FEATURES

FAMILY

DESCRIPTION

Also known as 3SX2_DENPO, 3SX2. This three-finger toxin inhibits ASIC channels. It acts as a gating modifier toxin by decreasing the apparent proton sensitivity of activation and by slightly increasing the apparent proton sensitivity for inactivation (PubMed:24695733). It binds more tightly to the closed state and to a much lesser extent the inactivated/desensitized state of ASIC1a isoform of ASIC1 (PubMed:24695733). It interacts directly with the outside surface of the thumb domain of chicken ASIC1a (ASIC1a), but does not insert into the acidic pocket as suggested previously (By similarity). This binding leads to relocation of the thumb domain that could disrupt the acidic pocket of cASIC1a (By similarity). The peptide exerts both stimulatory and inhibitory effects on ASIC1a (PubMed:24695733). It reversibly inhibits rat ASIC1a (IC(50)=21-55 nM), rat ASIC1b (IC(50)=103-192 nM), rat ASIC1a-ASIC1b (IC(50)=72 nM), rat ASIC1a-ASIC2a (IC(50)=246-252 nM) and rat ASIC1a-ASIC2b (IC(50)=61 nM) (PubMed:23034652, PubMed:23624383, PubMed:24323786, PubMed:24695733, PubMed:26991634). In vivo, it shows a potent naloxone-resistant analgesic effect against acute and inflammatory pain upon central and peripheral injection (By similarity). In addition, it also has an opioid-independent effect on both thermal and mechanical inflammatory pain after systemic administration and is effective against neuropathic pain (By similarity).

EXTERNAL LINKS

3SX2

Mutations

Mutation(s) distribution

Mutations table