Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Toxin with different activities on acid-sensing ion channels (ASIC) and nicotinic acetylcholine receptors (By similarity) (PubMed:32326130). Is able to bind T.californica muscle-type nicotinic acetylcholine receptors (nAChR) (alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)), and human alpha-7/CHRNA7 nicotinic acetylcholine receptors (By similarity). Weakly and reversibly inhibits rat homomeric ASIC1 (isoform ASIC1a) (IC(50)=1.25 uM), while it potentiates rat homomeric ASIC3 (EC(50)=1.53 uM) (By similarity) (PubMed:29684594, PubMed:32326130). Rat ASIC1a current inhibition is not complete, and reaches a maximum of 86% inhibition (PubMed:32326130). On rat ASIC3, does not activate the channel itself, but produces a remarkable potentiation of the transient current resulting from the acidic pulse (PubMed:32326130). At the maximal applied concentration, it elicits responses that are twice as high as those produced by extracellular protons (PubMed:32326130). Surprisingly, shows a different activity on human ASIC3. On the truncated human ASIC3 (ASIC3-D20), the toxin weakly inhibits the channel (By similarity). Molecular modeling interaction with rat ASIC1a suggests that it hinders the collapse of acidic pockets and stabilizes nonconducting channels state (PubMed:32326130). In vivo, causes an anxiolytic effect on mouse behavior (By similarity). Also shows an analgesic activity in an acid-induced muscle pain model, and important anti-inflammatory effect in models of acute local inflammation (By similarity). {ECO:0000250|UniProtKB:P0DRI4, ECO:0000269|PubMed:29684594, ECO:0000269|PubMed:32326130}.
Target
nicotinic acetylcholine receptor (nAChR)
acetylcholine receptor
voltage-gated sodium channel (Nav)
proton-gated sodium channel / ASIC
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Radianthus crispa (Leathery sea anemone) (Heteractis crispa)
Neurotoxin
Postsynaptic neurotoxin
Acetylcholine receptor inhibiting toxin
Ion channel impairing toxin
Proton-gated sodium channel impairing toxin
Toxin with different activities on acid-sensing ion channels (ASIC) and nicotinic acetylcholine receptors (By similarity) (PubMed:32326130). Is able to bind T.californica muscle-type nicotinic acetylcholine receptors (nAChR) (alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)), and human alpha-7/CHRNA7 nicotinic acetylcholine receptors (By similarity).
Pi-stichotoxin-Hcr5d (Pi-SHTX-Hcr5d) (APETx-like peptide) (Hcr 1b-4)
sea anemone
Sea anemone type 3 (BDS) potassium channel toxin family
Evidence at protein level
Acetylcholine receptor inhibiting toxin
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Nematocyst
Neurotoxin
Postsynaptic neurotoxin
Proton-gated sodium channel impairing toxin
Secreted
Toxin