| 8.B.8 The α-KTx15 Scorpion Toxin (α-KTx15) Family
Discrepin is a scorpion peptide that blocks preferentially the I(A) currents of the voltage-dependent K(+) channel of rat cerebellum granular cells. It was isolated from the venom of the buthid scorpion Tityus discrepans and contains 38 amino acid residues with a pyroglutamic acid at the N-terminal site. Discrepin has the lowest sequence identity (approx. 50%) among the six members of the α-KTx15 sub-family of scorpion toxins (Romeo et al., 2008).
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This family belongs to the Defensin Superfamily.
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| References: |
Abbas, N., M. Belghazi, Y. Abdel-Mottaleb, J. Tytgat, P.E. Bougis, and M.F. Martin-Eauclaire. (2008). A new Kaliotoxin selective towards Kv1.3 and Kv1.2 but not Kv1.1 channels expressed in oocytes. Biochem. Biophys. Res. Commun. 376: 525-530.
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Huys, I., C.Q. Xu, C.Z. Wang, H. Vacher, M.F. Martin-Eauclaire, C.W. Chi, and J. Tytgat. (2004). BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents. Biochem. J. 378: 745-752.
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Luna-RamÃrez, K., A. Bartok, R. Restano-Cassulini, V. Quintero-Hernández, F.I. Coronas, J. Christensen, C.E. Wright, G. Panyi, and L.D. Possani. (2014). Structure, molecular modeling, and function of the novel potassium channel blocker urotoxin isolated from the venom of the Australian scorpion Urodacus yaschenkoi. Mol Pharmacol 86: 28-41.
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Place, A.R., J. Ramos-Franco, A.L. Waters, J. Peng, and M.T. Hamann. (2024). Sterolysin from a 1950s culture of Karlodinium veneficum (aka Gymnodinium veneficum Ballantine) forms lethal sterol dependent membrane pores. Sci Rep 14: 17998.
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Prochnicka-Chalufour, A., G. Corzo, H. Satake, M.F. Martin-Eauclaire, A.R. Murgia, G. Prestipino, G. D'Suze, L.D. Possani, and M. Delepierre. (2006). Solution structure of discrepin, a new K+ -channel blocking peptide from the α- KTx15 subfamily. Biochemistry. 45: 1795-1804.
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Romeo, S., G. Corzo, A. Vasile, H. Satake, G. Prestipino, and L.D. Possani. (2008). A positive charge at the N-terminal segment of Discrepin increases the blocking effect of K+ channels responsible for the I(A) currents in cerebellum granular cells. Biochim. Biophys. Acta. 1780: 750-755.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 8.B.8.1.1 | Discrepin (K+ channel toxin α-KTx15.6) (solution structure solved (2AXK_A); Prochnicka-Chalufour et al., 2006) | Scorpions | Discrepin of Tityus discrepans (P84777) |
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| 8.B.8.1.11 | K+ channel toxin, α-KTx3.12 of Androctonus amoreuxi (African fattail scorpion; Scorpio amoreuxi) of 38 aas. It is a potent inhibitor of voltage-dependent potassium channels, with a preference for Kv1.3/KCNA3 versus Kv1.2/KCNA2 (Abbas et al. 2008). Members of this family can also form lethal sterol-dependent membrane pores called sterolysins (Place et al. 2024). | | α-KTx3.12 of Androctonus amoreuxi (African fattail scorpion) (Scorpio amoreuxi) |
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| 8.B.8.1.2 | Tx3 toxin; active on A-type K+ and HERG currents (Huys et al., 2004) | Scorpions | Tx3 of Buthus (Mesobuthus) martensii (Q8I0L5) |
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| 8.B.8.1.3 | Margatoxin MgTx; Toxin Ce; K+ channel toxin α-KTx of 39 aas. Blocks Kv1.3/KCNA3 voltage-gated potassium channels of human T-lymphocytes but not Ca2+-activated K+ channel | Animals | MgTx of Centruroides elegans (bark scorpion) |
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| 8.B.8.1.4 | K+ channel toxin 2.11 of 39 aas; also called Toxin Ce4. | Animals | Ce4 of Centruroides elegans |
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| 8.B.8.1.5 | Matentoxin-1 of 59 aas. | Animals | Matentoxin-1 of Mesobuthus martensii |
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| 8.B.8.1.6 | Putative K+ channel inhibitor, αKTx30.3; SjKTx51 | Animals | KTx51 of Scorpiops jendeki |
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| 8.B.8.1.7 | Potassium channel toxin alpha-KTx 6.21; Urotoxin, of 62 aas. Blocker of voltage-gated potassium channels. It has
highest activity on human voltage-gated potassium channel Kv1.2/KCNA2
channels, with an IC50 of 160 pM, whereas its affinity for other channels tested was in the nanomolar range (Luna-Ramírez et al. 2014).
| | α-KTx 6.21 of Urodacus yaschenkoi (Inland robust scorpion) |
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| 8.B.8.1.8 | Potassium channel toxin alpha-KTx 6.11; male-specific potassium channel inhibitor IsTX of 63 aas and 1 N-terminal TMS. Blocks voltage-gated potassium channels Kv1.1/KCNA1 and Kv1.3/KCNA3. Causes paralysis to crickets. | | ITx 6.11 of Opisthacanthus madagascariensis (Scorpion) |
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| Examples: |
| TC# | Name | Organismal Type | Example |