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 18-SEP-2019, entry version 77. 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 (Atlantic fish-hunting cone). OC Eukaryota; Metazoa; Lophotrochozoa; Mollusca; Gastropoda; OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Chelyconus. OX NCBI_TaxID=55423; RN [1] RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP MASS SPECTROMETRY, HYDROXYLATION AT PRO-6, AMIDATION AT LEU-32, AND RP 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 RT muscles."; RL J. Biol. Chem. 279:4680-4685(2004). RN [2] RP STRUCTURE BY NMR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, TOXIC RP DOSE, 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 RT that 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 CC and mammals (Nav1.2a/SCN1A, Nav1.3/SCN3A and Nav1.6/SCN8A) upon CC binding to 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). CC {ECO:0000305}. CC -!- MASS SPECTROMETRY: Mass=3288.3; Method=Electrospray; Range=1-32; CC Evidence={ECO:0000269|PubMed:14615484}; CC -!- TOXIC DOSE: Dose that produces hyperactivity (ED(50)) is 1.8 CC pmol/g body mass (native toxin), 1.9 pmol/g body mass (synthetic CC toxin) and 3.9 pmol/g body mass (P13A mutant). CC {ECO:0000269|PubMed:14976206}. CC -!- MISCELLANEOUS: Does not affect rat skeletal muscle (Nav1.4/SCN4A) CC and human cardiac muscle (Nav1.5/SCN5A) sodium channels. CC {ECO:0000305|PubMed:14615484}. CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization CC at 12-Leu-Pro-13. {ECO:0000269|PubMed:14976206}. CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. CC {ECO:0000305}. CC -!- CAUTION: Another delta-conotoxin was named EVIA in 2001, but this CC toxin was renamed EVIB (AC P69752). {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR PDB; 1G1P; NMR; -; A=1-32. DR PDB; 1G1Z; NMR; -; A=1-32. DR PDBsum; 1G1P; -. DR PDBsum; 1G1Z; -. 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; KW Secreted; Toxin; Voltage-gated sodium channel impairing toxin. FT PEPTIDE 1 32 Delta-conotoxin EVIA. FT {ECO:0000269|PubMed:14615484}. FT /FTId=PRO_0000044868. FT MOD_RES 6 6 4-hydroxyproline. FT {ECO:0000269|PubMed:14615484}. FT MOD_RES 32 32 Leucine amide. FT {ECO:0000269|PubMed:14615484}. FT DISULFID 3 21 {ECO:0000269|PubMed:14976206, FT ECO:0000312|PDB:1G1P, FT ECO:0000312|PDB:1G1Z}. FT DISULFID 10 25 {ECO:0000269|PubMed:14976206, FT ECO:0000312|PDB:1G1P, FT ECO:0000312|PDB:1G1Z}. FT DISULFID 20 29 {ECO:0000269|PubMed:14976206, FT ECO:0000312|PDB:1G1P, FT ECO:0000312|PDB:1G1Z}. FT MUTAGEN 13 13 P->A: 2-fold decrease of activity. Exists FT only as a trans isomer. FT {ECO:0000269|PubMed:14976206}. FT STRAND 13 16 {ECO:0000244|PDB:1G1P}. FT STRAND 25 29 {ECO:0000244|PDB:1G1P}. SQ SEQUENCE 32 AA; 3279 MW; 96C544273232D62D CRC64; DDCIKPYGFC SLPILKNGLC CSGACVGVCA DL //