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

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

Target	Organism	IC50		n_hill	Agonist	Ref
α1β1δε	M. musculus	394 nM	[311-498]	1.71	Ach (10 uM)	Luo,S. et al. (2015)
		520 nM	[399-670]		Ach (10 uM)	Xu et al. (2020)
α2β2	R. norvegicus	491 nM	[352-684]	1.23	Ach (10 uM)	Luo,S. et al. (2015)
		1610 nM	[967-2680]		Ach (100 uM)	Xu et al. (2020)
α2β4	R. norvegicus	5340 nM	[4200-6790]	1.02	Ach (10 uM)	Luo,S. et al. (2015)
α3β2	R. norvegicus	940 nM	[602-1475]		Ach (100 uM)	Xu et al. (2020)
		480 nM	[275-837]	0.73	Ach (10 uM)	Luo,S. et al. (2015)
α3β4	R. norvegicus	5400 nM	[3480-8410]	1.13	Ach (10 uM)	Luo,S. et al. (2015)
		6930 nM	[3559-13470]		Ach (100 uM)	Xu et al. (2020)
α4β2	R. norvegicus	1280 nM	[953-1720]	0.88	Ach (10 uM)	Luo,S. et al. (2015)
α4β4	R. norvegicus	2510 nM	[1630-3870]	0.79	Ach (10 uM)	Luo,S. et al. (2015)
α6β3β4	R. norvegicus	1380 nM	[854-2239]		Ach (100 uM)	Xu et al. (2020)
α6/α3β2β3	R. norvegicus	450 nM	[353-574]	1.12	Ach (10 uM)	Luo,S. et al. (2015)
α6/α3β4	R. norvegicus	806 nM	[664-980]	1.36	Ach (10 uM)	Luo,S. et al. (2015)
α7	R. norvegicus	660 nM	[429-1011]		Ach (200 uM)	Xu et al. (2020)
		415 nM	[264-655]	1.12	Ach (10 uM)	Luo,S. et al. (2015)
α9α10	R. norvegicus	4.61 nM	[3.18-6.65]	0.56	Ach (10 uM)	Luo,S. et al. (2015)
		12 nM	[9-14]		Ach (10 uM)	Xu et al. (2020)

Target	Organism	% inhibition		Concentration	Agonist	Ref
α9α10	H. sapiens	68	+/-2	100 nM	Ach (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

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,A.R., Sadeghi,M., Huang,Y.H., Craik,D.J., Adams,D.J. (2021) αO-Conotoxin GeXIVA isomers modulate N-type calcium (Ca_V 2.2) channels and inwardly-rectifying potassium (GIRK) channels via GABAB receptor activation J Neurochem

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