TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*8.B.5.1.1









Processed protoxin-1 (ProTx1; ProTx-I) of 35 aas.  Inhibits voltage-gated calcium channels Cav3.1/CACNA1G, voltage-gated potassium channels Kv2.1/KCNB1 and all sodium channels tested (Nav1.2/SCN2A, Nav1.5/SCN5A, Nav1.7/SCN9A, and Nav1.8/SCN10A). Shifts the voltage-dependence of channel activation to more positive potentials. Most potent against Nav1.8/SCN10A (Middleton et al. 2002; Priest et al. 2007).  A hydrophobic patch on the ProTx-II surface anchors it at the cell surface in a position that optimizes interaction of the peptide with the binding site on the voltage sensor domain. Binding of ProTx-II to the lipid membrane is directly linked to its potency as a hNaV1.7 channel inhibitor (Henriques et al. 2016).

Eukaryota
Metazoa
ProTx1 of Thrixopelma pruriens (P83480)
*8.B.5.2.1









Protoxin-2 (ProTx2; ProTx-II)
Eukaryota
Metazoa
ProTx2 of Thrixopelma pruriens (P83476)
*8.B.5.2.2









κ-Sparatoxin-Hv1b or heteropodatoxin 2 of 30 aas;  Inhibitor of voltage-gated potassium channels of the Kv4/KCND family (Ramracheya et al. 2010). Inhibition of Kv4.3/KCND3 and Kv4.2/KCND2 is strongly voltage-dependent, while inhibition of Kv4.1/KCND1 shows less voltage-dependence. Its binding site may be near the potassium channel voltage sensor. Also blocks calcium channels.

Eukaryota
Metazoa
heteropda toxin 2 of Heteropoda venatoria (Brown huntsman spider) (Aranea venatoria)
*8.B.5.3.1









Vanillotoxin-1 (VaTx1) of Trinidad chevron tarantula (35 aas) (activates TRPV1 causing pain) (Cramer and McIntyre, 2008)
Eukaryota
Metazoa
VaTx1 of Psalmopoeus cambridgei (P0C244)
*8.B.5.3.2









Vanillotoxin-3 (VaTx3) (34 aas; 50% identical to VATx1) (activates TRPV1 causing pain) (Cramer and McIntyre, 2008)
Eukaryota
Metazoa
VaTx3 of Psalmopoeus cambridgei (P0C246)
*8.B.5.3.3









Heteroscodratoxin-1 (HMTx1) of the tarantula (35 aas) (blocks the voltage-gated K+ channels: Kv2.1 (KCNB1), Kv2.2 (KCNB2), Kv4.1 (KCND1), Kv4.2 (KCND2) and Kv4.3 (KCND3) causing convulsions and death in mice (Escoubas et al, 2002))
Eukaryota
Metazoa
HMTx1 of Heteroscodra maculata (P60992)
*8.B.5.3.4









Huwentoxin-5 (HwTx5) precursor (86 aas) (insecticidal neurotoxin, Knottin-type; Diao et al., 2003; Zhang et al., 2003)
Eukaryota
Metazoa
HwTx5 of Ornithoctonus huwena (P61104)
*8.B.5.3.5









Jingzhaotoxin-11 (JzTx11) precursor (86 aas) (Inhibits K+ and Na+ channels (e.g., Kv2.1, Kv4.1, Kv4.2, and Kv1.5)(Structure known: Liao et al., 2006))
Eukaryota
Metazoa
JzTx11 of Chilobrachys jingzhao (P0C247)
*8.B.5.3.6









Hantotoxin-1 (HATx1) (35 aas) (Inhibits K+ and Ca2+ channels, e.g., Kv2.1, Kv4.2 and Cav2.1); (Structure known: Takahashi et al., 2000)
Eukaryota
Metazoa
Hanatoxin-1 of Grammostola rosea (tarantula) (P56852)
*8.B.5.3.7









ω-grammotoxin, SIA. Blocks P/Q type voltage-dependent calcium channels, Cav2.1 (Ono et al., 2011).

Eukaryota
Metazoa
SIA of Grammostola rosea (P60590)
*8.B.5.3.8









K+ channel blocker, a gating modifier toxin that inhibits by binding to the voltage sensor domain (VSD) of various VIC superfamily members, VSTx1 of 62 aas and 1 TMS (Ozawa et al. 2015). Many spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state (Lau et al. 2016). The toxin interacts with residues in an aqueous cleft formed between the extracellular S1-S2 and S3-S4 loops of the VSD whilst maintaining lipid interactions in the gaps formed between the S1-S4 and S2-S3 helices. The resulting network of interactions increases the energetic barrier to the conformational changes required for channel gating, and this is the mechanism by which gating modifier toxins inhibit voltage-gated ion channels (Lau et al. 2016).

Eukaryota
Metazoa
VSTx1 of Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata)