ID   O16A_CONTE              Reviewed;          78 AA.
AC   P18511;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 1.
DT   22-FEB-2023, entry version 108.
DE   RecName: Full=Delta-conotoxin TxVIA {ECO:0000303|PubMed:12145313, ECO:0000303|PubMed:8300586};
DE   AltName: Full=Conotoxin King-Kong 0 {ECO:0000303|PubMed:2706261};
DE            Short=KK-0 {ECO:0000312|EMBL:CAA37377.1};
DE   AltName: Full=TxIA {ECO:0000303|PubMed:1761058, ECO:0000303|PubMed:8261090};
DE   Flags: Precursor;
OS   Conus textile (Cloth-of-gold cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX   NCBI_TaxID=6494;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1691090; DOI=10.1002/j.1460-2075.1990.tb08204.x;
RA   Woodward S.R., Cruz L.J., Olivera B.M., Hillyard D.R.;
RT   "Constant and hypervariable regions in conotoxin propeptides.";
RL   EMBO J. 9:1015-1020(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 49-78, PROTEIN SEQUENCE OF 52-78, SUBCELLULAR
RP   LOCATION, AND FUNCTION.
RC   TISSUE=Venom;
RX   PubMed=2706261; DOI=10.1021/bi00427a049;
RA   Hillyard D.R., Olivera B.M., Woodward S.R., Corpuz G.P., Gray W.R.,
RA   Ramilo C.A., Cruz L.J.;
RT   "A molluscivorous Conus toxin: conserved frameworks in conotoxins.";
RL   Biochemistry 28:358-361(1989).
RN   [3]
RP   PROTEIN SEQUENCE OF 52-78, AND SUBCELLULAR LOCATION.
RC   STRAIN=Neovicarius; TISSUE=Venom;
RX   PubMed=1761058; DOI=10.1111/j.1432-1033.1991.tb16412.x;
RA   Fainzilber M., Gordon D., Hasson A., Spira M.E., Zlotkin E.;
RT   "Mollusc-specific toxins from the venom of Conus textile neovicarius.";
RL   Eur. J. Biochem. 202:589-595(1991).
RN   [4]
RP   PROTEIN SEQUENCE OF 52-78, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP   OXIDATION AT MET-59.
RC   TISSUE=Venom;
RX   PubMed=19380747; DOI=10.1073/pnas.0900745106;
RA   Ueberheide B.M., Fenyo D., Alewood P.F., Chait B.T.;
RT   "Rapid sensitive analysis of cysteine rich peptide venom components.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:6910-6915(2009).
RN   [5]
RP   FUNCTION.
RX   PubMed=8261090; DOI=10.1111/j.1460-9568.1993.tb00205.x;
RA   Hasson A., Fainzilber M., Gordon D., Zlotkin E., Spira M.E.;
RT   "Alteration of sodium currents by new peptide toxins from the venom of a
RT   molluscivorous Conus snail.";
RL   Eur. J. Neurosci. 5:56-64(1993).
RN   [6]
RP   FUNCTION.
RX   PubMed=8300586; DOI=10.1016/s0021-9258(17)41983-1;
RA   Fainzilber M., Kofman O., Zlotkin E., Gordon D.;
RT   "A new neurotoxin receptor site on sodium channels is identified by a
RT   conotoxin that affects sodium channel inactivation in molluscs and acts as
RT   an antagonist in rat brain.";
RL   J. Biol. Chem. 269:2574-2580(1994).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=22709442; DOI=10.1021/pr300312h;
RA   Bhatia S., Kil Y.J., Ueberheide B., Chait B.T., Tayo L., Cruz L., Lu B.,
RA   Yates J.R. III, Bern M.;
RT   "Constrained de novo sequencing of conotoxins.";
RL   J. Proteome Res. 11:4191-4200(2012).
RN   [8]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=12145313; DOI=10.1074/jbc.m206833200;
RA   Kohno T., Sasaki T., Kobayashi K., Fainzilber M., Sato K.;
RT   "Three-dimensional solution structure of the sodium channel
RT   agonist/antagonist delta-conotoxin TxVIA.";
RL   J. Biol. Chem. 277:36387-36391(2002).
CC   -!- FUNCTION: Delta-conotoxins bind to site 6 of voltage-gated sodium
CC       channels (Nav) and inhibit the inactivation process. Binding of this
CC       toxin is strongly calcium-dependent but not voltage-dependent. The
CC       binding site is most likely on the extracellular side of the sodium
CC       channel. Binds receptor sites on both mollusk and rat central nervous
CC       system, but despite its high affinity binding to rat sodium channel, it
CC       has no functional effect in vivo and in vitro on it. Has also no effect
CC       on Gambusia fish. Is important in mollusk for the paralysis of the
CC       prey. Upon injection of the peptide, a subordinate lobster assumes an
CC       exaggerated dominant posture (of a 'King-Kong' lobster!).
CC       {ECO:0000269|PubMed:1761058, ECO:0000269|PubMed:2706261,
CC       ECO:0000269|PubMed:8261090, ECO:0000269|PubMed:8300586}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1761058,
CC       ECO:0000269|PubMed:19380747, ECO:0000269|PubMed:2706261}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:1761058, ECO:0000305|PubMed:19380747,
CC       ECO:0000305|PubMed:2706261}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:12145313, ECO:0000269|PubMed:19380747}.
CC   -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=3034.2; Mass_error=0.05; Method=Electrospray;
CC       Note=Without oxidation at Met-59.;
CC       Evidence={ECO:0000269|PubMed:19380747};
CC   -!- MASS SPECTROMETRY: Mass=3050.189; Mass_error=0.05; Method=Electrospray;
CC       Note=With oxidation at Met-59.; Evidence={ECO:0000269|PubMed:19380747};
CC   -!- MISCELLANEOUS: Veratridine increases the rate of dissociation in a
CC       dose-dependent manner.
CC   -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
CC   -!- CAUTION: Several genes are coding for this toxin, it is therefore also
CC       shown in entry AC Q9U655. {ECO:0000305}.
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DR   EMBL; X53283; CAA37377.1; -; mRNA.
DR   PIR; S12513; S12513.
DR   PDB; 1FU3; NMR; -; A=52-78.
DR   PDBsum; 1FU3; -.
DR   AlphaFoldDB; P18511; -.
DR   SMR; P18511; -.
DR   TCDB; 8.B.4.1.7; the conotoxin t (conotoxin t) family.
DR   ConoServer; 598; TxVIA precursor.
DR   EvolutionaryTrace; P18511; -.
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   SUPFAM; SSF57059; omega toxin-like; 1.
DR   PROSITE; PS60005; DELTA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Knottin; Neurotoxin; Oxidation; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..49
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000034900"
FT   PEPTIDE         52..78
FT                   /note="Delta-conotoxin TxVIA"
FT                   /evidence="ECO:0000269|PubMed:1761058,
FT                   ECO:0000269|PubMed:19380747, ECO:0000269|PubMed:2706261"
FT                   /id="PRO_0000034901"
FT   MOD_RES         59
FT                   /note="Methionine sulfoxide; partial"
FT                   /evidence="ECO:0000269|PubMed:19380747"
FT   DISULFID        53..68
FT                   /evidence="ECO:0000269|PubMed:12145313,
FT                   ECO:0000312|PDB:1FU3"
FT   DISULFID        60..72
FT                   /evidence="ECO:0000269|PubMed:12145313,
FT                   ECO:0000312|PDB:1FU3"
FT   DISULFID        67..77
FT                   /evidence="ECO:0000269|PubMed:12145313,
FT                   ECO:0000312|PDB:1FU3"
FT   STRAND          62..64
FT                   /evidence="ECO:0007829|PDB:1FU3"
FT   STRAND          67..70
FT                   /evidence="ECO:0007829|PDB:1FU3"
SQ   SEQUENCE   78 AA;  8760 MW;  C5CBFD462AD40A35 CRC64;
     MKLTCMMIVA VLFLTAWTFA TADDPRNGLG NLFSNAHHEM KNPEASKLNK RWCKQSGEMC
     NLLDQNCCDG YCIVLVCT
//