EpI (P00405) Protein Card

General Information
Name EpI
Alternative name(s) EpI-NH2
Organism Conus episcopatus
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Protein precursor EpI precursor (2925)
Notes Did not inhibit α3β4, α3β2, α3α5β2 or α3α5β4 nAChRs (Nicke, 2003).

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

Sequence
GCCSDPRCNMNNPD(sTy)C(nh2)
Modified residues
positionsymbolname
15sTySulfotyrosine
17nh2C-term amidation
Sequence evidence protein level
Average Mass 1866.00
Monoisotopic Mass 1864.53
Isoelectric Point 4.50
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α3β4H. sapiens64.57 nM[57.54-72.44]30 uM nicotineHo,T.N.T. et al. (2021)
α7R. norvegicus30 nM1.1 100 uM nicotineNicke,A. et al. (2003)
α7-5HT3 chimaeraG. gallus(Expressed in TRex-293 cells. )103 nM 1.43 uM nicotineNicke,A. et al. (2003)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
AChBPA. californica4.17 nM[3.09-5.89]1 nM [3H]-epibatidineHo,T.N.T. et al. (2021)
L. stagnalis>100 uM1 nM [3H]-epibatidineHo,T.N.T. et al. (2021)

Synthetic variants
EpI [sTy15Y]GCCSDPRCNMNNPDYC(nh2)
EpI [sTy15Y]-OHGCCSDPRCNMNNPDYC

References
Hu,S.H., Loughnan,M., Miller,R., Weeks,C.M., Blessing,R.H., Alewood,P.F., Lewis,R.J. and Martin,J.L. (1998) The 1.1 A resolution crystal structure of [Tyr15]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods Biochemistry 37:11425-11433
Loughnan,M., Bond,T., Atkins,A., Cuevas,J., Adams,D.J., Broxton,N.M., Livett,B.G., Down,J.G., Jones,A., Alewood,P.F. and Lewis,R.J. (1998) alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that selectively targets neuronal nicotinic acetylcholine receptors J. Biol. Chem. 273:15667-15674
Nicke,A., Samochocki,M., Loughnan,M.L., Bansal,P.S., Maelicke,A. and Lewis,R.J. (2003) Alpha-conotoxins EpI and AuIB switch subtype selectivity and activity in native versus recombinant nicotinic acetylcholine receptors. FEBS Lett. 554:219-223
Ho,T.N.T., Lee,H.S., Swaminathan,S., Goodwin,L., Rai,N., Ushay,B., Lewis,R.J. and Conibear,A.C. (2021) Posttranslational modifications of α-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding. RSC Med Chem 12:1574-1584

Internal links
Protein Precursor EpI precursor (2925)
Nucleic acids
Structure NMR structure of native EpI

External links
UniProtKB/Swiss-Prot P56638
Ncbi P56638

Tools