SCOP classification[1]
ClassSmall proteins
FoldKnottins (small inhibitors, toxins, lectins)
Superfamilyomega toxin-like
FamilySpider toxins
ProteinHanatoxin (HaTx, HaTx1, HaTx2, κ-TRTX-Gr1a)

Hanatoxin is a toxin found in the venom of the Grammostola spatulata tarantula.[2] The toxin is mostly known for inhibiting the activation of voltage-gated potassium channels, most specifically Kv4.2 and Kv2.1, by raising its activation threshold. [3]


Hanatoxin is a spider toxin from the venom of Grammostola spatulata.


Hanatoxin is the common name for two 4.1 kDa protein toxins, HaTx1 and HaTx2, which are similar in structure. HaTx is a peptide consisting of the following 35 amino-acids:


where *** is Ser for HaTx1 and Ala for HaTx2. First discovered in 1995, the difference in amino-acids and structure compared to other toxins known at that time has made hanatoxin the founding member of a family of spider toxins which inhibit voltage-gated potassium channels by modifying the voltage-sensor.[2][4] Its amino-acid sequence is homologous to various other toxins, including SGTx1 (76%) and grammotoxin (43%), both of which have similar gating-modification properties as hanatoxin.[5]


Hanatoxin binds to several types of voltage-gated ion channels. While the affinity is the highest for the Kv2.1 and Kv4.2 channels, it has been shown that the toxin may also bind to α1A voltage-gated Ca2+ channels.[6] Hanatoxin binds to the S3-S4 link of K+ channel-subunits, specifically the S3b segment, [7][8] and may bind to multiple subunits in a single ion channel.[3]

Mode of action

Similar to α-scorpion toxins, Hanatoxin inhibits – but does not block – the activation of, primarily, voltage-gated potassium channels. The S3-S4 link, where hanatoxin binds, is important for voltage-sensing and gate activation. By binding to the S3b segment, the S3b segment is pushed to the N-terminus of the S4 segment, restricting movement and, therefore, requiring a higher depolarization for channel-activation.[9]


While the effects of hanatoxin on its own are not thoroughly studied, it is part of the venom of Grammostola spatulata, which is considered slightly venomous to humans. The tarantula venom causes localized pain, itching and burning and does not seem to have any long-term effects on humans.[10] However, it is possible to have an allergic reaction to the venom, which could cause anaphylaxis, breathing problems and chest pains. The venom is lethal to smaller animals like mice: 0.1 ml of the venom is lethal to mice within about 5 minutes.[11]


The bite of Grammostola spatulata should be treated as a regular puncture wound. Washing and cleaning of the area is required and, if the reaction to the poison is too extreme, hospitalization and / or specialized medication may be required. Recovery from the bite usually takes about a week.[12]

Therapeutic use

Due to its specificity for particular ion-channels, hanatoxin has been recognized as a candidate for therapeutic drug development. The potassium channels that hanatoxin inhibits have huge diversity and are involved in a number of functions such as regulation of heart rate, insulin injection and muscle contraction.[13] One of the most promising therapeutic uses of hanatoxin is treatment of type-2 diabetes, by helping the regulation of insulin secretion.[14] While HaTx1 has successfully been synthesized by fusion in E. coli bacteria, its yield is very low (~1%), limiting its pharmacological use.[5]


  1. ^ http://supfam.org/SUPERFAMILY/cgi-bin/search.cgi?search_field=hanatoxin, consulted 10th Oct. 2012.
  2. ^ a b Swartz, K.J.; MacKinnon, R. (1995). "An Inhibitor of the Kv2.1 Potassium Channel Isolated from the Venom of a Chilean Tarantula". Neuron. 15 (4): 941–949. doi:10.1016/0896-6273(95)90184-1. PMID 7576642. S2CID 11188679.
  3. ^ a b Swartz, K.J.; MacKinnon, R. (1997). "Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites". Neuron. 18 (4): 665–673. doi:10.1016/s0896-6273(00)80306-2. PMID 9136774. S2CID 17929074.
  4. ^ Takahashi, H. e.a. (2000). "Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: common surface features of gating modifier toxins". Journal of Molecular Biology. 297 (3): 771–780. doi:10.1006/jmbi.2000.3609. PMID 10731427.
  5. ^ a b Lee, C. e.a. (2004). "Solution Structure and Functional Characterization of SGTx1, a Modifier of Kv2.1 Channel Gating". Biochemistry. 43 (4): 890–897. doi:10.1021/bi0353373. PMID 14744131.
  6. ^ Li-Smerin, Y.; Swartz, K.J. (1998). "Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels". Proceedings of the National Academy of Sciences. 95 (15): 8585–8589. Bibcode:1998PNAS...95.8585L. doi:10.1073/pnas.95.15.8585. PMC 21119. PMID 9671721.
  7. ^ Gonzalez, C. e.a. (2000). "Modulation of the Shaker K(+) channel gating kinetics by the S3-S4 linker". Journal of General Physiology. 115 (2): 193–208. doi:10.1085/jgp.115.2.193. PMC 2217197. PMID 10653896.
  8. ^ Li-Smerin, Y.; Swartz, K.J. (2001). "Helical structure of the COOH terminus of S3 and its contribution to the gating modifier toxin receptor in voltage-gated ion channels". Journal of General Physiology. 117 (3): 205–218. doi:10.1085/jgp.117.3.205. PMC 2225613. PMID 11222625.
  9. ^ Huang, P.; Shiau, Y.; Lou, K. (2007). "The interaction of spider gating modifier peptides with voltage-gated potassium channels". Toxicon. 49 (2): 285–292. doi:10.1016/j.toxicon.2006.09.015. PMID 17113615.
  10. ^ http://www.t3db.org/toxins, consulted 9th Oct. 2012.
  11. ^ Escoubas, P.; Rash, L. (2004). "Review Tarantulas: eight-legged pharmacists and combinatorial chemists". Toxicon. 43 (5): 555–574. doi:10.1016/j.toxicon.2004.02.007. PMID 15066413.
  12. ^ Tintinalli, J. e.a. (2004). Tintinalli’s Emergency Medicine: A comprehensive Study Guide, 7e. New York, NY McGraw-Hill, Chapter 50, 205.
  13. ^ Escoubas, P.; Bosmans, F. (2007). "Spider peptide toxins as leads for drug development". Natural Product Reports. 2 (6): 1–13. doi:10.1517/17460441.2.6.823. PMID 23489000. S2CID 22614679.
  14. ^ Herrington, J. e.a. (2006). "Blockers of the Delayed-Rectifier Potassium Current in Pancreatic β-Cells Enhance Glucose-Dependent Insulin Secretion". Diabetes. 55 (4): 1034–1042. doi:10.2337/diabetes.55.04.06.db05-0788. PMID 16567526.