FEATURES

FAMILY

DESCRIPTION

Also known as TXPR2_THRPR, TXPR2. Gating-modifier toxin that targets voltage-gated sodium channels with a selective activity on Nav1.7/SCN9A (IC(50)=1-1.5 nM) (PubMed:25026046, PubMed:31234412). It inhibits both activation and inactivation (PubMed:20855463). For inhibition of activation, it is 100-fold more selective for Nav1.7/SCN9A (IC(50)=0.26-3) than for other sodium channels (Nav1.2/SCN2A (IC(50)=40-540 nM), Nav1.3/SCN3A (IC(50)=102 nM), Nav1.4/SCN4A (IC(50)=30-39 nM), Nav1.5/SCN5A (IC(50)=19-90 nM), Nav1.6/SCN8A (IC(50)=26 nM), and Nav1.8/SCN10A (IC(50)=146 nM)) (PubMed:12475222, PubMed:17087985, PubMed:18156314, PubMed:18728100, PubMed:20855463, PubMed:25658507, PubMed:27311819, PubMed:30661758). For inhibition of inactivation, it is 20-fold more potent in inhibiting inactivation on Nav1.7/SCN9A (IC(50)=250 nM) than other channels (about 4.6 uM for all channels) (PubMed:20855463). It also weakly inhibits Cav1.2/CACNA1C and Cav3.2/CACNA1H (29% block at 1 uM) (PubMed:17087985, PubMed:20600227, PubMed:24886690). It inhibits Nav1.7/SCN9A activation by interacting with DII and impairs Nav1.7/SCN9A inactivation by interacting with DIV (PubMed:20855463). It docks on top of the DII S3 helix Nav1.7/SCN9A (PubMed:30661758, PubMed:30765606). It is about 60-fold less active on Nav1.7/SCN9A at depolarized potential (0 mV; IC(50)=15 nM), compared to -120 mV potential (IC(50)=0.26 nM) (PubMed:30661758). This toxin binds to lipid membrane (PubMed:15632158, PubMed:27311819). This ability correlates with hNav1.7/SCN9A inhibition, showing that membrane binding is the first step in the inhibitory mechanism of this toxin (PubMed:27311819). It inhibits Nav1.2/SCN2A less potently when it is coexpressed with SCN2B or SCN4B than when it is expressed alone, showing that beta subunits (SCN2B and SCN4B) have a protective effect (PubMed:24297919, PubMed:26894959).

EXTERNAL LINKS

TXPR2

Beta/omega-theraphotoxin-Tp2a

TXPR2

Molecular Synopsis