Charybdotoxin (T3D2507)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (10)XML
Targets (10)
Record Information
Version2.0
Creation Date2009-07-03 22:19:03 UTC
Update Date2014-12-24 20:25:38 UTC
Accession NumberT3D2507
Identification
Common NameCharybdotoxin
ClassProtein
DescriptionCharybdotoxin is a peptide toxin produced by the Yellow scorpion (Leiurus quinquestriatus hebraeus). It is a neurotoxin that blocks calcium-activated potassium channels.This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus. (3)
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Natural Compound
  • Organic Compound
  • Protein
  • Scorpion Toxin
Protein StructureT3d2507
Synonyms
Synonym
ChTX
ChTx-a
ChTX-Lq1
CTX
Potassium channel toxin alpha-KTx 1.1
Chemical FormulaNot Available
Average Molecular Mass6673.890 g/mol
CAS Registry Number95751-30-7
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 Locations
  • Actin Cytoskeleton
  • Actin Filament
  • Apical Membrane
  • Basolateral Membrane
  • Cell junction
  • Cell surface
  • Cytoskeleton
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Extracellular matrix
  • Microsome
  • Mitochondrial Matrix
  • Mitochondrial Membrane
  • Mitochondrion
  • Nerve Fiber
  • Peroxisome
  • Plasma Membrane
  • Sarcoplasmic Reticulum
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Insulin secretionNot Availablemap04911
Cell cycleNot Availablemap04110
EicosanoidsNot AvailableNot Available
Vascular smooth muscle contractionNot Availablemap04270
Rna polymeraseNot Availablemap03020
Pancreatic secretionNot Availablemap04972
Pentose Phosphate PathwaySMP00031 map00030
Oxidative phosphorylationNot Availablemap00190
Olfactory transductionNot Availablemap04740
Long-term potentiationNot Availablemap04720
Cyclooxygenase InhibitorsNot AvailableNot Available
Arachidonic Acid MetabolismSMP00075 map00590
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) (6)
Mechanism of ToxicityCharybdotoxin is a neurotoxin that blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability. (1, 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/SourcesCharybdotoxin is a peptide toxin produced by the Yellow scorpion (Leiurus quinquestriatus hebraeus). (3)
Minimum Risk LevelNot Available
Health EffectsStings from the Yellow scorpion are painful but not usually fatal. However, in some cases envenomation may cause anaphylaxis, a potentially life-threatening allergic reaction to the venom. (4)
SymptomsStings from the Yellow scorpion are painful but not usually fatal. (4)
TreatmentAn antivenom exists for Leiurus quinquestriatus stings. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID44134622
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDP13487
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDCharybdotoxin
PDB ID1BAH
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D2507.pdf
General References
  1. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  2. Watt DD, Simard JM. Neurotoxic proteins in scorpion venom. J. Toxicol. Toxin Rev. 1984;3:181-221.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
  4. Wikipedia. Deathstalker. Last Updated 29 June 2009. [Link]
  5. Wikipedia. Antivenom. Last Updated 1 July 2009. [Link]
  6. Wikipedia. Scorpion toxin. Last Updated 12 July 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. 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. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
2. Calcium-activated potassium channel subunit beta-1
General Function:
Potassium channel regulator activity
Specific Function:
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate.
Gene Name:
KCNMB1
Uniprot ID:
Q16558
Molecular Weight:
21797.27 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
3. Calcium-activated potassium channel subunit beta-2
General Function:
Potassium channel regulator activity
Specific Function:
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Acts as a negative regulator that confers rapid and complete inactivation of KCNMA1 channel complex. May participate in KCNMA1 inactivation in chromaffin cells of the adrenal gland or in hippocampal CA1 neurons.
Gene Name:
KCNMB2
Uniprot ID:
Q9Y691
Molecular Weight:
27129.37 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
4. Calcium-activated potassium channel subunit beta-3
General Function:
Potassium channel regulator activity
Specific Function:
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Alters the functional properties of the current expressed by the KCNMA1 channel. Isoform 2, isoform 3 and isoform 4 partially inactivate the current of KCNBMA. Isoform 4 induces a fast and incomplete inactivation of KCNMA1 channel that is detectable only at large depolarizations. In contrast, isoform 1 does not induce detectable inactivation of KCNMA1. Two or more subunits of KCNMB3 are required to block the KCNMA1 tetramer.
Gene Name:
KCNMB3
Uniprot ID:
Q9NPA1
Molecular Weight:
31603.26 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
5. Calcium-activated potassium channel subunit beta-4
General Function:
Potassium channel regulator activity
Specific Function:
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.
Gene Name:
KCNMB4
Uniprot ID:
Q86W47
Molecular Weight:
23948.465 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
6. Intermediate conductance calcium-activated potassium channel protein 4
General Function:
Protein phosphatase binding
Specific Function:
Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).
Gene Name:
KCNN4
Uniprot ID:
O15554
Molecular Weight:
47695.12 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
7. Potassium voltage-gated channel subfamily A member 3
General Function:
Voltage-gated ion channel activity
Specific Function:
Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
Gene Name:
KCNA3
Uniprot ID:
P22001
Molecular Weight:
63841.09 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
8. Small conductance calcium-activated potassium channel protein 1
General Function:
Small conductance calcium-activated potassium channel activity
Specific Function:
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin (By similarity).
Gene Name:
KCNN1
Uniprot ID:
Q92952
Molecular Weight:
59986.87 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
9. Small conductance calcium-activated potassium channel protein 2
General Function:
Small conductance calcium-activated potassium channel activity
Specific Function:
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
Gene Name:
KCNN2
Uniprot ID:
Q9H2S1
Molecular Weight:
63759.03 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]
Target Details
10. Small conductance calcium-activated potassium channel protein 3
General Function:
Small conductance calcium-activated potassium channel activity
Specific Function:
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
Gene Name:
KCNN3
Uniprot ID:
Q9UGI6
Molecular Weight:
82025.305 Da
References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Charybdotoxin. Last Updated 25 April 2009. [Link]