CKBR_CONSL
ID CKBR_CONSL Reviewed; 103 AA.
AC P0CG46;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Conantokin-Br {ECO:0000303|PubMed:19309162};
DE Short=Con-Br {ECO:0000303|PubMed:19309162};
DE Short=ConBr {ECO:0000305};
DE AltName: Full=Conantoxin-S1 {ECO:0000303|PubMed:17153339};
DE Short=Con-S1 {ECO:0000303|PubMed:17153339};
DE Flags: Precursor;
OS Conus sulcatus (Sulcate cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Asprella.
OX NCBI_TaxID=101760;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 80-103, FUNCTION, MUTAGENESIS OF
RP 87-PHE-ILE-88; 84-TYR-SER-85 AND TYR-84, SITE, MOLECULAR MODELING, AND
RP GAMMA-CARBOXYGLUTAMATION AT GLU-82; GLU-83; GLU-89 AND GLU-93.
RC STRAIN=Conus sulcatus brettingham; TISSUE=Venom duct;
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).
RN [2]
RP NOMENCLATURE.
RX PubMed=17153339; DOI=10.1007/978-3-540-30880-5_4;
RA Franco A., Pisarewicz K., Moller C., Mora D., Fields G.B., Mari F.;
RT "Hyperhydroxylation: a new strategy for neuronal targeting by venomous
RT marine molluscs.";
RL Prog. Mol. Subcell. Biol. 43:83-103(2006).
CC -!- FUNCTION: Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors.
CC This toxin inhibits NR2 subunits N-methyl-D-aspartate (NMDA) receptor-
CC mediated calcium influx in central nervous system neurons in the
CC following order of preference: NR2B/GRIN2B (IC(50)=0.14 uM),
CC NR2D/GRIN2D (IC(50)=0.31 uM), NR2A/GRIN2A (IC(50)=0.68 uM) and
CC NR2C/GRIN2A (IC(50)=4.9 uM), when tested on rat receptors.
CC {ECO:0000269|PubMed:19309162}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P58806};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P58806};
CC Note=Divalent cations stabilize the toxin the in alpha-helix
CC conformation. {ECO:0000250|UniProtKB:P58806};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.
CC -!- MISCELLANEOUS: The mature peptide does not contain cysteine residue.
CC -!- SIMILARITY: Belongs to the conotoxin B superfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0CG46; -.
DR SMR; P0CG46; -.
DR ConoServer; 4202; Conantokin-Su 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.
PE 1: Evidence at protein level;
KW Calcium; 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..21
FT /evidence="ECO:0000255"
FT PROPEP 22..79
FT /evidence="ECO:0000305|PubMed:19309162"
FT /id="PRO_0000395614"
FT PEPTIDE 80..103
FT /note="Conantokin-Br"
FT /evidence="ECO:0000305|PubMed:19309162"
FT /id="PRO_0000395615"
FT REGION 34..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 89
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 93
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 84
FT /note="Significant for the subtype selectivity between
FT NR2B/GRIN2B and NR2D/GRIN2D (similar potency for both of
FT them)"
FT /evidence="ECO:0000305|PubMed:19309162"
FT MOD_RES 82
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07231,
FT ECO:0000305|PubMed:19309162"
FT MOD_RES 83
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07231,
FT ECO:0000305|PubMed:19309162"
FT MOD_RES 89
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07231,
FT ECO:0000305|PubMed:19309162"
FT MOD_RES 93
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P07231,
FT ECO:0000305|PubMed:19309162"
FT MUTAGEN 84..85
FT /note="YS->VA: 37-fold decrease in potency for NR2B/GRIN2B
FT with a relative increase in selectivity for this subunit;
FT complete decrease in potency for NR2D/GRIN2D."
FT /evidence="ECO:0000269|PubMed:19309162"
FT MUTAGEN 84
FT /note="Y->V: 23-fold decrease in potency for NR2B/GRIN2B
FT with a relative increase in selectivity for this subunit;
FT complete decrease in potency for NR2D/GRIN2D."
FT /evidence="ECO:0000269|PubMed:19309162"
FT MUTAGEN 87..88
FT /note="FI->MAA: Important decrease in potency for
FT NR2B/GRIN2B; complete decrease in potency for NR2D/GRIN2D."
FT /evidence="ECO:0000269|PubMed:19309162"
SQ SEQUENCE 103 AA; 11708 MW; 76FF2E398C94C894 CRC64;
MQLYTYLYLL VPLVTFHLIL GTGTLDHGGA LTERRSTDAT ALKPEPVLQK SAARSTDDNG
KDRLTQMKRI LKKRGKNARG DEEYSKFIER EREAGRLDLS KFP
