TIIIA (P01616) Protein Card

General Information
Name TIIIA
Alternative name(s) T3a
Organism Conus tulipa (tulip cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Notes Block tetrodotoxin sensitive (TTX-S) Na channels (Lewis et al 2007). Presumably interacts with site 1 in the Na channel pore, because TIIIA competes with saxitoxin (Lewis et al 2007).

Classification
Conopeptide class conotoxin
Gene superfamily M superfamily
Cysteine framework III
Pharmacological family mu conotoxin

Sequence
RHGCCKGOKGCSSRECROQHCC(nh2)
Modified residues
positionsymbolname
8O4-Hydroxyproline
18O4-Hydroxyproline
23nh2C-term amidation
Sequence evidence nucleic acid level
Average Mass 2457.79
Monoisotopic Mass 2455.97
Isoelectric Point 12.28
Extinction Coefficient [280nm] NA

Activity

IC50: Voltage-Gated Sodium Channels

TargetOrganismIC50Ref
Nav1.1R. norvegicus900nM+/-130Wilson,M.J. et al. (2011)
Nav1.2R. norvegicus40nMLewis,R.J. et al. (2007)
Nav1.3R. norvegicus7.9uM+/-1.2Wilson,M.J. et al. (2011)
Nav1.4R. norvegicus9nMLewis,R.J. et al. (2007)
Nav1.5R. norvegicus>10uMWilson,M.J. et al. (2011)
Nav1.6R. norvegicus25uM+/-3Wilson,M.J. et al. (2011)
Nav1.7R. norvegicus>10uMWilson,M.J. et al. (2011)

Kd: Voltage-Gated Sodium Channels

TargetOrganismKdRef
Nav1.1R. norvegicus900nM+/-80Zhang,M.M. et al. (2013)
(+NaVβ1)710nM+/-70Zhang,M.M. et al. (2013)
(+NaVβ2)1.7uM+/-0.1Zhang,M.M. et al. (2013)
(+NaVβ3)480nM+/-50Zhang,M.M. et al. (2013)
(+NaVβ4)1.66uM+/-0.16Zhang,M.M. et al. (2013)
Nav1.2R. norvegicus45nM+/-5Zhang,M.M. et al. (2013)
(+NaVβ1)39nM+/-8Zhang,M.M. et al. (2013)
(+NaVβ2)55nM+/-6Zhang,M.M. et al. (2013)
(+NaVβ3)15nM+/-2Zhang,M.M. et al. (2013)
(+NaVβ4)67nM+/-10Zhang,M.M. et al. (2013)
45nM+/-10Wilson,M.J. et al. (2011)
Nav1.4R. norvegicus5nM+/-2Wilson,M.J. et al. (2011)

Percentage inhibition: Voltage-Gated Sodium Channels

TargetOrganism% inhibitionConcentrationRef
Nav1.2R. norvegicus953uMLewis,R.J. et al. (2007)
Nav1.3R. norvegicus03uMLewis,R.J. et al. (2007)
Nav1.5H. sapiens03uMLewis,R.J. et al. (2007)
Nav1.7H. sapiens03uMLewis,R.J. et al. (2007)
Nav1.8H. sapiens03uMLewis,R.J. et al. (2007)

Synthetic variants
TIIIA[E15A,add23A,add24A]RHGCCKGOKGCSSRACROQHCCAA(nh2)
TIIIA[E15A,add23A,add24D]RHGCCKGOKGCSSRACROQHCCAD(nh2)
TIIIA[E15A,add23A,add24K]RHGCCKGOKGCSSRACROQHCCAK(nh2)
TIIIA[E15A,add23A]RHGCCKGOKGCSSRACROQHCCA(nh2)
TIIIA[E15A,add23D]RHGCCKGOKGCSSRACROQHCCD(nh2)
TIIIA[E15A,add23K]RHGCCKGOKGCSSRACROQHCCK(nh2)
TIIIA[E15A]RHGCCKGOKGCSSRACROQHCC(nh2)

References
Lewis,R.J., Schroeder,C.I., Ekberg,J., Nielsen,K.J., Loughnan,M., Thomas,L., Adams,D.A., Drinkwater,R., Adams,D.J. and Alewood,P.F. (2007) Isolation and structure-activity of mu-conotoxin TIIIA, a potent inhibitor of tetrodotoxin-sensitive voltage-gated sodium channels Mol. Pharmacol. 71:676-685
Wilson,M.J., Yoshikami,D., Azam,L., Gajewiak,J., Olivera,B.M., Bulaj,G. and Zhang,M.M. (2011) μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc. Natl. Acad. Sci. U.S.A. 108:10302-10307
Schroeder,C.I., Adams,D., Thomas,L., Alewood,P.F. and Lewis,R.J. (2012) N- and C-terminal extensions of μ-conotoxins increase potency and selectivity for neuronal sodium channels. Biopolymers 98:161-165

Internal links
Nucleic acids
Structure NMR solution structure of mu-conotoxin TIIIA

External links
UniProtKB/Swiss-Prot P0C350
Ncbi P0C350

Tools