GeXIVA[bead] (P08686) Protein Card

General Information
Name GeXIVA[bead] (named by ConoServer)
Alternative name(s) GeXIVA[1-2]
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).

Luo et al. (2015) discovered that the three possible disulfide isomers of GeXIVA (gene predicted) have similar activity at the a9a10 nAChR.

Wang et al. (2019) reported that GeXIVA[bead] can reverse oxaliplatin-induced mechanical and cold allodynia after single and repeated intramuscular injections in rats.

Sun et al. (2019) reported that GeXIVA[bead] inhibited the growth of MDA-MB-157 cancer cell line, but not of the same cell line when the α9-nAChR subunit was knocked out.

Yousuf et al. (2021) discovered that GeXIVA[bead] does not inhibit Cav2.2 and does not affect the membrane excitability of mouse DRG neurons.


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
α1β1δεM. musculus394 nM[311-498]1.71Ach (10 uM)Luo,S. et al. (2015)
520 nM[399-670]Ach (10 uM)Xu et al. (2020)
α2β2R. norvegicus491 nM[352-684]1.23Ach (10 uM)Luo,S. et al. (2015)
1610 nM[967-2680]Ach (100 uM)Xu et al. (2020)
α2β4R. norvegicus5340 nM[4200-6790]1.02Ach (10 uM)Luo,S. et al. (2015)
α3β2R. norvegicus940 nM[602-1475]Ach (100 uM)Xu et al. (2020)
480 nM[275-837]0.73Ach (10 uM)Luo,S. et al. (2015)
α3β4R. norvegicus5400 nM[3480-8410]1.13Ach (10 uM)Luo,S. et al. (2015)
6930 nM[3559-13470]Ach (100 uM)Xu et al. (2020)
α4β2R. norvegicus1280 nM[953-1720]0.88Ach (10 uM)Luo,S. et al. (2015)
α4β4R. norvegicus2510 nM[1630-3870]0.79Ach (10 uM)Luo,S. et al. (2015)
α6β3β4R. norvegicus1380 nM[854-2239]Ach (100 uM)Xu et al. (2020)
α6/α3β2β3R. norvegicus450 nM[353-574]1.12Ach (10 uM)Luo,S. et al. (2015)
α6/α3β4R. norvegicus806 nM[664-980]1.36Ach (10 uM)Luo,S. et al. (2015)
α7R. norvegicus660 nM[429-1011]Ach (200 uM)Xu et al. (2020)
415 nM[264-655]1.12Ach (10 uM)Luo,S. et al. (2015)
α9α10R. norvegicus4.61 nM[3.18-6.65]0.56Ach (10 uM)Luo,S. et al. (2015)
12 nM[9-14]Ach (10 uM)Xu et al. (2020)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationAgonistRef
α9α10H. sapiens68+/-2100 nMAch (6 uM)Wu X et al. (2017)

Synthetic variants
GeXIVA[C20A,C27A]TCRSSGRYCRSPYDRRRRYARRITDAAV
GeXIVA[C20S,C27S]TCRSSGRYCRSPYDRRRRYSRRITDASV
GeXIVA[C2A,C9A,C20A,C27A]TARSSGRYARSPYDRRRRYARRITDAAV
GeXIVA[C2A,C9A,C20S,C27S]TARSSGRYARSPYDRRRRYSRRITDASV
GeXIVA[C2A,C9A]TARSSGRYARSPYDRRRRYCRRITDACV
GeXIVA[C2S,C9S,C20A,C27A]TSRSSGRYSRSPYDRRRRYARRITDAAV
GeXIVA[C2S,C9S,C20S,C27S]TSRSSGRYSRSPYDRRRRYSRRITDASV
GeXIVA[C2S,C9S]TSRSSGRYSRSPYDRRRRYCRRITDACV

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
Sun,Z., Bao,J., Zhangsun,M., Dong,S., Zhangsun,D. and Luo,S. (2020) αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors Mar Drugs 18:195
Yousuf A, Wu X, Bony AR, Sadeghi M, Huang YH, Craik DJ, Adams DJ (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

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