ID   O16D_CONCT              Reviewed;          73 AA.
AC   P58920;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   26-JUL-2002, sequence version 1.
DT   25-MAY-2022, entry version 72.
DE   RecName: Full=Omega-conotoxin CVID {ECO:0000303|PubMed:10938268};
DE   AltName: Full=AM-336;
DE            Short=AM336 {ECO:0000303|PubMed:10938268};
DE   AltName: Full=CNSB004;
DE   AltName: Full=Leconotide;
DE   Flags: Precursor;
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], PROTEIN SEQUENCE OF 46-72, AMIDATION AT CYS-72,
RP   SYNTHESIS OF 46-72, STRUCTURE BY NMR OF 46-72, DISULFIDE BOND, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom, and Venom duct;
RX   PubMed=10938268; DOI=10.1074/jbc.m002252200;
RA   Lewis R.J., Nielsen K.J., Craik D.J., Loughnan M.L., Adams D.A.,
RA   Sharpe I.A., Luchian T., Adams D.J., Bond T., Thomas L., Jones A.,
RA   Matheson J.-L., Drinkwater R., Andrews P.R., Alewood P.F.;
RT   "Novel omega-conotoxins from Conus catus discriminate among neuronal
RT   calcium channel subtypes.";
RL   J. Biol. Chem. 275:35335-35344(2000).
RN   [2]
RP   FUNCTION, MUTAGENESIS OF LYS-55 AND TYR-58, AND STRUCTURE BY NMR OF 46-72.
RX   PubMed=12441339; DOI=10.1074/jbc.m209969200;
RA   Adams D.J., Smith A.B., Schroeder C.I., Yasuda T., Lewis R.J.;
RT   "Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-
RT   sensitive calcium channel associated with transmitter release from
RT   preganglionic nerve terminals.";
RL   J. Biol. Chem. 278:4057-4062(2003).
CC   -!- FUNCTION: Omega-conotoxins act at presynaptic membranes, they bind and
CC       block voltage-gated calcium channels. This toxin inhibits
CC       neurotransmitter release, it blocks N-type calcium channels, probably a
CC       N-type (Cav2.2/CACNA1B) calcium channel variant.
CC       {ECO:0000269|PubMed:12441339}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10938268}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:10938268}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:10938268}.
CC   -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC   -!- PHARMACEUTICAL: Is under phase I clinical trial under the name AM336 by
CC       Amrad Corporation Limited for treating severe morphine-resistant pain
CC       stress.
CC   -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P58920; -.
DR   SMR; P58920; -.
DR   ConoServer; 1569; CVID precursor.
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; 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; Calcium channel impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW   Pharmaceutical; Presynaptic neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated calcium channel impairing toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..45
FT                   /evidence="ECO:0000269|PubMed:10938268"
FT                   /id="PRO_0000034964"
FT   PEPTIDE         46..72
FT                   /note="Omega-conotoxin CVID"
FT                   /id="PRO_0000034965"
FT   SITE            58
FT                   /note="Important for calcium channel binding"
FT   MOD_RES         72
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000269|PubMed:10938268"
FT   DISULFID        46..61
FT                   /evidence="ECO:0000269|PubMed:10938268"
FT   DISULFID        53..65
FT                   /evidence="ECO:0000269|PubMed:10938268"
FT   DISULFID        60..72
FT                   /evidence="ECO:0000269|PubMed:10938268"
FT   MUTAGEN         55
FT                   /note="K->R: 20% reduction of neurotransmitter release."
FT                   /evidence="ECO:0000269|PubMed:12441339"
FT   MUTAGEN         58
FT                   /note="Y->F: No activity on neurotransmitter release."
FT                   /evidence="ECO:0000269|PubMed:12441339"
SQ   SEQUENCE   73 AA;  7748 MW;  C4CEBD30C77DAEC3 CRC64;
     MKLTCVVIVA VLLLTACQLI TADDSRGTQK HRALRSDTKL SMSTRCKSKG AKCSKLMYDC
     CSGSCSGTVG RCG