8.B.7 The Cl- Channel Peptide Inhibitor (GaTx1) Family

A 3.7-kDa peptide toxin, GaTx1, of 34aas, is a potent and reversible inhibitor of CFTR (TC#3.A.1.202.1), acting from the cytoplasmic side of the membrane. GaTx1 is the first peptide toxin identified that inhibits a chloride channel of known molecular identity. It exhibits high specificity, showing no effect on a panel of nine transport proteins, including Cl- and K+ channels and ABC transporters. GaTx1-mediated inhibition of CFTR channel activity is strongly state-dependent; both potency and efficacy are reduced under conditions of elevated [ATP], suggesting that GaTx1 may function as a non-competitive inhibitor of ATP-dependent channel gating.

This family belongs to the Defensin Superfamily.



Fuller, M.D., C.H. Thompson, Z.R. Zhang, C.S. Freeman, E. Schay, G. Szakács, E. Bakos, B. Sarkadi, D. McMaster, R.J. French, J. Pohl, J. Kubanek, and N.A. McCarty. (2007). State-dependent inhibition of cystic fibrosis transmembrane conductance regulator chloride channels by a novel peptide toxin. J. Biol. Chem. 282(52):37545-7555.


TC#NameOrganismal TypeExample

The scorpion venom gland toxin, GaTx1 (Fuller et al., 2007)


GaTx1 of Leiurus quinquestriatus hebraeus (P85066)


Chlorotoxin-like peptide of 34 aas


Chlorotoxin of Androctonus australis (Sahara scorpion)


Probable chloride channel blocker of 25 aas which blocks small-conductance chloride channels, Scx1.  Belongs to the short scorpion toxin family.


Scx1 of Parabuthus schlechteri (scorpion)


C14 hottentoxin Hj1a of 61 aas



Hj1a of Hottentotta judaicus


Putative chloride channel toxin of 70 aas, Tx357.


Tx357 of Buthus occitanus israelis (Common yellow scorpion)