Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Mu-conotoxin KIIIA-P1: mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks Nav1.2/SCN2A (IC(50)5-124 nM), Nav1.4/SCN4A (IC(50)=20-90 nM), and Nav1.7/SCN9A (IC(50)=290-413 nM) (PubMed:17724025, PubMed:19221510, PubMed:21652775, PubMed:21709136, PubMed:21781281, PubMed:23146020, PubMed:25658507, PubMed:35167877). It moderately blocks Nav1.1/SCN1A, and mNav1.6/SCN8A (PubMed:17724025, PubMed:21652775, PubMed:21709136, PubMed:21781281, PubMed:23146020, PubMed:25658507, PubMed:35167877). It also shows a very low activity on Nav1.3/SCN3A (PubMed:17724025, PubMed:21781281). This toxin binds a microsite within the pore different from the tetrodotoxin binding site 1 (tested on Nav1.2) (PubMed:19221510). The block is partial, with a residual current that can be completely blocked by TTX (PubMed:19221510). The toxin probably docks at a more superficial site in the outer vestibule of the channel than does TTX (PubMed:19221510). On rNav1.2/SCN2A, it produces a block that is only partially reversible. The block of Nav1.7 is modified when beta-subunits are coexpressed with the alpha subunit (PubMed:23146020). Hence, blocks of channels containing beta-1 and beta-3 subunits are more potent (compared to channels without beta subunits), whereas blocks of channels containing beta-2 and beta-4 subunits are less potent (compared to channels without beta subunits) (PubMed:23146020). {ECO:0000269|PubMed:15882064, ECO:0000269|PubMed:17724025, ECO:0000269|PubMed:18950653, ECO:0000269|PubMed:19221510, ECO:0000269|PubMed:21652775, ECO:0000269|PubMed:21709136, ECO:0000269|PubMed:21781281, ECO:0000269|PubMed:23146020, ECO:0000269|PubMed:25658507}.
FUNCTION: Mu-conotoxin KIIIA-P2: This toxin potently blocks Nav1.2/SCN2A (Kd=230 nM, IC(50)=1.37 uM) and Nav1.4/SCN4A (Kd=830 nM, IC(50)=2 uM). It also moderately blocks Nav1.7/SCN9A (Kd=1.57 uM, IC(50)=5.4 uM) (PubMed:23167564, PubMed:35167877). In addition, this toxin may also inhibit other sodium channels, as does Mu-conotoxin KIIIA-P1 (PubMed:23167564). {ECO:0000269|PubMed:23167564, ECO:0000269|PubMed:35167877}.
FUNCTION: Mu-conotoxin KIIIA-N: This toxin moderately blocks Nav1.2/SCN2A (IC(50)=875 nM), Nav1.4/SCN4A (IC(50)=472 nM), and Nav1.7/SCN9A (IC(50)=887 nM) (PubMed:35167877). {ECO:0000269|PubMed:35167877}.
FUNCTION: Mu-conotoxin KIIIB-P1: This toxin potently blocks Nav1.2/SCN2A (Kd=470 nM). In addition, this toxin may also inhibit other sodium channels, as does Mu-conotoxin KIIIA-P1. {ECO:0000269|PubMed:23167564}.
FUNCTION: Mu-conotoxin KIIIB-P2: This toxin potently blocks Nav1.2/SCN2A (Kd=26 nM). In addition, this toxin may also inhibit other sodium channels, as does Mu-conotoxin KIIIA-P1. {ECO:0000269|PubMed:23167564}.
Target
voltage-gated sodium channel (Nav)
proton-gated sodium channel / ASIC
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Conus kinoshitai (Kinoshita's cone)
Neurotoxin
Ion channel impairing toxin
Voltage-gated sodium channel impairing toxin
Mu-conotoxin KIIIA-P1: mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks Nav1.2/SCN2A (IC(50)5-124 nM), Nav1.4/SCN4A (IC(50)=20-90 nM), and Nav1.7/SCN9A (IC(50)=290-413 nM) (PubMed:17724025, PubMed:19221510, PubMed:21652775, PubMed:21709136, PubMed:21781281, PubMed:23146020, PubMed:25658507, PubMed:35167877).
Mu-conotoxin KIIIB [Cleaved into: Mu-conotoxin KIIIA]
cone snail
Conotoxin M superfamily
Evidence at transcript level
3D-structure
Amidation
Cleavage on pair of basic residues
Disulfide bond
Ion channel impairing toxin
Neurotoxin
Secreted
Toxin
Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305|PubMed:15882064}.