ID   O16A_CONGL              Reviewed;          77 AA.
AC   Q9TWM7;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 2.
DT   25-MAY-2022, entry version 65.
DE   RecName: Full=Delta-conotoxin GmVIA {ECO:0000303|PubMed:7918355};
DE   Flags: Precursor;
OS   Conus gloriamaris (Glory-of-the-Sea cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX   NCBI_TaxID=37336;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RA   Hillyard D.R., Mcintosh M.J., Jones R.M., Cartier E.G., Watkins M.,
RA   Olivera B.M., Layer R.T.;
RT   "O-superfamily conotoxin peptides.";
RL   Patent number JP2003533178, 11-NOV-2003.
RN   [2]
RP   PROTEIN SEQUENCE OF 49-77, DISULFIDE BOND, SYNTHESIS OF 49-77, MASS
RP   SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=7918355; DOI=10.1021/bi00204a003;
RA   Shon K.-J., Hasson A., Spira M.E., Cruz L.J., Gray W.R., Olivera B.M.;
RT   "Delta-conotoxin GmVIA, a novel peptide from the venom of Conus
RT   gloriamaris.";
RL   Biochemistry 33:11420-11425(1994).
RN   [3]
RP   FUNCTION.
RX   PubMed=7608772; DOI=10.1152/jn.1995.73.3.1295;
RA   Hasson A., Shon K.-J., Olivera B.M., Spira M.E.;
RT   "Alterations of voltage-activated sodium current by a novel conotoxin from
RT   the venom of Conus gloriamaris.";
RL   J. Neurophysiol. 73:1295-1301(1995).
RN   [4]
RP   FUNCTION.
RX   PubMed=10627583; DOI=10.1523/jneurosci.20-01-00076.2000;
RA   Safo P., Rosenbaum T., Shcherbatko A., Choi D.-Y., Han E.,
RA   Toledo-Aral J.J., Olivera B.M., Brehm P., Mandel G.;
RT   "Distinction among neuronal subtypes of voltage-activated sodium channels
RT   by mu-conotoxin PIIIA.";
RL   J. Neurosci. 20:76-80(2000).
CC   -!- FUNCTION: Delta-conotoxins bind to site 6 of voltage-gated sodium
CC       channels (Nav) and inhibit the inactivation process. This toxin shows
CC       weak activity on rNav1.2/SCN2A (EC(50)=2.5 uM) and rNav1.4/SCN4A
CC       (EC(50)=4.8 uM) (PubMed:10627583). In vivo, injection of this peptide
CC       in the head region of garden snail induces retraction of the head and
CC       body into shell. This is followed by secretion of viscous green slime
CC       and a convulsive undulation into and out of the shell. No apparent
CC       biological activity was observed when a much greater dose of peptide
CC       was injected intraperitoneally into mice. {ECO:0000269|PubMed:7608772}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7918355}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:7918355}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:7918355}.
CC   -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=3352.5; Method=LSI;
CC       Evidence={ECO:0000269|PubMed:7918355};
CC   -!- MISCELLANEOUS: This toxin does not show effect on hNav1.7/SCN9A.
CC       {ECO:0000269|PubMed:10627583}.
CC   -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR   EMBL; DJ379385; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR   PIR; A55891; A55891.
DR   AlphaFoldDB; Q9TWM7; -.
DR   SMR; Q9TWM7; -.
DR   ConoServer; 1598; GmVIA.
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; IPR004214; Conotoxin.
DR   InterPro; IPR012322; Conotoxin_d-typ_CS.
DR   Pfam; PF02950; Conotoxin; 1.
DR   PROSITE; PS60005; DELTA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Knottin; Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..48
FT                   /evidence="ECO:0000269|PubMed:7918355"
FT                   /id="PRO_0000392699"
FT   PEPTIDE         49..77
FT                   /note="Delta-conotoxin GmVIA"
FT                   /evidence="ECO:0000269|PubMed:7918355"
FT                   /id="PRO_0000044472"
FT   DISULFID        52..67
FT                   /evidence="ECO:0000269|PubMed:7918355"
FT   DISULFID        59..72
FT                   /evidence="ECO:0000269|PubMed:7918355"
FT   DISULFID        66..76
FT                   /evidence="ECO:0000269|PubMed:7918355"
SQ   SEQUENCE   77 AA;  8705 MW;  3C8389EDAE017B49 CRC64;
     MKLTCMMIVA VLFLTAWTFV TADDSGNGME ILFPKAGHEM ENLEVSNRVK PCRKEGQLCD
     PIFQNCCRGW NCVLFCV