CKR_CONRA
ID CKR_CONRA Reviewed; 107 AA.
AC P58806;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Conantokin-R {ECO:0000303|PubMed:10604979, ECO:0000303|PubMed:10734223};
DE Short=Con-R {ECO:0000303|PubMed:10604979, ECO:0000303|PubMed:10734223};
DE Flags: Precursor;
OS Conus radiatus (Rayed cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Phasmoconus.
OX NCBI_TaxID=61198;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=12350383; DOI=10.1016/s0920-1211(02)00101-8;
RA Jimenez E.C., Donevan S., Walker C., Zhou L.-M., Nielsen J., Cruz L.J.,
RA Armstrong H., White H.S., Olivera B.M.;
RT "Conantokin-L, a new NMDA receptor antagonist: determinants for
RT anticonvulsant potency.";
RL Epilepsy Res. 51:73-80(2002).
RN [2]
RP PROTEIN SEQUENCE OF 81-107, GAMMA-CARBOXYGLUTAMATION AT GLU-83; GLU-84;
RP GLU-91 AND GLU-95, FUNCTION, SYNTHESIS OF 81-107, MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, AND DISULFIDE BOND.
RC TISSUE=Venom;
RX PubMed=10604979;
RA White H.S., McCabe R.T., Armstrong H., Donevan S.D., Cruz L.J.,
RA Abogadie F.C., Torres J., Rivier J.E., Paarmann I., Hollmann M.,
RA Olivera B.M.;
RT "In vitro and in vivo characterization of conantokin-R, a selective NMDA
RT receptor antagonist isolated from the venom of the fish-hunting snail Conus
RT radiatus.";
RL J. Pharmacol. Exp. Ther. 292:425-432(2000).
RN [3]
RP SYNTHESIS OF 81-107, METAL-BINDING, AND COFACTOR.
RX PubMed=10734223; DOI=10.1016/s0014-5793(00)01309-0;
RA Blandl T., Warder S.E., Prorok M., Castellino F.J.;
RT "Structure-function relationships of the NMDA receptor antagonist peptide,
RT conantokin-R.";
RL FEBS Lett. 470:139-146(2000).
RN [4]
RP MUTAGENESIS OF VAL-85, AND SITE.
RX 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 peptides
RT partially governs subunit-selective antagonism of recombinant N-methyl-D-
RT aspartate receptors.";
RL J. Biol. Chem. 276:26860-26867(2001).
RN [5]
RP SYNTHESIS OF 81-107, MUTAGENESIS OF 88-MET--ALA-90; 85-VAL--ALA-86 AND
RP VAL-85, AND SITE.
RC STRAIN=Conus sulcatus brettinghami;
RX PubMed=19309162; DOI=10.1021/bi802259a;
RA Twede V.D., Teichert R.W., Walker C.S., Gruszczynski P., Kazmierkiewicz R.,
RA Bulaj G., Olivera B.M.;
RT "Conantokin-Br from Conus brettinghami and selectivity determinants for the
RT NR2D subunit of the NMDA receptor.";
RL Biochemistry 48:4063-4073(2009).
CC -!- FUNCTION: Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors.
CC This toxin is potent in the following order of preference: NR2B
CC approximately NR2A/GRIN2A > NR2C/GRIN2C >> NR2D/GRIN2D. Induces sleep-
CC like symptoms in young mice. Is a highly potent anticonvulsant
CC compound. {ECO:0000269|PubMed:10604979}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:10734223};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10734223};
CC Note=Divalent cations stabilize the toxin the in alpha-helix
CC conformation. Zinc also stabilizes the alpha-helical conformation.
CC {ECO:0000269|PubMed:10734223};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10604979}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:10604979}.
CC -!- DOMAIN: The cysteine framework is C-C. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=3098; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:10604979};
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC 106-Tyr-Pro-107.
CC -!- SIMILARITY: Belongs to the conotoxin B superfamily. {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 AlphaFoldDB; P58806; -.
DR ConoServer; 1375; Conantokin-R precursor.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR005918; Conantokin_CS.
DR Pfam; PF10550; Toxin_36; 1.
DR PROSITE; PS60025; CONANTOKIN; 1.
PE 1: Evidence at protein level;
KW Calcium; Direct protein sequencing; Disulfide bond;
KW Gamma-carboxyglutamic acid; Ion channel impairing toxin;
KW Ionotropic glutamate receptor inhibitor; Magnesium; Metal-binding;
KW Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..80
FT /evidence="ECO:0000269|PubMed:10604979"
FT /id="PRO_0000035064"
FT PEPTIDE 81..107
FT /note="Conantokin-R"
FT /evidence="ECO:0000269|PubMed:10604979"
FT /id="PRO_0000035065"
FT REGION 26..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 91
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /note="via 4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07231"
FT BINDING 95
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /note="via 4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07231"
FT SITE 85
FT /note="Significant for the subtype selectivity between
FT NR2B/GRIN2B and NR2D/GRIN2D (potent for NR2B/GRIN2B but not
FT for NR2D/GRIN2D)"
FT MOD_RES 83
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000269|PubMed:10604979"
FT MOD_RES 84
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000269|PubMed:10604979"
FT MOD_RES 91
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000269|PubMed:10604979"
FT MOD_RES 95
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000269|PubMed:10604979"
FT DISULFID 101..105
FT /evidence="ECO:0000269|PubMed:10604979"
FT MUTAGEN 85..86
FT /note="VA->YS: No change in potency for NR2B/GRIN2B; 3-fold
FT increase in potency for NR2D/GRIN2D."
FT /evidence="ECO:0000269|PubMed:19309162"
FT MUTAGEN 85
FT /note="V->I: Little decrease in potency for NR2B; little
FT decrease in potency for NR2A."
FT /evidence="ECO:0000269|PubMed:11335724,
FT ECO:0000269|PubMed:19309162"
FT MUTAGEN 85
FT /note="V->L: No change in potency for NR2B; No change in
FT potency for NR2A."
FT /evidence="ECO:0000269|PubMed:11335724,
FT ECO:0000269|PubMed:19309162"
FT MUTAGEN 85
FT /note="V->Y: Little increase in potency for NR2B; little
FT increase in potency for NR2A."
FT /evidence="ECO:0000269|PubMed:11335724,
FT ECO:0000269|PubMed:19309162"
FT MUTAGEN 85
FT /note="V->Y: No change in potency for NR2B/GRIN2B; 3-fold
FT increase in potency for NR2D/GRIN2D."
FT /evidence="ECO:0000269|PubMed:11335724,
FT ECO:0000269|PubMed:19309162"
FT MUTAGEN 88..90
FT /note="MAA->FI: Important decrease in potency for
FT NR2B/GRIN2B; complete loss in potency for NR2D/GRIN2D."
FT /evidence="ECO:0000269|PubMed:19309162"
SQ SEQUENCE 107 AA; 11834 MW; 8C9BD6E9C83C4B78 CRC64;
MQLYTYLYLL VSLVTFYLIL GTGTLGHGGA LTERRSTDAT ALKPEPVLLQ KSSARSTDDN
GNDRLTQMKR ILKKRGNKAR GEEEVAKMAA ELARENIAKG CKVNCYP
