Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Potent and selective inhibitor of hNav1.7/SCN9A (IC(50)=610 nM) (PubMed:29393892). Also shows a weak activity towards Nav1.3/SCN3A (IC(50)=7950 nM) (PubMed:29393892). In addition, inhibits voltage-gated potassium channels (Kv) in rat DRG neurons (PubMed:18581053). It does not alter the voltage dependence of activation, but it causes a small hyperpolarizing shift in the steady-state inactivations of Nav1.7/SNC9A (PubMed:29393892). Chimera experiments show that the toxin binds to the DIIS3-S4 linker (site 4) of Nav1.7/SCN9A, whereas Nav1.7/SCN9A Asp-827 residue is shown by substitution experiments to be critical for its sensitivity (PubMed:19463735, PubMed:29393892). The toxin traps the domain II voltage sensor in the closed configuration, and not in an outward position (PubMed:29393892). In vivo, shows analgesic activity in three rodent pain models (formalin-induced, acid-induced, and thermal) (PubMed:29393892). {ECO:0000269|PubMed:18581053, ECO:0000269|PubMed:29393892, ECO:0000305|PubMed:19463735}.
Target
voltage-gated sodium channel (Nav)
voltage-gated potassium channel (Kv)
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Chilobrachys guangxiensis (Chinese earth tiger tarantula) (Chilobrachys jingzhao)
Neurotoxin
Ion channel impairing toxin
Potassium channel impairing toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin
Potent and selective inhibitor of hNav1.7/SCN9A (IC(50)=610 nM) (PubMed:29393892). Also shows a weak activity towards Nav1.3/SCN3A (IC(50)=7950 nM) (PubMed:29393892).
Mu-theraphotoxin-Cg1a (Mu-TRTX-Cg1a) (Jingzhaotoxin-34) (JZTX-34) (Peptide F6-25.51)
spider
Neurotoxin 10 (Hwtx-1) family, 39 (Jztx-34) subfamily
Evidence at protein level
3D-structure
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Knottin
Neurotoxin
Pharmaceutical
Potassium channel impairing toxin
Secreted
Signal
Toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:17476710}.