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

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

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

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.


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. musculus520 nM[399-670]Ach (10 uM)Xu et al. (2020)
394 nM[311-498]1.71Ach (10 uM)Luo,S. et al. (2015)
α2β2R. norvegicus1610 nM[967-2680]Ach (100 uM)Xu et al. (2020)
491 nM[352-684]1.23Ach (10 uM)Luo,S. et al. (2015)
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. norvegicus6930 nM[3559-13470]Ach (100 uM)Xu et al. (2020)
5400 nM[3480-8410]1.13Ach (10 uM)Luo,S. et al. (2015)
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. norvegicus415 nM[264-655]1.12Ach (10 uM)Luo,S. et al. (2015)
660 nM[429-1011]Ach (200 uM)Xu et al. (2020)
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)

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
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

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

External links

Tools