Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Gating-modifier toxin that inhibits mammalian and insect voltage-gated sodium channels. It shifts the voltage dependence of channel activation to more positive voltages. It shows potent activity on Nav1.4/SCN4A (IC(50)=103 nM), Nav1.5/SCN5A (IC(50)=268 nM) and Para/DmNav1 (IC(50)=555 nM) and lower activities on Nav1.2/SCN2A (IC(50)=1447 nM) and Nav1.6/SCN8A (IC(50)=3504 nM) (PubMed:25352595). In addition, at a concentration of 1 uM, the toxin inhibits 90-100% of sodium current through Nav1.2/SCN2A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A and Para/DmNav1 channels, when the voltage of maximal activation of the channel in control conditions is applied (Ref.1). It binds to the S3-S4 helix-loop-helix motif in the voltage-sensing domain of repeat 1 (shown on hNav1.4/SCN4A) (PubMed:29636418). The toxin is amphiphilic and binds to both neutral and negatively charged lipid vesicles with high affinity (PubMed:25352595, PubMed:29636418). The hydrophobic face lies on the opposite side to the hydrophobic faces of classical gating modifiers (PubMed:25352595). {ECO:0000269|PubMed:25352595, ECO:0000269|Ref.1}.
Target
voltage-gated sodium channel (Nav)
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Heriaeus mellotteei (Crab spider) (Heriaeus oblongus)
Neurotoxin
Ion channel impairing toxin
Voltage-gated sodium channel impairing toxin
Gating-modifier toxin that inhibits mammalian and insect voltage-gated sodium channels. It shifts the voltage dependence of channel activation to more positive voltages.
Mu-thomitoxin-Hme1c (Mu-TMTX-Hme1c) (Neurotoxin Hm-3)
spider
Neurotoxin 07 (Beta/delta-agtx) family
Evidence at protein level
3D-structure
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Knottin
Neurotoxin
Secreted
Toxin
Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.