ID   CXKT_CONTU              Reviewed;          21 AA.
AC   P17684;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   22-JUL-2008, entry version 54.
DE   RecName: Full=Conantokin-T;
DE            Short=Con-T;
OS   Conus tulipa (Fish-hunting cone snail) (Tulip cone).
OC   Eukaryota; Metazoa; Mollusca; Gastropoda; Orthogastropoda;
OC   Apogastropoda; Caenogastropoda; Sorbeoconcha; Hypsogastropoda;
OC   Neogastropoda; Conoidea; Conidae; Conus.
OX   NCBI_TaxID=6495;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Venom;
RX   MEDLINE=90202866; PubMed=2180939;
RA   Haack J.A., Rivier J.E., Parks T.N., Mena E.E., Cruz L.J.,
RA   Olivera B.M.;
RT   "Conantokin-T. A gamma-carboxyglutamate containing peptide with N-
RT   methyl-D-aspartate antagonist activity.";
RL   J. Biol. Chem. 265:6025-6029(1990).
RN   [2]
RP   FUNCTION.
RX   MEDLINE=90327072; PubMed=2165278;
RA   Olivera B.M., Rivier J., Clark C., Ramilo C.A., Corpuz G.P.,
RA   Abogadie F.C., Mena E.E., Woodward S.R., Hillyard D.R., Cruz L.J.;
RT   "Diversity of Conus neuropeptides.";
RL   Science 249:257-263(1990).
RN   [3]
RP   MUTAGENESIS OF TYR-5.
RX   MEDLINE=21347894; PubMed=11335724; DOI=10.1074/jbc.M102428200;
RA   Klein R.C., Prorok M., Galdzicki Z., Castellino F.J.;
RT   "The amino acid residue at sequence position 5 in the conantokin
RT   peptides partially governs subunit-selective antagonism of recombinant
RT   N-methyl-D-aspartate receptors.";
RL   J. Biol. Chem. 276:26860-26867(2001).
RN   [4]
RP   THERAPEUTIC USAGE.
RX   PubMed=12507705; DOI=10.1016/S0304-3959(02)00303-2;
RA   Malmberg A.B., Gilbert H., McCabe R.T., Basbaum A.I.;
RT   "Powerful antinociceptive effects of the cone snail venom-derived
RT   subtype-selective NMDA receptor antagonists conantokins G and T.";
RL   Pain 101:109-116(2003).
RN   [5]
RP   STRUCTURE BY NMR.
RX   MEDLINE=97388301; PubMed=9247135; DOI=10.1016/S0014-5793(97)00573-5;
RA   Warder S.E., Chen Z., Zhu Y., Prorok M., Castellino F.J., Ni F.;
RT   "The NMR solution structure of the NMDA receptor antagonist,
RT   conantokin-T, in the absence of divalent metal ions.";
RL   FEBS Lett. 411:19-26(1997).
RN   [6]
RP   STRUCTURE BY NMR.
RX   MEDLINE=97153002; PubMed=8999936; DOI=10.1074/jbc.272.4.2291;
RA   Skjaerbaek N., Nielsen K.J., Lewis R.J., Alewood P.F., Craik D.J.;
RT   "Determination of the solution structures of conantokin-G and
RT   conantokin-T by CD and NMR spectroscopy.";
RL   J. Biol. Chem. 272:2291-2299(1997).
CC   -!- FUNCTION: Inhibits both NR2A and NR2B subunits of N-methyl-D-
CC       aspartate (NMDA) receptor-mediated calcium influx in central
CC       nervous system neurons. Induces sleep-like symptoms in young mice
CC       and hyperactivity in older mice.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC   -!- PHARMACEUTICAL: Is under phase II clinical trial by Cognetix Inc.
CC       Has potent antinociceptive effects in several models of injury-
CC       induced pain.
CC   -!- SIMILARITY: Belongs to the conantokin family.
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DR   PIR; A35225; A35225.
DR   PDB; 1ONT; NMR; -; A=1-21.
DR   PDBsum; 1ONT; -.
DR   InterPro; IPR005918; Conantokin_CS.
DR   PROSITE; PS60025; CONANTOKIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Calcium; Direct protein sequencing;
KW   Gamma-carboxyglutamic acid; Pharmaceutical; Secreted; Toxin.
FT   PEPTIDE       1     21       Conantokin-T.
FT                                /FTId=PRO_0000044504.
FT   SITE          5      5       Important for selectivity.
FT   MOD_RES       3      3       4-carboxyglutamate.
FT   MOD_RES       4      4       4-carboxyglutamate.
FT   MOD_RES      10     10       4-carboxyglutamate.
FT   MOD_RES      14     14       4-carboxyglutamate.
FT   MOD_RES      21     21       Alanine amide.
FT   MUTAGEN       5      5       Y->F: No loss of inhibition of NR1a/NR2B
FT                                receptor; little loss of inhibition of
FT                                NR1a/NR2A receptor.
FT   MUTAGEN       5      5       Y->V: Little loss of inhibition of
FT                                NR1a/NR2B receptor; important loss of
FT                                inhibition of NR1a/NR2A receptor.
FT   MUTAGEN       5      5       Y->W: Little loss of inhibition of
FT                                NR1a/NR2B receptor; complete loss of
FT                                inhibition of NR1a/NR2A receptor.
FT   HELIX         2     15
FT   HELIX        17     20
SQ   SEQUENCE   21 AA;  2509 MW;  7F7B893AC4842C38 CRC64;
     GEEEYQKMLE NLREAEVKKN A
//