General Information of This Target
Target ID
BTDT10258
Target Name
Sodium channel protein type 10 subunit alpha
Target Bioclass
Transporter and channel
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N.A.
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Venom peptide Sh41 Effect . [1]
 Toxin Info    Venom peptide Sh42 Effect . [1]
 Toxin Info    Mu-sparatoxin-Hv2 Inhibition rate . [2]
 Toxin Info    Mu-thomitoxin-Hme1c Inhibition rate . [3], [4]
 Toxin Info    Mu-conotoxin BuIIIC Inhibition rate . [5], [6]
 Toxin Info    Toxin Aah4 Inhibition rate . [7], [8], [9], [10]
 Toxin Info    Delta-theraphotoxin-Hm1a Inhibition rate . [11], [12], [13], [14]
 Toxin Info    Mu-theraphotoxin-Pm1a Inhibition rate
21 %
[15]
 Toxin Info    Mu/delta-theraphotoxin-Pm2a Inhibition rate
22 %
[15]
 Toxin Info    Beta-theraphotoxin-Eo1a Effective concentration 50
894 nM
[16]
 Toxin Info    Delta/kappa-theraphotoxin-Pm1a Effective concentration 50
1.1 μM
[17]
 Toxin Info    Beta-theraphotoxin-Ps1a IC50
20 - 610 nM
[18], [19], [20]
 Toxin Info    Kappa-actitoxin-Ael2a IC50
92 nM
[21- 27]
 Toxin Info    MuO-conotoxin MfVIA IC50
96 - 529 nM
[28], [29]
 Toxin Info    Beta/omega-theraphotoxin-Tp2a IC50
146 nM
[30- 49]
 Toxin Info    Mu-theraphotoxin-Pspp1 IC50
>10 μM
[45- 52]
 Toxin Info    Toxin GTx1-15 IC50
0.068 - 12.2 μM
[19- 53]
 Toxin Info    Toxin GTx1-15 IC50
0.068 - 12.2 μM
[42- 54]
 Toxin Info    Beta/omega-theraphotoxin-Tp2a IC50
4.6 μM
[30- 49]
 Toxin Info    APETx2 IC50
6.6 μM
[24- 63]
References
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Ref 2 Purification and Characterization of a Novel Insecticidal Toxin, -sparatoxin-Hv2, from the Venom of the Spider Heteropoda venatoria. Toxins (Basel). 2018 Jun 7;10(6):233. doi: 10.3390/toxins10060233.
Ref 3 Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae. J Biol Chem. 2015 Jan 2;290(1):492-504. doi: 10.1074/jbc.M114.595678. Epub 2014 Oct 28.
Ref 4 Spider toxin inhibits gating pore currents underlying periodic paralysis. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4495-4500. doi: 10.1073/pnas.1720185115. Epub 2018 Apr 10.
Ref 5 Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus. Toxicon. 2009 Jan;53(1):90-8. doi: 10.1016/j.toxicon.2008.10.017. Epub 2008 Nov 20.
Ref 6 Design of bioactive peptides from naturally occurring -conotoxin structures. J Biol Chem. 2012 Sep 7;287(37):31382-92. doi: 10.1074/jbc.M112.375733. Epub 2012 Jul 6.
Ref 7 Evidence for a position-specific deletion as an evolutionary link between long- and short-chain scorpion toxins. FEBS Lett. 2001 Apr 13;494(3):246-8. doi: 10.1016/s0014-5793(01)02336-5.
Ref 8 The amino acid sequence of toxin IV from the Androctonus australis scorpion: differing effects of natural mutations in scorpion alpha-toxins on their antigenic and toxic properties. Nat Toxins. 1992;1(1):61-9. doi: 10.1002/nt.2620010112.
Ref 9 Large scale purification of toxins from the venom of the scorpion Androctonus australis Hector. Toxicon. 1986;24(11-12):1131-9. doi: 10.1016/0041-0101(86)90139-x.
Ref 10 AaHIV a sodium channel scorpion toxin inhibits the proliferation of DU145 prostate cancer cells. Biochem Biophys Res Commun. 2020 Jan 8;521(2):340-346. doi: 10.1016/j.bbrc.2019.10.115. Epub 2019 Oct 24.
Ref 11 Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Mol Pharmacol. 2002 Jul;62(1):48-57. doi: 10.1124/mol.62.1.48.
Ref 12 Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature. 2016 Jun 23;534(7608):494-9. doi: 10.1038/nature17976. Epub 2016 Jun 6.
Ref 13 A selective Na(V)1.1 activator with potential for treatment of Dravet syndrome epilepsy. Biochem Pharmacol. 2020 Nov;181:113991. doi: 10.1016/j.bcp.2020.113991. Epub 2020 Apr 23.
Ref 14 Selective Na(V)1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E8077-E8085. doi: 10.1073/pnas.1804764115. Epub 2018 Aug 3.
Ref 15 Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of Na(V)1.7. Biomedicines. 2020 Feb 19;8(2):37. doi: 10.3390/biomedicines8020037.
Ref 16 The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel Na(V)1.8 to Enhance Activation. Front Pharmacol. 2022 Jan 14;12:789570. doi: 10.3389/fphar.2021.789570. eCollection 2021.
Ref 17 Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider. Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2110932119. doi: 10.1073/pnas.2110932119.
Ref 18 Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes. Mol Pharmacol. 2006 Feb;69(2):419-29. doi: 10.1124/mol.105.015941. Epub 2005 Nov 2.
Ref 19 Gating modifier toxins isolated from spider venom: Modulation of voltage-gated sodium channels and the role of lipid membranes. J Biol Chem. 2018 Jun 8;293(23):9041-9052. doi: 10.1074/jbc.RA118.002553. Epub 2018 Apr 27.
Ref 20 Lengths of the C-Terminus and Interconnecting Loops Impact Stability of Spider-Derived Gating Modifier Toxins. Toxins (Basel). 2017 Aug 12;9(8):248. doi: 10.3390/toxins9080248.
Ref 21 APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels. Mol Pharmacol. 2003 Jul;64(1):59-69. doi: 10.1124/mol.64.1.59.
Ref 22 Species diversity and peptide toxins blocking selectivity of ether-a-go-go-related gene subfamily K+ channels in the central nervous system. Mol Pharmacol. 2006 May;69(5):1673-83. doi: 10.1124/mol.105.019729. Epub 2006 Feb 23.
Ref 23 APETx1 from sea anemone Anthopleura elegantissima is a gating modifier peptide toxin of the human ether-a-go-go- related potassium channel. Mol Pharmacol. 2007 Aug;72(2):259-68. doi: 10.1124/mol.107.035840. Epub 2007 May 1.
Ref 24 A natural point mutation changes both target selectivity and mechanism of action of sea anemone toxins. FASEB J. 2012 Dec;26(12):5141-51. doi: 10.1096/fj.12-218479. Epub 2012 Sep 12.
Ref 25 Development of a rational nomenclature for naming peptide and protein toxins from sea anemones. Toxicon. 2012 Sep 15;60(4):539-50. doi: 10.1016/j.toxicon.2012.05.020. Epub 2012 Jun 5.
Ref 26 Defensin-neurotoxin dyad in a basally branching metazoan sea anemone. FEBS J. 2017 Oct;284(19):3320-3338. doi: 10.1111/febs.14194. Epub 2017 Sep 6.
Ref 27 Solution structure of APETx1 from the sea anemone Anthopleura elegantissima: a new fold for an HERG toxin. Proteins. 2005 May 1;59(2):380-6. doi: 10.1002/prot.20425.
Ref 28 Isolation, characterization and total regioselective synthesis of the novel O-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels. Biochem Pharmacol. 2012 Aug 15;84(4):540-8. doi: 10.1016/j.bcp.2012.05.008. Epub 2012 May 16.
Ref 29 Development of a O-Conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Sodium Channel NaV1.8. J Biol Chem. 2016 May 27;291(22):11829-42. doi: 10.1074/jbc.M116.721662. Epub 2016 Mar 29.
Ref 30 Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry. 2002 Dec 17;41(50):14734-47. doi: 10.1021/bi026546a.
Ref 31 Differential phospholipid binding by site 3 and site 4 toxins. Implications for structural variability between voltage-sensitive sodium channel domains. J Biol Chem. 2005 Mar 25;280(12):11127-33. doi: 10.1074/jbc.M412552200. Epub 2005 Jan 4.
Ref 32 Molecular interactions of the gating modifier toxin ProTx-II with NaV 1.5: implied existence of a novel toxin binding site coupled to activation. J Biol Chem. 2007 Apr 27;282(17):12687-97. doi: 10.1074/jbc.M610462200. Epub 2007 Mar 5.
Ref 33 ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels. Toxicon. 2007 Feb;49(2):194-201. doi: 10.1016/j.toxicon.2006.09.014. Epub 2006 Sep 27.
Ref 34 Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II. Mol Pharmacol. 2008 Mar;73(3):1020-8. doi: 10.1124/mol.107.041046. Epub 2007 Dec 21.
Ref 35 ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Mol Pharmacol. 2008 Nov;74(5):1476-84. doi: 10.1124/mol.108.047670. Epub 2008 Aug 26.
Ref 36 Evidence for multiple effects of ProTxII on activation gating in Na(V)1.5. Toxicon. 2008 Sep 1;52(3):489-500. doi: 10.1016/j.toxicon.2008.06.023. Epub 2008 Jul 9.
Ref 37 The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation. Mol Pharmacol. 2010 Dec;78(6):1124-34. doi: 10.1124/mol.110.066332. Epub 2010 Sep 20.
Ref 38 Inhibition of the activation pathway of the T-type calcium channel Ca(V)3.1 by ProTxII. Toxicon. 2010 Sep 15;56(4):624-36. doi: 10.1016/j.toxicon.2010.06.009. Epub 2010 Jun 23.
Ref 39 Crystallographic insights into sodium-channel modulation by the 4 subunit. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):E5016-24. doi: 10.1073/pnas.1314557110. Epub 2013 Dec 2.
Ref 40 Block of T-type calcium channels by protoxins I and II. Mol Brain. 2014 May 9;7:36. doi: 10.1186/1756-6606-7-36.
Ref 41 High Proteolytic Resistance of Spider-Derived Inhibitor Cystine Knots. Int J Pept. 2015;2015:537508. doi: 10.1155/2015/537508. Epub 2015 Dec 30.
Ref 42 Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel. J Med Chem. 2015 Mar 12;58(5):2299-314. doi: 10.1021/jm501765v. Epub 2015 Feb 19.
Ref 43 Binary architecture of the Nav1.2-2 signaling complex. Elife. 2016 Feb 19;5:e10960. doi: 10.7554/eLife.10960.
Ref 44 Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor. Sci Rep. 2017 Jan 3;7:39662. doi: 10.1038/srep39662.
Ref 45 Chemical Synthesis, Proper Folding, Na(v) Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins (Basel). 2019 Jun 21;11(6):367. doi: 10.3390/toxins11060367.
Ref 46 Studies examining the relationship between the chemical structure of protoxin II and its activity on voltage gated sodium channels. J Med Chem. 2014 Aug 14;57(15):6623-31. doi: 10.1021/jm500687u. Epub 2014 Jul 24.
Ref 47 Interaction of Tarantula Venom Peptide ProTx-II with Lipid Membranes Is a Prerequisite for Its Inhibition of Human Voltage-gated Sodium Channel NaV1.7. J Biol Chem. 2016 Aug 12;291(33):17049-65. doi: 10.1074/jbc.M116.729095. Epub 2016 Jun 16.
Ref 48 Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin. Cell. 2019 Feb 7;176(4):702-715.e14. doi: 10.1016/j.cell.2018.12.018. Epub 2019 Jan 17.
Ref 49 Structures of human Na(v)1.7 channel in complex with auxiliary subunits and animal toxins. Science. 2019 Mar 22;363(6433):1303-1308. doi: 10.1126/science.aaw2493. Epub 2019 Feb 14.
Ref 50 Pharmacological characterisation of the highly Na(V)1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 Jan 20;7:40883. doi: 10.1038/srep40883.
Ref 51 Corrigendum: Pharmacological characterisation of the highly Na(V)1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 May 26;7:46816. doi: 10.1038/srep46816.
Ref 52 Evaluation of the Spider (Phlogiellus genus) Phlotoxin 1 and Synthetic Variants as Antinociceptive Drug Candidates. Toxins (Basel). 2019 Aug 22;11(9):484. doi: 10.3390/toxins11090484.
Ref 53 Characterization of voltage-dependent calcium channel blocking peptides from the venom of the tarantula Grammostola rosea. Toxicon. 2011 Sep 1;58(3):265-76. doi: 10.1016/j.toxicon.2011.06.006. Epub 2011 Jun 28.
Ref 54 Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain. Toxins (Basel). 2016 Mar 17;8(3):78. doi: 10.3390/toxins8030078.
Ref 55 A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J. 2004 Apr 7;23(7):1516-25. doi: 10.1038/sj.emboj.7600177. Epub 2004 Mar 25.
Ref 56 ASIC3, a sensor of acidic and primary inflammatory pain. EMBO J. 2008 Nov 19;27(22):3047-55. doi: 10.1038/emboj.2008.213. Epub 2008 Oct 16.
Ref 57 Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3. Toxicon. 2009 Jul;54(1):56-61. doi: 10.1016/j.toxicon.2009.03.014. Epub 2009 Mar 21.
Ref 58 Expression in Pichia pastoris and characterization of APETx2, a specific inhibitor of acid sensing ion channel 3. Toxicon. 2010 Dec;56(8):1388-97. doi: 10.1016/j.toxicon.2010.08.004. Epub 2010 Sep 9.
Ref 59 Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2. Br J Pharmacol. 2012 Apr;165(7):2167-77. doi: 10.1111/j.1476-5381.2011.01674.x.
Ref 60 Cyclisation increases the stability of the sea anemone peptide APETx2 but decreases its activity at acid-sensing ion channel 3. Mar Drugs. 2012 Jul;10(7):1511-1527. doi: 10.3390/md10071511. Epub 2012 Jul 16.
Ref 61 Functional expression in Escherichia coli of the disulfide-rich sea anemone peptide APETx2, a potent blocker of acid-sensing ion channel 3. Mar Drugs. 2012 Jul;10(7):1605-1618. doi: 10.3390/md10071605. Epub 2012 Jul 23.
Ref 62 Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels. Protein Sci. 2005 Aug;14(8):2003-10. doi: 10.1110/ps.051378905. Epub 2005 Jun 29.
Ref 63 Understanding the molecular basis of toxin promiscuity: the analgesic sea anemone peptide APETx2 interacts with acid-sensing ion channel 3 and hERG channels via overlapping pharmacophores. J Med Chem. 2014 Nov 13;57(21):9195-203. doi: 10.1021/jm501400p. Epub 2014 Nov 4.
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