GeXIVA[globular] (P08687) Protein Card

General Information
Name GeXIVA[globular] (named by ConoServer)
Alternative name(s) GeXIVA[1-3]
Organism Conus generalis
Organism region Indo-Pacific
Organism diet vermivorous
Protein Type Wild type
Protein precursor GeXIVA precursor (5224)
Notes

GeXIVA inhibits Sf9 cell growth (Gao et al., 2013). There is a discrepancy in the sequence initally published in GenBank in 2012 and the sequence published in peer-reviewed journals (involving the same authors).

Yousuf et al. (2021) discovered that GeXIVA[globular] i) affects the membrane excitability of mouse DRG neurons, and ii) acts through the GABAB pathway to inhibit calcium current and iii) also reversibly potentiates GIRK1/2 channels. 1 µM GeXIVA[globular] inhibited Ba2+ current amplitude by 29+/-6%.

Classification
Conopeptide class conotoxin
Gene superfamily O1 superfamily
Cysteine framework XIV
Pharmacological family alpha conotoxin

Sequence
TCRSSGRYCRSPYDRRRRYCRRITDACV
Sequence evidence protein level
Average Mass 3452.92
Monoisotopic Mass 3450.62
Isoelectric Point 12.80
Extinction Coefficient [280nm] 4470.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α9α10H. sapiens198.6 nM+/-18.96 uM AChWu X et al. (2017)
R. norvegicus22.7 nM[11.8-43.5]0.7810 uM AChLuo,S. et al. (2015)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationAgonistRef
α9α10H. sapiens37+/-2100 nM6 uM AChWu X et al. (2017)

References
Gao,B., Zhangsun,D., Wu,Y., Lin,B., Zhu,X. and Luo,S. (2013) Expression, renaturation and biological activity of recombinant conotoxin GeXIVAWT. Appl. Microbiol. Biotechnol. 97:1223-1230
Luo,S., Zhangsun,D., Harvey,P.J., Kaas,Q., Wu,Y., Zhu,X., Hu,Y., Li,X., Tsetlin,V.I., Christensen,S., Romero,H.K., McIntyre,M., Dowell,C., Baxter,J.C., Elmslie,K.S., Craik,D.J. and McIntosh,J.M. (2015) Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist. Proc. Natl. Acad. Sci. U.S.A. 112-35
Xu, P., Kaas, Q., Wu, Y., Zhu, X., Li, X., Harvey, P.J., Zhangsun, D., Craik, D.J. and Luo, S (2020) Structure and Activity Studies of Disulfide-Deficient Analogues of αO-Conotoxin GeXIVA Journal of Medicinal Chemistry
Yousuf,A., Wu,X., Bony,A.R., Sadeghi,M., Huang,Y.H., Craik,D.J., Adams,D.J. (2021) αO-Conotoxin GeXIVA isomers modulate N-type calcium (CaV 2.2) channels and inwardly-rectifying potassium (GIRK) channels via GABAB receptor activation J Neurochem

Internal links
Protein Precursor GeXIVA precursor (5224)
Nucleic acids
Structure

External links

Tools