ID   U6A_CONER               Reviewed;          32 AA.
AC   P60513;
DT   01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2004, sequence version 1.
DT   25-MAY-2022, entry version 83.
DE   RecName: Full=Delta-conotoxin EVIA {ECO:0000303|PubMed:14615484, ECO:0000303|PubMed:14976206};
DE            Short=Delta-EVIA {ECO:0000303|PubMed:14615484, ECO:0000303|PubMed:14976206};
OS   Conus ermineus (Agate cone) (Chelyconus ermineus).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Chelyconus.
OX   NCBI_TaxID=55423;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS
RP   SPECTROMETRY, HYDROXYLATION AT PRO-6, AMIDATION AT LEU-32, AND SYNTHESIS.
RC   TISSUE=Venom;
RX   PubMed=14615484; DOI=10.1074/jbc.m309576200;
RA   Barbier J., Lamthanh H., Le Gall F., Favreau P., Benoit E., Chen H.,
RA   Gilles N., Ilan N., Heinemann S.H., Gordon D., Menez A., Molgo J.;
RT   "A delta-conotoxin from Conus ermineus venom inhibits inactivation in
RT   vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles.";
RL   J. Biol. Chem. 279:4680-4685(2004).
RN   [2]
RP   STRUCTURE BY NMR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, TOXIC DOSE,
RP   DISULFIDE BONDS, SYNTHESIS, AND MUTAGENESIS OF PRO-13.
RC   TISSUE=Venom;
RX   PubMed=14976206; DOI=10.1074/jbc.m309594200;
RA   Volpon L., Lamthanh H., Barbier J., Gilles N., Molgo J., Menez A.,
RA   Lancelin J.-M.;
RT   "NMR solution structures of delta-conotoxin EVIA from Conus ermineus that
RT   selectively acts on vertebrate neuronal Na+ channels.";
RL   J. Biol. Chem. 279:21356-21366(2004).
CC   -!- FUNCTION: Delta-conotoxins bind to site 6 of voltage-gated sodium
CC       channels and inhibit the inactivation process. This toxin inhibits
CC       sodium channel inactivation in neuronal membranes from amphibians and
CC       mammals (Nav1.2a/SCN1A, Nav1.3/SCN3A and Nav1.6/SCN8A) upon binding to
CC       receptor site 6. {ECO:0000269|PubMed:14615484}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14615484,
CC       ECO:0000269|PubMed:14976206}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000269|PubMed:14615484, ECO:0000269|PubMed:14976206}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:14976206, ECO:0000312|PDB:1G1P,
CC       ECO:0000312|PDB:1G1Z}.
CC   -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=3288.3; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:14615484};
CC   -!- TOXIC DOSE: Dose that produces hyperactivity (ED(50)) is 1.8 pmol/g
CC       body mass (native toxin), 1.9 pmol/g body mass (synthetic toxin) and
CC       3.9 pmol/g body mass (P13A mutant). {ECO:0000269|PubMed:14976206}.
CC   -!- MISCELLANEOUS: Does not affect rat skeletal muscle (Nav1.4/SCN4A) and
CC       human cardiac muscle (Nav1.5/SCN5A) sodium channels.
CC       {ECO:0000305|PubMed:14615484}.
CC   -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC       12-Leu-Pro-13. {ECO:0000269|PubMed:14976206}.
CC   -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
CC   -!- CAUTION: Another delta-conotoxin was named EVIA in 2001, but this toxin
CC       was renamed EVIB (AC P69752). {ECO:0000305}.
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DR   PDB; 1G1P; NMR; -; A=1-32.
DR   PDB; 1G1Z; NMR; -; A=1-32.
DR   PDBsum; 1G1P; -.
DR   PDBsum; 1G1Z; -.
DR   AlphaFoldDB; P60513; -.
DR   SMR; P60513; -.
DR   ConoServer; 1561; EVIA.
DR   EvolutionaryTrace; P60513; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR012322; Conotoxin_d-typ_CS.
DR   PROSITE; PS60005; DELTA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW   Hydroxylation; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW   Toxin; Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..32
FT                   /note="Delta-conotoxin EVIA"
FT                   /evidence="ECO:0000269|PubMed:14615484"
FT                   /id="PRO_0000044868"
FT   MOD_RES         6
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:14615484"
FT   MOD_RES         32
FT                   /note="Leucine amide"
FT                   /evidence="ECO:0000269|PubMed:14615484"
FT   DISULFID        3..21
FT                   /evidence="ECO:0000269|PubMed:14976206,
FT                   ECO:0000312|PDB:1G1P, ECO:0000312|PDB:1G1Z"
FT   DISULFID        10..25
FT                   /evidence="ECO:0000269|PubMed:14976206,
FT                   ECO:0000312|PDB:1G1P, ECO:0000312|PDB:1G1Z"
FT   DISULFID        20..29
FT                   /evidence="ECO:0000269|PubMed:14976206,
FT                   ECO:0000312|PDB:1G1P, ECO:0000312|PDB:1G1Z"
FT   MUTAGEN         13
FT                   /note="P->A: 2-fold decrease of activity. Exists only as a
FT                   trans isomer."
FT                   /evidence="ECO:0000269|PubMed:14976206"
FT   STRAND          13..16
FT                   /evidence="ECO:0007829|PDB:1G1P"
FT   STRAND          25..29
FT                   /evidence="ECO:0007829|PDB:1G1P"
SQ   SEQUENCE   32 AA;  3279 MW;  96C544273232D62D CRC64;
     DDCIKPYGFC SLPILKNGLC CSGACVGVCA DL