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Record Information
Version2.0
Creation Date2009-07-03 22:19:05 UTC
Update Date2014-12-24 20:25:38 UTC
Accession NumberT3D2512
Identification
Common NameIberiotoxin
ClassProtein
DescriptionIberiotoxin is a peptide toxin produced by the Eastern Indian red scorpion (Buthus tamulus). It selectively inhibits the current through large-conductance calcium-activated potassium channels. (2)
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Natural Compound
  • Organic Compound
  • Protein
  • Scorpion Toxin
Protein StructureT3d2512
Synonyms
Synonym
IbTx
Potassium channel toxin alpha-KTx 1.3
Chemical FormulaNot Available
Average Molecular Mass4253.920 g/mol
CAS Registry Number129203-60-7
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
  • Apical Membrane
  • Axoneme
  • Basolateral Membrane
  • Caveolae
  • Cell junction
  • Cell surface
  • Cytoskeleton
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Extracellular matrix
  • Membrane Fraction
  • Microtubule
  • Mitochondrial Membrane
  • Mitochondrion
  • Nuclear Membrane
  • Plasma Membrane
  • Sarcoplasmic Reticulum
  • Synaptic Vesicle
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
Circadian rhythmNot Availablemap04710
Pancreatic secretionNot Availablemap04972
Long-term potentiationNot Availablemap04720
Long-term depressionNot Availablemap04730
Insulin secretionNot Availablemap04911
EndocytosisNot Availablemap04144
EicosanoidsNot 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
SpectraNot Available
Toxicity Profile
Route of ExposureInjection (sting/bite) (3)
Mechanism of ToxicityIberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels with high affinity. It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel. (2)
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 ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIberiotoxin is a peptide toxin produced by the Eastern Indian red scorpion (Buthus tamulus). (2)
Minimum Risk LevelNot Available
Health EffectsIberiotoxin produces mainly cardiopulmonary abnormalities like circulatory derangements, myocarditis and changes in cardiac sarcolemmal ATPase. These abnormalities can potentially cause death. (2)
SymptomsIberiotoxin initially causes transient cholinergic stimulation (vomiting, profuse sweating, bradycardia, priapism, hypersalivation, and hypotension) which is followed by sustained adrenergic hyperactivity (hypertension, tachycardia, and myocardial failure). (1)
TreatmentTreatment is mainly symptomatic. Local pain is treated by injecting dehydroemetine at the site of the sting. Hypovolaemia is corrected by oral rehydration solution. Agitated, confused and non-cooperative patients are given a 5% dextrose saline drip. Patients with hypertension on admission are given a single dose of 5 mg sublingual nifedipine and oral prazosin. The blood pressure in patients with hypertension is controlled with sublingual nifedipine alone. Patients with pulmonary oedema are propped up and given intravenous aminophylline, sodium bicarbonate, oral prazosin, and oxygen by mask. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID71433880
ChEMBL IDNot Available
ChemSpider ID31149632
KEGG IDNot Available
UniProt IDP24663
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDIberiotoxin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D2512.pdf
General References
  1. Vidaud C, Dedieu A, Basset C, Plantevin S, Dany I, Pible O, Quemeneur E: Screening of human serum proteins for uranium binding. Chem Res Toxicol. 2005 Jun;18(6):946-53. [15962929 ]
  2. Wikipedia. Iberiotoxin. Last Updated 24 June 2009. [Link]
  3. Wikipedia. Scorpion toxin. Last Updated 12 July 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Wikipedia. Iberiotoxin. Last Updated 24 June 2009. [Link]
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. Wikipedia. Iberiotoxin. Last Updated 24 June 2009. [Link]
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. Wikipedia. Iberiotoxin. Last Updated 24 June 2009. [Link]
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. Wikipedia. Iberiotoxin. Last Updated 24 June 2009. [Link]
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. Wikipedia. Iberiotoxin. Last Updated 24 June 2009. [Link]