treatment and diagnosis of several types of cancer. (3)
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Natural Compound
  • Organic Compound
  • Protein
  • Scorpion Toxin
Protein StructureT3d2508
Synonyms
Synonym
ClTx
CTX
Chemical FormulaNot Available
Average Molecular Mass4004.725 g/mol
CAS Registry Number163515-35-3
SequenceNot Available
Chemical Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Toxicity Profile
Route of ExposureInjection (sting/bite) (5)
Mechanism of ToxicityChlorotoxin blocks small conductance chloride channels. (3)
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases.
Toxicity ValuesLD50: 0.25 mg/kg (Subcutaneous, Mouse) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesChlorotoxin is a peptide toxin produced by the Egyptian scorpion (Leiurus quinquestriatus quinquestriatus). The fact that Chlorotoxin binds preferentially to glioma cells compared with non-neoplastic cells or normal brain cells has allowed the development of new methods for the treatment and diagnosis of several types of cancer. (3)
Minimum Risk LevelNot Available
Health EffectsChlorotoxin has been shown to cause paralysis in prey animals of the Egyptian scorpion. (3)
SymptomsScorpion stings cause tingling or burning at the site of the sting. In more severe cases, symptoms may include spasm in the throat, feeling of thick tongue, restlessness, muscular fibrillation, abdominal cramps, convulsions, incontinence, hypertension, hypotension, oliguria, cardiac arrhythmias, pulmonary edema, and respiratory failure. (1)
TreatmentAn antivenom exists for Leiurus quinquestriatus stings. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDP45639
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB ID1CHL
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D2508.pdf
General References
  1. Dreisbach, RH (1983). Handbook of Poisoning. Los Altos, California: Lange Medical Publications.
  2. Watt DD, Simard JM. Neurotoxic proteins in scorpion venom. J. Toxicol. Toxin Rev. 1984;3:181-221.
  3. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
  4. Wikipedia. Antivenom. Last Updated 1 July 2009. [Link]
  5. Wikipedia. Scorpion toxin. Last Updated 12 July 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.
Gene Name:
CLCN1
Uniprot ID:
P35523
Molecular Weight:
108625.435 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.
Gene Name:
CLCN2
Uniprot ID:
P51788
Molecular Weight:
98534.425 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
Gene Name:
CLCNKA
Uniprot ID:
P51800
Molecular Weight:
75284.08 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
Gene Name:
CLCNKB
Uniprot ID:
P51801
Molecular Weight:
75445.3 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated ion channel activity
Specific Function:
Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Involved in regulation of the cell cycle.
Gene Name:
CLIC1
Uniprot ID:
O00299
Molecular Weight:
26922.47 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated ion channel activity
Specific Function:
Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Modulates the activity of RYR2 and inhibits calcium influx.
Gene Name:
CLIC2
Uniprot ID:
O15247
Molecular Weight:
28356.1 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated ion channel activity
Specific Function:
Can insert into membranes and form chloride ion channels. May participate in cellular growth control.
Gene Name:
CLIC3
Uniprot ID:
O95833
Molecular Weight:
26648.135 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated ion channel activity
Specific Function:
Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3. Has alternate cellular functions like a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. Could also promote endothelial cell proliferation and regulate endothelial morphogenesis (tubulogenesis).
Gene Name:
CLIC4
Uniprot ID:
Q9Y696
Molecular Weight:
28771.8 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated ion channel activity
Specific Function:
Required for normal hearing (PubMed:24781754). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti (By similarity). Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. May play a role in the regulation of transepithelial ion absorption and secretion. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture (PubMed:15184393, PubMed:18028448, PubMed:20335315).
Gene Name:
CLIC5
Uniprot ID:
Q9NZA1
Molecular Weight:
46502.195 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated ion channel activity
Specific Function:
May insert into membranes and form chloride ion channels. May play a critical role in water-secreting cells, possibly through the regulation of chloride ion transport (By similarity).
Gene Name:
CLIC6
Uniprot ID:
Q96NY7
Molecular Weight:
73010.875 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Chloride transport protein, initially identified as voltage-gated chloride channel. The presence of the conserved gating glutamate residues suggests that is functions as antiporter.
Gene Name:
CLCN6
Uniprot ID:
P51797
Molecular Weight:
97287.84 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Volume-sensitive chloride channel activity
Specific Function:
Mediates the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the endosome and synaptic vesicle lumen, and may thereby affect vesicle trafficking and exocytosis. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory.
Gene Name:
CLCN3
Uniprot ID:
P51790
Molecular Weight:
90965.275 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons.
Gene Name:
CLCN4
Uniprot ID:
P51793
Molecular Weight:
84915.965 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.
Gene Name:
CLCN5
Uniprot ID:
P51795
Molecular Weight:
83146.045 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Slowly voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the lysosome lumen.
Gene Name:
CLCN7
Uniprot ID:
P51798
Molecular Weight:
88678.26 Da
References
  1. Wikipedia. Chlorotoxin. Last Updated 3 June 2009. [Link]