RegIIA (P00032) Protein Card

General Information
Name RegIIA
Alternative name(s) Reg2a
Organism Conus regius
Organism region Eastern Pacific
Organism diet vermivorous
Protein Type Wild type
Protein precursor RegIIA precursor (5529)

Classification
Conopeptide class conotoxin
Gene superfamily A superfamily
Cysteine framework I
Pharmacological family alpha conotoxin

Sequence
GCCSHPACNVNNPHIC(nh2)
Modified residues
positionsymbolname
17nh2C-term amidation
Sequence evidence protein level
Average Mass 1663.88
Monoisotopic Mass 1662.63
Isoelectric Point 8.42
Extinction Coefficient [280nm] NA

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α3β2H. sapiens132.4nM[109.8-159.7]1.550uM AChCuny,H. et al. (2016)
(α3[P198Q]rβ2)31.0 nM[25-38.4]1.8ACh (50 uM)Kompella,S.N. et al. (2015)
704.1 nM[502.9-985.9]1.2ACh (50 uM)Kompella,S.N. et al. (2015)
R. norvegicus(α3[E187D]β2)7.3 nM[5-10.8]1.7ACh (50 uM)Kompella,S.N. et al. (2015)
(α3[Q198P]β2)520.9 nM[400.2-678.1]0.8ACh (50 uM)Kompella,S.N. et al. (2015)
(α3[Q73G]+[V75A]β2)29.6 nM[23.9-36.7]2.3ACh (50 uM)Kompella,S.N. et al. (2015)
(α3β2[D165E])32.2 nM[26.5-39]1.7ACh (50 uM)Kompella,S.N. et al. (2015)
(α3β2[D73E])37.6 nM[29.4-48.1]1.4ACh (50 uM)Kompella,S.N. et al. (2015)
(α3[D97V]β2)28.3 nM[23.8-33.7]1.7ACh (50 uM)Kompella,S.N. et al. (2015)
10.7 nM[8.8-12.9]-1.1ACh (50 uM)Kompella,S.N. et al. (2015)
33nM+/-430uM AChFranco,A. et al. (2012)
(α3β2[I181V])39.2 nM[31.3-49]1.1ACh (50 uM)Kompella,S.N. et al. (2015)
α3β4H. sapiens45.6nM[31.5-65.9]0.9300uM AchCuny,H. et al. (2016)
52.1 nM[42.9-63.3]1.9ACh (50 uM)Kompella,S.N. et al. (2015)
R. norvegicus47.3 nM[39.5-56.6]-1.5ACh (50 uM)Kompella,S.N. et al. (2015)
97nM+/-2030uM AChFranco,A. et al. (2012)
α4β2R. norvegicus >1uM30uM AChFranco,A. et al. (2012)
α6/α3β4β3R. norvegicus147 nM[118.7-182.1]-1.4ACh (50 uM)Kompella,S.N. et al. (2015)
α7H. sapiens210 nM[170-270]1.2200 uM AchYu et al. (2018)
103nM+/-23200uM AChFranco,A. et al. (2012)
R. norvegicus41 nM[33-50]1.1200 uM AchYu et al. (2018)
61.2 nM[47.8-78.4]-1.2ACh (200 uM)Kompella,S.N. et al. (2015)
α9α10H. sapiens(human a9 rat a10)>1uM 30uM AChFranco,A. et al. (2012)

Synthetic variants
RegIIA[H14A]GCCSHPACNVNNPAIC(nh2)
RegIIA[H5D]GCCSDPACNVNNPHIC(nh2)
RegIIA[I15A]GCCSHPACNVNNPHAC(nh2)
RegIIA[N11A,N12A]GCCSHPACNVAAPHIC(nh2)
RegIIA[N11A]GCCSHPACNVANPHIC(nh2)
RegIIA[N11H]GCCSHPACNVHNPHIC(nh2)
RegIIA[N11R]GCCSHPACNVRNPHIC(nh2)
RegIIA[N11Y]GCCSHPACNVYNPHIC(nh2)
RegIIA[N12A]GCCSHPACNVNAPHIC(nh2)
RegIIA[N9A]GCCSHPACAVNNPHIC(nh2)
RegIIA[N9F]GCCSHPACFVNNPHIC(nh2)
RegIIA[N9R]GCCSHPACRVNNPHIC(nh2)
RegIIA[N9W]GCCSHPACWVNNPHIC(nh2)
RegIIA[N9Y]GCCSHPACYVNNPHIC(nh2)
RegIIA[P13A]GCCSHPACNVNNAHIC(nh2)
RegIIA[V10A]GCCSHPACNANNPHIC(nh2)
RegIIA[V10F]GCCSHPACNFNNPHIC(nh2)
RegIIA[V10Y]GCCSHPACNYNNPHIC(nh2)

References
Franco,A., Pisarewicz,K., Moller,C., Mora,D., Fields,G.B. and Mari,F. (2006) Hyperhydroxylation: a new strategy for neuronal targeting by venomous marine molluscs Prog. Mol. Subcell. Biol. 43:83
Cuny,H., Kompella,S.N., Tae,H.S., Yu,R. and Adams,D.J. (2016) Key Structural Determinants in the Agonist Binding Loops of Human β2 and β4 Nicotinic Acetylcholine Receptor Subunits Contribute to α3β4 Subtype Selectivity of α-Conotoxins. J. Biol. Chem. 291:23779-23792
Franco,A., Kompella,S.N., Akondi,K.B., Melaun,C., Daly,N.L., Luetje,C.W., Alewood,P.F., Craik,D.J., Adams,D.J. and Marí,F. (2012) RegIIA: an α4/7-conotoxin from the venom of Conus regius that potently blocks α3β4 nAChRs. Biochem. Pharmacol. 83:419-426
Yu, J., Zhu, X., Zhang, L., Kudryavtsev, D., Kasheverov, I., Lei, Y., Zhangsun, D., Tsetlin, V. and Luo, S. (2018) Species specificity of rat and human α7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists Neuropharmacology 139:226-237
Kompella,S.N., Hung,A., Clark,R.J., Marí,F. and Adams,D.J. (2015) Alanine scan of α-conotoxin RegIIA reveals a selective α3β4 nicotinic acetylcholine receptor antagonist J. Biol. Chem. 290:1039-1048
Kompella,S.N., Cuny,H., Hung,A. and Adams,D.J. (2015) Molecular Basis for Differential Sensitivity of α-Conotoxin RegIIA at Rat and Human Neuronal Nicotinic Acetylcholine Receptors Mol. Pharmacol. 88:993-1001
Xu,Q., Tae,H.S., Wang,Z., Jiang,T., Adams,D.J. and Yu,R. (2020) Rational Design of α-Conotoxin RegIIA Analogues Specifically Inhibiting the Human α3β2 Nicotinic Acetylcholine Receptor through Computational Scanning ACS Chem Neurosci

Internal links
Protein Precursor RegIIA precursor (5529)
Nucleic acids
Structure RegIIA NMR solution structure

External links
UniProtKB/Swiss-Prot P85013
Ncbi P85013

Tools