CA1A_CONVC
ID CA1A_CONVC Reviewed; 66 AA.
AC P69747;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 71.
DE RecName: Full=Alpha-conotoxin Vc1a {ECO:0000303|PubMed:15170751};
DE Short=Alpha-Vc1a;
DE AltName: Full=ACV1 {ECO:0000303|PubMed:15770155};
DE AltName: Full=Vc1.1 {ECO:0000303|PubMed:12779345};
DE Flags: Precursor;
OS Conus victoriae (Queen Victoria cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX NCBI_TaxID=319920;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION OF VC1.1, AND SYNTHESIS OF 50-65
RP (VC1.1).
RC TISSUE=Venom duct;
RX PubMed=12779345; DOI=10.1021/bi034043e;
RA Sandall D.W., Satkunanathan N., Keays D.A., Polidano M.A., Liping X.,
RA Pham V., Down J.G., Khalil Z., Livett B.G., Gayler K.R.;
RT "A novel alpha-conotoxin identified by gene sequencing is active in
RT suppressing the vascular response to selective stimulation of sensory
RT nerves in vivo.";
RL Biochemistry 42:6904-6911(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, AMIDATION AT CYS-65,
RP HYDROXYLATION AT PRO-55, GAMMA-CARBOXYGLUTAMATION AT GLU-63, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom duct;
RX PubMed=15170751; DOI=10.1002/jms.624;
RA Jakubowski J.A., Keays D.A., Kelley W.P., Sandall D.W., Bingham J.-P.,
RA Livett B.G., Gayler K.R., Sweedler J.V.;
RT "Determining sequences and post-translational modifications of novel
RT conotoxins in Conus victoriae using cDNA sequencing and mass
RT spectrometry.";
RL J. Mass Spectrom. 39:548-557(2004).
RN [3]
RP FUNCTION OF VC1.1, AND SYNTHESIS OF 50-65 (VC1.1).
RX PubMed=15770155; DOI=10.1097/00001756-200504040-00012;
RA Lang P.M., Burgstahler R., Haberberger R.V., Sippel W., Grafe P.;
RT "A conus peptide blocks nicotinic receptors of unmyelinated axons in human
RT nerves.";
RL NeuroReport 16:479-483(2005).
RN [4]
RP FUNCTION OF VC1.1, AND SYNTHESIS OF 50-65 (VC1.1).
RX PubMed=17101979; DOI=10.1073/pnas.0608715103;
RA Vincler M., Wittenauer S., Parker R., Ellison M., Olivera B.M.,
RA McIntosh J.M.;
RT "Molecular mechanism for analgesia involving specific antagonism of
RT alpha9alpha10 nicotinic acetylcholine receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17880-17884(2006).
RN [5]
RP FUNCTION OF VC1A AND VC1.1, AND SYNTHESIS OF 50-65 (VC1A AND VC1.1).
RX PubMed=17804600; DOI=10.1124/mol.107.040568;
RA Nevin S.T., Clark R.J., Klimis H., Christie M.J., Craik D.J., Adams D.J.;
RT "Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for
RT alpha-conotoxins?";
RL Mol. Pharmacol. 72:1406-1410(2007).
RN [6]
RP FUNCTION OF VC1A AND VC1.1 ON GABA(B) RECEPTOR, AND SYNTHESIS OF 50-65
RP (VC1A AND VC1.1).
RX PubMed=18945902; DOI=10.1523/jneurosci.3594-08.2008;
RA Callaghan B., Haythornthwaite A., Berecki G., Clark R.J., Craik D.J.,
RA Adams D.J.;
RT "Analgesic alpha-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels
RT in rat sensory neurons via GABAB receptor activation.";
RL J. Neurosci. 28:10943-10951(2008).
RN [7]
RP FUNCTION OF VC1.1, SYNTHESIS OF 50-65 (VC1.1), AND MUTAGENESIS OF GLY-50;
RP SER-53; ASP-54; PRO-55; ARG-56; ASN-58; TYR-59; ASP-60; HIS-61; PRO-62;
RP GLU-63 AND ILE-64.
RX PubMed=19447885; DOI=10.1074/jbc.m109.015339;
RA Halai R., Clark R.J., Nevin S.T., Jensen J.E., Adams D.J., Craik D.J.;
RT "Scanning mutagenesis of alpha-conotoxin Vc1.1 reveals residues crucial for
RT activity at the alpha9alpha10 nicotinic acetylcholine receptor.";
RL J. Biol. Chem. 284:20275-20284(2009).
RN [8]
RP FUNCTION OF VC1.1, SYNTHESIS OF 50-65 (VC1.1), AND MUTAGENESIS OF ASN-58.
RX PubMed=23566299; DOI=10.1021/jm400041h;
RA Yu R., Kompella S.N., Adams D.J., Craik D.J., Kaas Q.;
RT "Determination of the alpha-conotoxin Vc1.1 binding site on the
RT alpha9alpha10 nicotinic acetylcholine receptor.";
RL J. Med. Chem. 56:3557-3567(2013).
RN [9]
RP FUNCTION OF VC1.1, SYNTHESIS OF 50-65 (VC1.1), AND MUTAGENESIS OF CYS-52
RP AND 58-ASN--CYS-65.
RX PubMed=26948522; DOI=10.1002/anie.201600297;
RA Carstens B.B., Berecki G., Daniel J.T., Lee H.S., Jackson K.A., Tae H.S.,
RA Sadeghi M., Castro J., O'Donnell T., Deiteren A., Brierley S.M.,
RA Craik D.J., Adams D.J., Clark R.J.;
RT "Structure-activity studies of cysteine-rich alpha-conotoxins that inhibit
RT high-voltage-activated calcium channels via GABA(B) receptor activation
RT reveal a minimal functional motif.";
RL Angew. Chem. Int. Ed. 55:4692-4696(2016).
RN [10]
RP FUNCTION OF CYCLIC VC1.1, SYNTHESIS OF 50-65 (VC1.1), AND PHARMACEUTICAL.
RX PubMed=29194563; DOI=10.1111/bph.14115;
RA Castro J., Grundy L., Deiteren A., Harrington A.M., O'Donnell T.,
RA Maddern J., Moore J., Garcia-Caraballo S., Rychkov G.Y., Yu R., Kaas Q.,
RA Craik D.J., Adams D.J., Brierley S.M.;
RT "Cyclic analogues of alpha-conotoxin Vc1.1 inhibit colonic nociceptors and
RT provide analgesia in a mouse model of chronic abdominal pain.";
RL Br. J. Pharmacol. 175:2384-2398(2018).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF CYS-65.
RX PubMed=32101438; DOI=10.1021/acs.jmedchem.9b01536;
RA Liang J., Tae H.S., Xu X., Jiang T., Adams D.J., Yu R.;
RT "Dimerization of alpha-conotoxins as a strategy to enhance the inhibition
RT of the human alpha7 and alpha9alpha10 nicotinic acetylcholine Receptors.";
RL J. Med. Chem. 63:2974-2985(2020).
RN [12]
RP STRUCTURE BY NMR OF 50-65 (VC1.1).
RX PubMed=16754662; DOI=10.1074/jbc.m604550200;
RA Clark R.J., Fischer H., Nevin S.T., Adams D.J., Craik D.J.;
RT "The synthesis, structural characterisation and receptor specificity of the
RT alpha-conotoxin Vc1.1.";
RL J. Biol. Chem. 281:23254-23263(2006).
RN [13]
RP STRUCTURE BY NMR OF 50-66 (CYCLIC VC1.1), AND MUTAGENESIS OF GLY-66.
RX PubMed=20533477; DOI=10.1002/anie.201000620;
RA Clark R.J., Jensen J., Nevin S.T., Callaghan B.P., Adams D.J., Craik D.J.;
RT "The engineering of an orally active conotoxin for the treatment of
RT neuropathic pain.";
RL Angew. Chem. Int. Ed. 49:6545-6548(2010).
RN [14]
RP STRUCTURE BY NMR OF 50-65 (VC1.1 AND DICARBA ANALOGS), AND FUNCTION OF
RP VC1.1 AND DICARBA ANALOGS.
RX PubMed=23768016; DOI=10.1021/cb4002393;
RA van Lierop B.J., Robinson S.D., Kompella S.N., Belgi A., McArthur J.R.,
RA Hung A., MacRaild C.A., Adams D.J., Norton R.S., Robinson A.J.;
RT "Dicarba alpha-conotoxin Vc1.1 analogues with differential selectivity for
RT nicotinic acetylcholine and GABAB receptors.";
RL ACS Chem. Biol. 8:1815-1821(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF L- AND D-CYCLIC VC1.1.
RX PubMed=25168664; DOI=10.1002/anie.201406563;
RA Wang C.K., King G.J., Northfield S.E., Ojeda P.G., Craik D.J.;
RT "Racemic and quasi-racemic X-ray structures of cyclic disulfide-rich
RT peptide drug scaffolds.";
RL Angew. Chem. Int. Ed. 53:11236-11241(2014).
RN [16]
RP STRUCTURE BY NMR OF 50-66 (CYCLIC VC1.1).
RX PubMed=26290113; DOI=10.1038/srep13264;
RA Yu R., Seymour V.A., Berecki G., Jia X., Akcan M., Adams D.J., Kaas Q.,
RA Craik D.J.;
RT "Less is more: design of a highly stable disulfide-deleted mutant of
RT analgesic cyclic alpha-conotoxin Vc1.1.";
RL Sci. Rep. 5:13264-13264(2015).
RN [17]
RP STRUCTURE BY NMR OF CYCLIC [D11A; E14A]VC1.1, AND MUTAGENESIS OF ASP-60 AND
RP GLU-63.
RX PubMed=29746088; DOI=10.1021/acschembio.8b00190;
RA Sadeghi M., Carstens B.B., Callaghan B.P., Daniel J.T., Tae H.S.,
RA O'Donnell T., Castro J., Brierley S.M., Adams D.J., Craik D.J., Clark R.J.;
RT "Structure-activity studies reveal the molecular basis for GABAB-receptor
RT mediated inhibition of high voltage-activated calcium channels by alpha-
RT conotoxin Vc1.1.";
RL ACS Chem. Biol. 13:1577-1587(2018).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin (native toxin Vc1a; hydroxylated and gamma-carboxylated)
CC blocks alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (IC(50)=62.9 nM)
CC (PubMed:17804600). In contrast to the non-post-translationally modified
CC analog Vc1.1, Vc1a does not inhibit high voltage-activated (HVA)
CC calcium channel currents (PubMed:18945902). In vivo, in contrast to
CC Vc1.1, Vc1a does not show analgesic effects in rat models of
CC neuropathic pain (PubMed:17804600). {ECO:0000269|PubMed:17804600,
CC ECO:0000269|PubMed:18945902}.
CC -!- FUNCTION: The synthetic peptide Vc1.1 (a non-hydroxylated and non-
CC gamma-carboxylated analog of Vc1a) has two types of targets. It blocks
CC alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (on rat receptors, IC(50)=19-109
CC nM) (with preference for rat over human receptors) and inhibits high
CC voltage-activated (HVA) calcium channel (Cav2.2, Cav2.3) currents by
CC acting on GABA(B) receptors (GABBR1 and GABBR2) (IC(50)=1.7 nM)
CC (PubMed:17101979, PubMed:17804600, PubMed:18945902, PubMed:19447885,
CC PubMed:23566299, PubMed:26948522, PubMed:20533477, PubMed:23768016). It
CC also shows moderate inhibition on alpha-6/alpha-3-beta-2-beta-3
CC (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC(50)=140 nM) and alpha-6/alpha-3-beta-
CC 4 (CHRNA6/CHRNA3-CHRNB4) (IC(50)=980 nM) (PubMed:17101979). On alpha-9-
CC alpha-10/CHRNA9-CHRNA10 nAChR, it most likely interacts with the alpha-
CC 10(+)/alpha-9(-)interface of the receptor (PubMed:23566299). In vivo,
CC it acts as a powerful analgesic in rat models of neuropathic pain
CC (PubMed:17804600). {ECO:0000269|PubMed:12779345,
CC ECO:0000269|PubMed:15770155, ECO:0000269|PubMed:17101979,
CC ECO:0000269|PubMed:17804600, ECO:0000269|PubMed:18945902,
CC ECO:0000269|PubMed:19447885, ECO:0000269|PubMed:20533477,
CC ECO:0000269|PubMed:23566299, ECO:0000269|PubMed:23768016,
CC ECO:0000269|PubMed:26948522}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15170751}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:15170751}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- PTM: Vc1.1 is described as having no post-translational modifications
CC (except C-terminal amidation), whereas Vc1a contains a hydroxyproline
CC at Pro-55 and a 4-carboxyglutamate at Glu-63 (and a C-terminal
CC amidation) (PubMed:17101979, PubMed:17804600).
CC {ECO:0000305|PubMed:17101979, ECO:0000305|PubMed:17804600}.
CC -!- PTM: Hydroxylation of Pro-55 is not important for inhibition of alpha-
CC 9-alpha-10/CHRNA9-CHRNA10 nAChRs, since [P6O]Vc1.1 (Pro-55
CC hydroxylated) shows similar inhibition than native toxin (IC(50)=99.1
CC nM) (PubMed:17804600). In contrast, hydroxylation of Pro-55 seems to
CC impair inhibition of HVA calcium channel currents, since [P6O]Vc1.1 has
CC no effect on HVA calcium channel currents (PubMed:18945902). In vivo,
CC hydroxylation of Pro-55 seems to induce the loss of analgesic effects
CC in rat models of neuropathic pain, since [P6O]Vc1.1 has no effect on
CC mechanical allodynia (PubMed:17804600). {ECO:0000269|PubMed:17804600,
CC ECO:0000269|PubMed:18945902}.
CC -!- PTM: Gamma-carboxylation of Glu-63 is not important for inhibition of
CC alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs, since [E14gamma]Vc1.1
CC (carboxyglutamate at Glu-63) shows similar inhibition than native toxin
CC (IC(50)=65.3 nM) (PubMed:17804600). In contrast, gamma-carboxylation of
CC Glu-63 seems to impair inhibition of HVA calcium channel currents,
CC since [E14gamma]Vc1.1 has no effect on HVA calcium channel currents
CC (PubMed:18945902). {ECO:0000269|PubMed:17804600,
CC ECO:0000269|PubMed:18945902}.
CC -!- PTM: Non-native isomers 'ribbon' (with disulfide connectivity C1-C4;
CC C2-C3) and 'beads' (with disulfide connectivity C1-C2; C3-C4) of Vc1.1
CC also inhibit HVA calcium channel currents in rat DRG neurons (20-30%
CC inhibition at 1 uM toxin) (PubMed:26948522). It has been shown that
CC both reduced and alkylated Vc1.1 have no effect on HVA calcium channel
CC currents. The observed activity can be attributed to specific isomers
CC (PubMed:26948522). {ECO:0000269|PubMed:26948522}.
CC -!- PTM: [C3S]Vc1.1(1-8) mutant is C-terminally amidated.
CC {ECO:0000269|PubMed:26948522}.
CC -!- MASS SPECTROMETRY: Mass=1866.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15170751};
CC -!- MASS SPECTROMETRY: Mass=1866; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:16754662};
CC -!- PHARMACEUTICAL: Cyclic versions of Vc1.1 evoke significant anti-
CC nociceptive actions in animal model of chronic visceral
CC hypersensitivity (CVH), suggesting that they could be novel candidates
CC for treatment of chronic visceral pain (CVP).
CC {ECO:0000305|PubMed:29194563}.
CC -!- MISCELLANEOUS: The synthetic peptide Vc1.1 (a non-hydroxylated and non-
CC gamma-carboxylated analog of Vc1a) shows weak inhibition on nAChRs
CC composed of alpha-3-alpha-5-beta-2/CHRNA3-CHRNA5-CHRNB2 (IC(50)=7.2
CC uM), alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=5.5-7.3 uM), alpha-3-beta-
CC 4/CHRNA3-CHRNB4 (IC(50)=4.2 uM), alpha-3-alpha-5-beta-4/CHRNA3-CHRNA5-
CC CHRNB4 (IC(50)>30 uM), alpha-4-beta-2/CHRNA4-CHRNB2 (IC(50)>30 uM),
CC alpha-4-beta-4/CHRNA4-CHRNB4 (IC(50)>30 uM), rat alpha-7/CHRNA7
CC (IC(50)=7.1 uM) and alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-
CC CHRND (IC(50)>30 uM) subunits. {ECO:0000269|PubMed:16754662,
CC ECO:0000269|PubMed:19447885, ECO:0000269|PubMed:32101438}.
CC -!- MISCELLANEOUS: cVc1.1 is a cyclic peptide with inhibitory activity on
CC alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (IC(50)=766 nM) and a high
CC potency at inhibiting HVA calcium channels in mice DRG neurons
CC (IC(50)=0.3 nM) (PubMed:20533477). Toxin cVc1.1[D11A; E14A] is a cyclic
CC peptide with a very low inhibitory activity on alpha-9-alpha-10/CHRNA9-
CC CHRNA10 nAChRs (IC(50)>17 uM) and a high potency at inhibiting HVA
CC calcium channels in mice DRG neurons (IC(50)=3.3 nM) (PubMed:29746088).
CC Both of them show antinociceptive actions, with greater efficacy in a
CC model of animal chronic visceral hypersensitivity (CVH)
CC (PubMed:29194563, PubMed:29746088). {ECO:0000269|PubMed:20533477,
CC ECO:0000269|PubMed:29194563, ECO:0000269|PubMed:29746088}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR PDB; 2H8S; NMR; -; A=50-65.
DR PDB; 2MFX; NMR; -; A=50-65.
DR PDB; 2MFY; NMR; -; A=50-65.
DR PDB; 2MG6; NMR; -; A=50-65.
DR PDB; 2N07; NMR; -; X=50-65.
DR PDB; 4TTL; X-ray; 1.70 A; A=50-65.
DR PDB; 6CGX; NMR; -; A=50-65.
DR PDB; 7KNN; NMR; -; A=50-65.
DR PDBsum; 2H8S; -.
DR PDBsum; 2MFX; -.
DR PDBsum; 2MFY; -.
DR PDBsum; 2MG6; -.
DR PDBsum; 2N07; -.
DR PDBsum; 4TTL; -.
DR PDBsum; 6CGX; -.
DR PDBsum; 7KNN; -.
DR AlphaFoldDB; P69747; -.
DR BMRB; P69747; -.
DR SMR; P69747; -.
DR ConoServer; 499; VcIA precursor.
DR EvolutionaryTrace; P69747; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR InterPro; IPR018072; Conotoxin_a-typ_CS.
DR Pfam; PF07365; Toxin_8; 1.
DR PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Gamma-carboxyglutamic acid; Hydroxylation; Ion channel impairing toxin;
KW Neurotoxin; Pharmaceutical; Postsynaptic neurotoxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..47
FT /evidence="ECO:0000305"
FT /id="PRO_0000034896"
FT PEPTIDE 50..65
FT /note="Alpha-conotoxin Vc1a"
FT /evidence="ECO:0000305|PubMed:12779345"
FT /id="PRO_0000034897"
FT REGION 53..55
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT REGION 54..56
FT /note="Key region for inhibition of alpha-9-alpha-
FT 10/CHRNA9-CHRNA10 nAChR"
FT /evidence="ECO:0000305|PubMed:19447885"
FT REGION 60..64
FT /note="Key region for inhibition of alpha-9-alpha-
FT 10/CHRNA9-CHRNA10 nAChR"
FT /evidence="ECO:0000305|PubMed:19447885"
FT MOD_RES 55
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:15170751"
FT MOD_RES 63
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000269|PubMed:15170751"
FT MOD_RES 65
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:15170751"
FT DISULFID 51..57
FT /evidence="ECO:0000269|PubMed:16754662,
FT ECO:0000269|PubMed:25168664, ECO:0000269|PubMed:29746088,
FT ECO:0000312|PDB:2H8S, ECO:0000312|PDB:4TTL,
FT ECO:0000312|PDB:6CGX"
FT DISULFID 52..65
FT /evidence="ECO:0000269|PubMed:16754662,
FT ECO:0000269|PubMed:25168664, ECO:0000269|PubMed:29746088,
FT ECO:0000312|PDB:2H8S, ECO:0000312|PDB:4TTL,
FT ECO:0000312|PDB:6CGX"
FT MUTAGEN 50
FT /note="G->A,D: Vc1.1; No change in potency of inhibition of
FT rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No change in
FT potency of inhibition of HVA calcium channels in rat/mouse
FT DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 50
FT /note="G->K: Vc1.1; No change in potency of inhibition of
FT rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. Decrease in
FT potency of inhibition of HVA calcium channels in rat/mouse
FT DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 52
FT /note="C->S: In [C3S]Vc1.1(1-8); Shows similar potency of
FT inhibition of HVA calcium currents. Shows 95% inhibition of
FT human alpha-7/CHRNA7, but no inhibition of human alpha-9-
FT alpha-10/CHRNA9-CHRNA10 AChR."
FT /evidence="ECO:0000269|PubMed:26948522"
FT MUTAGEN 53
FT /note="S->A: Vc1.1; 2.5-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 53
FT /note="S->D: Vc1.1; 1.7-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 53
FT /note="S->K: Vc1.1; 1.7-fold increase in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons. 2-fold increase in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR;
FT when associated with A-58."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 54
FT /note="D->A,K: Vc1.1; Almost complete loss of potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 55
FT /note="P->A,D,K: Vc1.1; Almost complete loss of potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 56
FT /note="R->A,D,K: Vc1.1; Almost complete loss of potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 58..65
FT /note="Missing: In [C3S]Vc1.1(1-8); Shows similar potency
FT of inhibition of HVA calcium currents. Shows 95% inhibition
FT of human alpha-7/CHRNA7, but no inhibition of human alpha-
FT 9-alpha-10/CHRNA9-CHRNA10 AChR."
FT /evidence="ECO:0000269|PubMed:26948522"
FT MUTAGEN 58
FT /note="N->A: Vc1.1; 2.2-fold increase in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT 30-fold increase in potency of inhibition of rat alpha-3-
FT beta-2/CHRNA3-CHRNB2 nAChR. Decrease in potency of
FT inhibition of HVA calcium channels in rat/mouse DRG
FT neurons. 2-fold increase in potency of inhibition of rat
FT alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR; when associated with
FT K-53."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 58
FT /note="N->D: Vc1.1; No change in potency of inhibition of
FT rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No change in
FT potency of inhibition of HVA calcium channels in rat/mouse
FT DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 58
FT /note="N->G: Vc1.1; 1.9-fold increase in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR."
FT /evidence="ECO:0000269|PubMed:19447885"
FT MUTAGEN 58
FT /note="N->I: Vc1.1; 1.7-fold increase in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT 25-fold increase in potency of inhibition of rat alpha-3-
FT beta-2/CHRNA3-CHRNB2 nAChR. 7-fold increase in potency of
FT inhibition of rat alpha-7/CHRNA7 nAChR."
FT /evidence="ECO:0000269|PubMed:19447885"
FT MUTAGEN 58
FT /note="N->K: Vc1.1; Complete loss of potency of inhibition
FT of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No change in
FT potency of inhibition of HVA calcium channels in rat/mouse
FT DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 58
FT /note="N->L: Vc1.1; 1.7-fold increase in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. 2-
FT fold increase in potency of inhibition of rat alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:19447885"
FT MUTAGEN 59
FT /note="Y->A,K: Vc1.1; No change in potency of inhibition of
FT rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. Decrease in
FT potency of inhibition of HVA calcium channels in rat/mouse
FT DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 59
FT /note="Y->D: Vc1.1; 5-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 60
FT /note="D->A: Vc1.1; 5-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons. Toxin cVc1.1[D11A; E14A]; important
FT decrease in potency of inhibition of alpha-9-alpha-
FT 10/CHRNA9-CHRNA10 nAChR. Very potent in inhibition of HVA
FT calcium channels in mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 60
FT /note="D->K: Vc1.1; 5-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 61
FT /note="H->A: Vc1.1; 10-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 61
FT /note="H->D,K: Vc1.1; About 4.1-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 62
FT /note="P->A: Vc1.1; 3.3-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 62
FT /note="P->D,K: Vc1.1; Complete loss of potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 63
FT /note="E->A: Vc1.1; About 3.3-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons. Toxin cVc1.1[D11A; E14A]; important
FT decrease in potency of inhibition of alpha-9-alpha-
FT 10/CHRNA9-CHRNA10 nAChR. Very potent in inhibition of HVA
FT calcium channels in mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 63
FT /note="E->D: Vc1.1; About 2-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 63
FT /note="E->K: Vc1.1; About 3-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 64
FT /note="I->A: Vc1.1; 5-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No
FT change in potency of inhibition of HVA calcium channels in
FT rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 64
FT /note="I->D: Vc1.1; Complete loss of potency of inhibition
FT of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR. No change in
FT potency of inhibition of HVA calcium channels in rat/mouse
FT DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 64
FT /note="I->K: Vc1.1; 2.5-fold decrease in potency of
FT inhibition of rat alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR.
FT Decrease in potency of inhibition of HVA calcium channels
FT in rat/mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:19447885,
FT ECO:0000269|PubMed:29746088"
FT MUTAGEN 65
FT /note="C->CGRRRRGGCCSDPRCNYDHPEIC: Vc1.1 dimer; No
FT important change in activity on alpha-9-alpha-10/CHRNA9-
FT CHRNA10 nAChRs and on alpha-7/CHRNA7 nAChRs."
FT /evidence="ECO:0000269|PubMed:32101438"
FT MUTAGEN 66
FT /note="G->GGAAGG: Toxin cVc1.1[D11A; E14A]; important
FT decrease in potency of inhibition of alpha-9-alpha-
FT 10/CHRNA9-CHRNA10 nAChR. Very potent in inhibition of HVA
FT calcium channels in mouse DRG neurons."
FT /evidence="ECO:0000269|PubMed:29746088"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:4TTL"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:4TTL"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:4TTL"
SQ SEQUENCE 66 AA; 7258 MW; C55B0951D5E7A28D CRC64;
MGMRMMFTVF LLVVLATTVV SSTSGRREFR GRNAAAKASD LVSLTDKKRG CCSDPRCNYD
HPEICG
