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Record Information
Creation Date2009-07-03 22:18:57 UTC
Update Date2014-12-24 20:25:36 UTC
Accession NumberT3D2492
Common NameHolocyclotoxin
DescriptionHolocyclotoxin or Holocyclotoxin I is a peptide toxin produced by the Australian paralysis tick (Ixodes holocyclus) (3). This tick has been responsible for 20 human fatalities from 1900 to 1945, and up to 100,000 domestic animal fatalities annually. The toxin has a novel 3D fold with three of its four disulfide bonds comprising an inhibitory cystine knot (ICK) motif. (2)
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Insect Toxin
  • Natural Compound
  • Organic Compound
  • Protein
Protein StructureT3d2492
Holocyclotoxin 1
Chemical FormulaNot Available
Average Molecular Mass7834.125 g/mol
CAS Registry Number88254-04-0
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
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
AppearanceClear solution.
Experimental Properties
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectrum TypeDescriptionSplash KeyView
Toxicity Profile
Route of ExposureInjection (sting/bite) (6)
Mechanism of ToxicityHolocyclotoxin produces paralysis by acting at the neuromuscular junction. (1)
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/SourcesHolocyclotoxin is a peptide toxin produced by the tick (Ixodes holocyclus). (3)
Minimum Risk LevelNot Available
Health EffectsHolocyclotoxin is a neurotoxin that produces tick paralysis. (5)
SymptomsTick paralysis causes symptoms within 2-7 days, beginning with weakness in both legs that progresses to paralysis. The paralysis ascends to trunk, arms, and head within hours and may lead to respiratory failure and death. The disease can present as acute ataxia without muscle weakness. (5)
TreatmentOnce the tick is removed, symptoms usually diminish rapidly. An antivenom also exists for tick poisoning. (4, 5)
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 IDQ5UB45
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Grattan-Smith PJ, Morris JG, Johnston HM, Yiannikas C, Malik R, Russell R, Ouvrier RA: Clinical and neurophysiological features of tick paralysis. Brain. 1997 Nov;120 ( Pt 11):1975-87. [9397015 ]
  2. Vink S, Daly NL, Steen N, Craik DJ, Alewood PF: Holocyclotoxin-1, a cystine knot toxin from Ixodes holocyclus. Toxicon. 2014 Nov;90:308-17. doi: 10.1016/j.toxicon.2014.08.068. Epub 2014 Aug 27. [25172536 ]
  3. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  4. Wikipedia. Antivenom. Last Updated 1 July 2009. [Link]
  5. Wikipedia. Tick paralysis. Last Updated 3 June 2009. [Link]
  6. Wikipedia. Insect toxins. Last Updated 19 February 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available