O16E_CONCT
ID O16E_CONCT Reviewed; 66 AA.
AC Q9N633;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 71.
DE RecName: Full=Omega conotoxin-CVIE {ECO:0000303|PubMed:19892914};
DE AltName: Full=Omega conotoxin-CVIE-2 {ECO:0000305};
DE Flags: Precursor; Fragment;
OS Conus catus (Cat cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=101291;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15306367; DOI=10.1098/rspb.2004.2708;
RA Duda T.F. Jr., Palumbi S.R.;
RT "Gene expression and feeding ecology: evolution of piscivory in the
RT venomous gastropod genus Conus.";
RL Proc. R. Soc. B 271:1165-1174(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 41-65, FUNCTION, BIOASSAY, AND
RP 3D-STRUCTURE MODELING.
RC TISSUE=Venom duct;
RX PubMed=19892914; DOI=10.1124/mol.109.058834;
RA Berecki G., Motin L., Haythornthwaite A., Vink S., Bansal P.,
RA Drinkwater R., Wang C.I., Moretta M., Lewis R.J., Alewood P.F.,
RA Christie M.J., Adams D.J.;
RT "Analgesic (omega)-conotoxins CVIE and CVIF selectively and voltage-
RT dependently block recombinant and native N-type calcium channels.";
RL Mol. Pharmacol. 77:139-148(2010).
RN [3]
RP ERRATUM OF PUBMED:19892914.
RX DOI=10.1124/mol.80.2.356;
RA Berecki G., Motin L., Haythornthwaite A., Vink S., Bansal P.,
RA Drinkwater R., Wang C.I., Moretta M., Lewis R.J., Alewood P.F.,
RA Christie M.J., Adams D.J.;
RT "Correction to 'Analgesic omega-Conotoxins CVIE and CVIF Selectively and
RT Voltage-Dependently Block Recombinant and Native N-Type Calcium
RT Channels'.";
RL Mol. Pharmacol. 80:356-356(2011).
RN [4]
RP MUTAGENESIS OF ARG-50.
RX PubMed=24628243; DOI=10.1111/bph.12686;
RA Berecki G., Daly N.L., Huang Y.H., Vink S., Craik D.J., Alewood P.F.,
RA Adams D.J.;
RT "Effects of arginine 10 to lysine substitution on omega-conotoxin CVIE and
RT CVIF block of Cav2.2 channels.";
RL Br. J. Pharmacol. 171:3313-3327(2014).
CC -!- FUNCTION: Omega-conotoxins act at presynaptic membranes, they bind and
CC block voltage-gated calcium channels. This toxin blocks N-type calcium
CC channels (Cav2.2/CACNA1B). It shows a higher potency when
CC Cav2.2/CACNA1B is only expressed with the ancillary subunit CACNB3
CC (IC(50)=0.12 nM) than on Cav2.2/CACNA1B expressed with the ancillary
CC subunits CACNA2D1 and CACNB3 (IC(50)=2.6 nM). The Cav2.2/CACNA1B block
CC by this toxin is voltage-independent, whereas the recovery from toxin
CC block is voltage-dependent (PubMed:19892914). There is a low recovery
CC at physiological membrane potential and a high recovery with
CC hyperpolarized potential (PubMed:19892914). This indicates that the
CC toxin has a higher affinity for Cav2.2/CACNA1B in the inactivated state
CC (PubMed:19892914). It is noteworthy that ancillary subunits beta
CC modulate recovery from this toxin block (PubMed:19892914).
CC Cav2.2/CACNA1B expressed with the ancillary subunit CACNB2a (isoform
CC 2a) almost recover completely from this toxin block, whereas
CC Cav2.2/CACNA1B expressed with CACNB3 exhibits relatively weak recovery
CC (PubMed:19892914). Inhibition by this toxin of excitatory synaptic
CC transmission is reversible (PubMed:19892914). In vivo, when tested on
CC rat model of persistent pain, this toxin blocks chronic pain behavior
CC (PubMed:19892914). {ECO:0000269|PubMed:19892914}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:19892914}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:19892914}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P05484}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC -!- MISCELLANEOUS: Does not show effect on Cav1.2/CACNA1C, Cav1.3/CACNA1D,
CC and Cav2.3/CACNA1E and shows a very little inhibition on
CC Cav2.1/CACNA1A. {ECO:0000269|PubMed:19892914}.
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
CC -!- CAUTION: This sequence is published under the name CVIE but another
CC peptide with a different sequence and a different pharmacological
CC family is already published with this name (see AC P69751).
CC {ECO:0000305}.
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DR EMBL; AF174214; AAF89878.1; -; Genomic_DNA.
DR EMBL; AF174215; AAF89879.1; -; Genomic_DNA.
DR EMBL; AF174219; AAF89883.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9N633; -.
DR SMR; Q9N633; -.
DR ConoServer; 1188; CVIE precursor.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR InterPro; IPR004214; Conotoxin.
DR InterPro; IPR012321; Conotoxin_omega-typ_CS.
DR Pfam; PF02950; Conotoxin; 1.
DR PROSITE; PS60004; OMEGA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW Amidation; Disulfide bond; Secreted; Signal.
FT SIGNAL <1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..40
FT /evidence="ECO:0000305"
FT /id="PRO_0000446315"
FT PEPTIDE 41..65
FT /note="Omega conotoxin-CVIE"
FT /evidence="ECO:0000305|PubMed:19892914"
FT /id="PRO_5007717414"
FT MOD_RES 65
FT /note="Cysteine amide"
FT /evidence="ECO:0000250|UniProtKB:P05484"
FT DISULFID 41..56
FT /evidence="ECO:0000250|UniProtKB:P05484"
FT DISULFID 48..60
FT /evidence="ECO:0000250|UniProtKB:P05484"
FT DISULFID 55..65
FT /evidence="ECO:0000250|UniProtKB:P05484"
FT MUTAGEN 50
FT /note="R->K: Alters the kinetics of action and improves
FT reversibility without diminishing conotoxin potency and
FT specificity for Cav2.2/CACNA1B and without diminishing the
FT serum stability."
FT /evidence="ECO:0000269|PubMed:19892914"
FT NON_TER 1
SQ SEQUENCE 66 AA; 7053 MW; E445338A6968A1AC CRC64;
VVIVAVLLLT ACQLITANDS RGTQKHRALR SDTKLSMSTR CKGKGASCRR TSYDCCTGSC
RSGRCG
