Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Remarkably non-selective toxin, with activity on many different ion channels (PubMed:29684594, PubMed:35200676). Weakly and reversibly inhibits rat and human homomeric ASIC1 (isoform ASIC1a) (IC(50)=4.8 uM, and IC(50)=14.6 uM), and ASIC3 (IC(50)=15.9 uM) (By similarity) (PubMed:29684594). Molecular modeling interaction with ASIC1a suggests that this peptide hinders the collapse of acidic pockets and stabilizes nonconducting channels state (PubMed:32326130). It activates several potassium channels including Kv1.1/KCNA1, Kv1.2/KCNA2, and drosophila Shaker IR (PubMed:35200676). It moderately to potently inhibits potassium channels including Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6, Kv2.1/KCNB1, Kv4.2/KCND2, Kv7.1/KCNQ1, Kv7.2/Kv7.3 (KCNQ2/KCNQ3), Kv7.4/KCNQ4, hERG/KCNH2, and C.elegans QKT1 (PubMed:35200676). On sodium channels, it moderately to potently inhibits Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A, Nav1.8/SCN10A, and B.germanica BgNav (PubMed:35200676). It also moderately to potently inhibits Cav3.1/CACNA1G, Cav3.2/CACNA1H, and Cav3.3/CACNA1I (PubMed:35200676). Significant shifts in the voltage-current relationship are observed on Kv and Nav, depending on the channel isoform, whereas the toxin does not seem to modulate the voltage-sensor domains of Cav channels, acting mainly as a pore blocker (PubMed:35200676). Does not activate nicotinic acetylcholine receptors (nAChR), but potentiates ACh-elicited current of human alpha-7/CHRNA7 nAChR (By similarity). Is also able to bind T.californica muscle-type nAChRs (By similarity). In vivo, causes an excitatory effect in mice behavior (By similarity). Also shows antihyperalgesic and analgesic activity in the acid-induced muscle pain mice model, and weak anti-inflammatory effect in models of acute local inflammation (By similarity) (PubMed:29684594). {ECO:0000250|UniProtKB:C0HM68, ECO:0000269|PubMed:29684594, ECO:0000269|PubMed:32326130, ECO:0000269|PubMed:35200676}.
Target
nicotinic acetylcholine receptor (nAChR)
acetylcholine receptor
voltage-gated sodium channel (Nav)
voltage-gated potassium channel (Kv)
voltage-gated calcium channel (Cav)
proton-gated sodium channel / ASIC
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Radianthus crispa (Leathery sea anemone) (Heteractis crispa)
Neurotoxin
Calcium channel impairing toxin
Ion channel impairing toxin
Potassium channel impairing toxin
Proton-gated sodium channel impairing toxin
Voltage-gated calcium channel impairing toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin
Remarkably non-selective toxin, with activity on many different ion channels (PubMed:29684594, PubMed:35200676). Weakly and reversibly inhibits rat and human homomeric ASIC1 (isoform ASIC1a) (IC(50)=4.8 uM, and IC(50)=14.6 uM), and ASIC3 (IC(50)=15.9 uM) (By similarity) (PubMed:29684594).
Pi-stichotoxin-Hcr5b (Pi-SHTX-Hcr5b) (APETx-like peptide) (Hcr 1b-2)
sea anemone
Sea anemone type 3 (BDS) potassium channel toxin family
Evidence at protein level
Calcium channel impairing toxin
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Nematocyst
Neurotoxin
Potassium channel impairing toxin
Proton-gated sodium channel impairing toxin
Secreted
Toxin
Voltage-gated calcium channel impairing toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin