O16K0_CONTE
ID O16K0_CONTE Reviewed; 78 AA.
AC Q9U655;
DT 08-FEB-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=Delta-conotoxin TxVIA;
DE AltName: Full=Conotoxin King-Kong 0 {ECO:0000303|PubMed:2706261};
DE Short=KK-0 {ECO:0000250|UniProtKB:P18511};
DE AltName: Full=Conotoxin tx6a {ECO:0000303|PubMed:23031820};
DE AltName: Full=TxIA {ECO:0000303|PubMed:1761058, ECO:0000303|PubMed:8261090};
DE AltName: Full=TxMKLT1-0112 {ECO:0000312|EMBL:AAF07972.1};
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].
RC TISSUE=Venom duct;
RX PubMed=11158371; DOI=10.1093/oxfordjournals.molbev.a003786;
RA Conticello S.G., Gilad Y., Avidan N., Ben-Asher E., Levy Z., Fainzilber M.;
RT "Mechanisms for evolving hypervariability: the case of conopeptides.";
RL Mol. Biol. Evol. 18:120-131(2001).
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, TISSUE SPECIFICITY, POSITION IN VENOM
RP DUCT, AND OXIDATION AT MET-59.
RC TISSUE=Venom;
RX PubMed=23031820; DOI=10.1016/j.toxicon.2012.09.013;
RA Dobson R., Collodoro M., Gilles N., Turtoi A., De Pauw E., Quinton L.;
RT "Secretion and maturation of conotoxins in the venom ducts of Conus
RT textile.";
RL Toxicon 60:1370-1379(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. Is present in all duct
CC parts with a highest content in part 4 (distal part near the pharynx).
CC {ECO:0000305|PubMed:1761058, ECO:0000305|PubMed:19380747,
CC ECO:0000305|PubMed:23031820, 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}.
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 for which the
CC structure by NMR has been determined. The cross-references to PDB can
CC be found in entry AC P18511. {ECO:0000305}.
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DR EMBL; AF193261; AAF07972.1; -; mRNA.
DR AlphaFoldDB; Q9U655; -.
DR SMR; Q9U655; -.
DR ConoServer; 1094; TxVIA precursor.
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 Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW 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_0000404710"
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_0000404711"
FT MOD_RES 59
FT /note="Methionine sulfoxide; partial"
FT /evidence="ECO:0000269|PubMed:19380747,
FT ECO:0000269|PubMed:23031820"
FT DISULFID 53..68
FT /evidence="ECO:0000269|PubMed:12145313"
FT DISULFID 60..72
FT /evidence="ECO:0000269|PubMed:12145313"
FT DISULFID 67..77
FT /evidence="ECO:0000269|PubMed:12145313"
SQ SEQUENCE 78 AA; 8722 MW; D1004F9ED066415E CRC64;
MKLTCMMIVA VLFLTAWTFA TADDSGNGLE NLFSNAHHQM KNPEASKLNK RWCKQSGEMC
NLLDQNCCDG YCIVLVCT
