ID   O16F_CONCT              Reviewed;          25 AA.
AC   P0DQD4;
DT   13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT   13-FEB-2019, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Omega conotoxin-CVIF {ECO:0000303|PubMed:19892914};
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 [MRNA], SYNTHESIS, FUNCTION, BIOASSAY, AND 3D-STRUCTURE
RP   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   [2]
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   [3]
RP   FUNCTION, AND MUTAGENESIS OF ARG-10.
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)=0.1 nM) than on Cav2.2/CACNA1B expressed with the ancillary
CC       subunits CACNA2D1 and CACNB3 (IC(50)=19.9 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 an
CC       expression 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}.
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DR   AlphaFoldDB; P0DQD4; -.
DR   SMR; P0DQD4; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR012321; Conotoxin_omega-typ_CS.
DR   PROSITE; PS60004; OMEGA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   Amidation; Calcium channel impairing toxin; Disulfide bond;
KW   Ion channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated calcium channel impairing toxin.
FT   PEPTIDE         1..25
FT                   /note="Omega conotoxin-CVIF"
FT                   /evidence="ECO:0000305|PubMed:19892914"
FT                   /id="PRO_0000446386"
FT   MOD_RES         25
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P05484"
FT   DISULFID        1..16
FT                   /evidence="ECO:0000250|UniProtKB:P05484"
FT   DISULFID        8..20
FT                   /evidence="ECO:0000250|UniProtKB:P05484"
FT   DISULFID        15..25
FT                   /evidence="ECO:0000250|UniProtKB:P05484"
FT   MUTAGEN         10
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"
SQ   SEQUENCE   25 AA;  2672 MW;  F4749E4DCAE3734D CRC64;
     CKGKGASCRR TSYDCCTGSC RLGRC