SmIIIA (P01662) Protein Card

General Information
Name SmIIIA
Alternative name(s) Sm3a
Organism Conus stercusmuscarum
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor SmIIIA precursor (1629)
Notes Block tetrodotoxin resistant (TTX-R) Na channels and the blockade is irreversible (West et al 2002). 10 μM rapidly blocks A-fiber and C-fiber action potentials in mouse sciatic nerve [Wilson,M.J., Zhang,M (2015)].

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

Sequence
ZRCCNGRRGCSSRWCRDHSRCC
Modified residues
positionsymbolname
1ZPyroglutamic acid
Sequence evidence nucleic acid level
Average Mass 2606.90
Monoisotopic Mass 2605.00
Isoelectric Point NA
Extinction Coefficient [280nm] NA

Activity

IC50: Voltage-Gated Sodium Channels

TargetOrganismIC50Ref
Nav1.5R. norvegicus1.3uM+/-0.25Wilson,M.J. et al. (2011)
Nav1.6R. norvegicus160nM+/-40Wilson,M.J. et al. (2011)
Nav1.7R. norvegicus1.3uM+/-0.23Wilson,M.J. et al. (2011)
Nav1.8R. norvegicus>10uMWilson,M.J. et al. (2011)

Kd: Voltage-Gated Sodium Channels

TargetOrganismKdRef
Nav1.1R. norvegicus3.8nM+/-1.3Wilson,M.J. et al. (2011)
(+NaVβ1)2.4nM+/-0.6Zhang,M.M. et al. (2013)
(+NaVβ2)70nM+/-10Zhang,M.M. et al. (2013)
(+NaVβ3)2.3nM+/-0.3Zhang,M.M. et al. (2013)
(+NaVβ4)300nM+/-80Zhang,M.M. et al. (2013)
3.8nM+/-0.4Zhang,M.M. et al. (2013)
Nav1.2R. norvegicus1.3nM+/-0.3Zhang,M.M. et al. (2013)
1.3nM+/-0.7Wilson,M.J. et al. (2011)
(+NaVβ4)7.5nM+/-0.8Zhang,M.M. et al. (2013)
(+NaVβ1)0.9nM+/-0.2Zhang,M.M. et al. (2013)
(+NaVβ2)3.0nM+/-0.5Zhang,M.M. et al. (2013)
(+NaVβ3)0.9nM+/-0.3Zhang,M.M. et al. (2013)
Nav1.3R. norvegicus35nM+/-14Wilson,M.J. et al. (2011)
Nav1.4R. norvegicus220pM+/-100Wilson,M.J. et al. (2011)
Nav1.6R. norvegicus(+NaVβ2)750nM+/-60Zhang,M.M. et al. (2013)
(+NaVβ4)14nM+/-3Zhang,M.M. et al. (2013)
(+NaVβ3)59nM+/-13Zhang,M.M. et al. (2013)
69nM+/-13Zhang,M.M. et al. (2013)
(+NaVβ1)46nM+/-3Zhang,M.M. et al. (2013)
Nav1.7R. norvegicus(+NaVβ3+β4)350nM+/-30Zhang,M.M. et al. (2013)
(+NaVβ3+β2)200nM+/-30Zhang,M.M. et al. (2013)
(+NaVβ4)1.17uM+/-0.08Zhang,M.M. et al. (2013)
(+NaVβ112)100nM+/-10Zhang,M.M. et al. (2013)
(+NaVβ1+β4)550nM+/-80Zhang,M.M. et al. (2013)
(+NaVβ1+β2)380nM+/-100Zhang,M.M. et al. (2013)
(+NaVβ211)1.20uM+/-0.22Zhang,M.M. et al. (2013)
260nM+/-50Zhang,M.M. et al. (2013)
(+NaVβ1)130nM+/-20Zhang,M.M. et al. (2013)
(+NaVβ2)1.50uM+/-0.22Zhang,M.M. et al. (2013)
(+NaVβ3)110nM+/-10Zhang,M.M. et al. (2013)

References
West,P.J., Bulaj,G., Garrett,J.E., Olivera,B.M. and Yoshikami,D. (2002) Mu-conotoxin SmIIIA, a potent inhibitor of tetrodotoxin-resistant sodium channels in amphibian sympathetic and sensory neurons Biochemistry 41:15388-15393
Keizer,D.W., West,P.J., Lee,E.F., Yoshikami,D., Olivera,B.M., Bulaj,G. and Norton,R.S. (2003) Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA J. Biol. Chem. 278:46805-46813
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
Zhang,M.M., Wilson,M.J., Azam,L., Gajewiak,J., Rivier,J.E., Bulaj,G., Olivera,B.M. and Yoshikami,D. (2013) Co-expression of Na(V)β subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking μ-conotoxins. Br. J. Pharmacol. 168:1597-1610
Wilson,M.J., Zhang,M.M., Gajewiak,J., Azam,L., Rivier,J.E., Olivera,B.M. and Yoshikami,D. (2015) Α- and β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO§-conotoxin GVIIJ. J. Neurophysiol. 113:2289-2301

Internal links
Protein Precursor SmIIIA precursor (1629)
Nucleic acids
Structure STRUCTURAL BASIS FOR TETRODOTOXIN-RESISTANT SODIUM CHANNEL BINDING BY MU-CONOTOXIN SMIIIA

External links
Ncbi 1Q2J_A

Tools