Beta/Omega-Theraphotoxin-Tp2a (BETA/omega-TRTX-TP2A) Thrixopelma Pruriens Recombinant Protein

Function: Blocks both tetrodotoxin-sensitive and tetrodotoxin-resistant human voltage-gated sodium channels by shifting the voltage dependence of channel activation to more positive potentials. Inhibits Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A, Nav1.8/SCN10A. Is significantly more potent against Nav1.7/SCN9A than the other Nav channel subtypes. Has no significant effect on Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.5/KCNA5, and Kv2.1/KCNB1 channels. Also inhibits Cav1.2/CACNA1C and Cav3.1/CACNA1G channels with an IC50 around 100 nM. Does not bind to the pharmacologically defined Nav channel sites 3 or 4. Neutralization of gating charges in the voltage sensor (S4) of domain II of Nav1.2/SCN2A prevents the effect of the toxin on gating current. Thus, it has been suggested that the toxin acts by trapping the voltage sensor of Nav channel domain II in the resting state, impeding outward gating movement of the IIS4 transmembrane segment of the channel. Binds to phospholipids. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Subcellular location: Secreted Ref.1.

Tissue specificity: Expressed by the venom gland. Ref.1

Domain: The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.

Sequence similarities: Belongs to the phrixotoxin family.

Mass spectrometry: Molecular mass is 3827 Da from positions 1 - 30. Determined by ESI. Ref.1Molecular mass is 3827 Da from positions 1 - 30. Determined by MALDI. Ref.1