Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: This toxin potently blocks acid-sensing ion channel ASIC3 homotrimers and heterotrimers containing ASIC3 (composed with isoforms of ASIC1 and ASIC2) (PubMed:15044953). It also weakly inhibits potassium channels, and sodium channels (PubMed:15044953, PubMed:21943094, PubMed:22972919, PubMed:25337890). On homomeric ASIC3, this protein shows IC(50)=57-87 nM on rat, 37.3 nM on mouse and 175 nM on human channels (PubMed:15044953, PubMed:18923424, PubMed:19306891, PubMed:20813121, PubMed:21943094, PubMed:22851922, PubMed:22851929). The blockade is rapid and reversible (PubMed:15044953). On heterotrimeric forms, the toxin is less potent (IC(50)=117 nM on rat ASIC2b-ASIC3 channel, 900 nM on rat ASIC1b-ASIC3, and 2 uM on rat ASIC1a-ASIC3) (PubMed:15044953). It weakly inhibits Kv3.4/KCNC4 potassium channels (3 uM of the toxin inhibits 38% of Kv3.4 current) (PubMed:15044953). It reversibly and voltage-dependently inhibits hKv11.1/KCNH2/ERG1 potassium channels (IC(50)=1.21 uM), inhibiting both peak and tail currents without action on channel inactivation (PubMed:25337890). It weakly inhibits rNav1.2/SCN2A (EC(50)=114 nM), rNav1.6/SCN8A current (17% at 1 uM of the toxin) and Nav1.8/SCN10A (IC(50)=6.6 uM on human channels expressed in oocytes, EC(50)=55 nM on rat channels expressed in oocytes, and 2.6 uM on rat channels in DRG neurons) (PubMed:21943094, PubMed:22972919). It may act on sodium channels by binding at site 1 or close by, when the pore is in an open configuration (PubMed:22972919). In vivo, central injection does not induce neurotoxin symptoms in mice even after 24 hours (PubMed:15044953). However, it abolishes acid-induced pain in rats (PubMed:18923424). {ECO:0000269|PubMed:15044953, ECO:0000269|PubMed:18923424, ECO:0000269|PubMed:19306891, ECO:0000269|PubMed:20813121, ECO:0000269|PubMed:21943094, ECO:0000269|PubMed:22851922, ECO:0000269|PubMed:22851929, ECO:0000269|PubMed:22972919, ECO:0000269|PubMed:25337890}.
Target
voltage-gated sodium channel (Nav)
voltage-gated potassium channel (Kv)
proton-gated sodium channel / ASIC
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Anthopleura elegantissima (Green aggregating anemone) (Actinia elegantissima)
Neurotoxin
Ion channel impairing toxin
Potassium channel impairing toxin
Proton-gated sodium channel impairing toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin
This toxin potently blocks acid-sensing ion channel ASIC3 homotrimers and heterotrimers containing ASIC3 (composed with isoforms of ASIC1 and ASIC2) (PubMed:15044953). It also weakly inhibits potassium channels, and sodium channels (PubMed:15044953, PubMed:21943094, PubMed:22972919, PubMed:25337890).
Pi-actitoxin-Ael2b (Pi-AITX-Ael2b) (Toxin APETx2)
sea anemone
Sea anemone type 3 (BDS) potassium channel toxin family
Evidence at protein level
3D-structure
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Nematocyst
Neurotoxin
Pharmaceutical
Potassium channel impairing toxin
Proton-gated sodium channel impairing toxin
Secreted
Toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin