ID   CKR1C_CONRO             Reviewed;          96 AA.
AC   P0DKZ1;
DT   03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 1.
DT   03-AUG-2022, entry version 21.
DE   RecName: Full=Conantokin Rl-C {ECO:0000305};
DE            Short=Con Rl-C {ECO:0000305};
DE            Short=ConRl-C {ECO:0000303|PubMed:22594498};
DE   Flags: Precursor; Fragment;
OS   Conus rolani (Cone snail).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Asprella.
OX   NCBI_TaxID=745791;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], SYNTHESIS OF 79-96, FUNCTION,
RP   GAMMA-CARBOXYGLUTAMATION AT GLU-81; GLU-82; GLU-85; GLU-89 AND GLU-93, AND
RP   AMIDATION AT ASN-96.
RX   PubMed=22594498; DOI=10.1021/bi300055n;
RA   Gowd K.H., Han T.S., Twede V., Gajewiak J., Smith M.D., Watkins M.,
RA   Platt R.J., Toledo G., White H.S., Olivera B.M., Bulaj G.;
RT   "Conantokins derived from the Asprella clade impart conRl-B, an N-methyl d-
RT   aspartate receptor antagonist with a unique selectivity profile for NR2B
RT   subunits.";
RL   Biochemistry 51:4685-4692(2012).
CC   -!- FUNCTION: Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors.
CC       This toxin has antagonist activity on NR2B/GRIN2B (IC(50)=1.4 uM) and
CC       NR2A/GRIN2A (IC(50)=2.9 uM) subunits, when tested on rat receptors.
CC       {ECO:0000269|PubMed:22594498}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P07231};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P07231};
CC       Note=Divalent cations stabilize the toxin the in alpha-helix
CC       conformation. {ECO:0000250|UniProtKB:P07231};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:22594498}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:22594498}.
CC   -!- MISCELLANEOUS: The mature peptide does not contain cysteine residue.
CC       {ECO:0000305}.
CC   -!- MISCELLANEOUS: Has no antagonist activity on NR2C/GRIN2C, and
CC       NR2D/GRIN2D subunits. {ECO:0000305|PubMed:22594498}.
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; P0DKZ1; -.
DR   ConoServer; 5850; Conantokin-Rl3 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   PROSITE; PS60025; CONANTOKIN; 1.
PE   1: Evidence at protein level;
KW   Amidation; Calcium; Gamma-carboxyglutamic acid;
KW   Ion channel impairing toxin; Ionotropic glutamate receptor inhibitor;
KW   Magnesium; Metal-binding; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..78
FT                   /evidence="ECO:0000305|PubMed:22594498"
FT                   /id="PRO_0000421896"
FT   PEPTIDE         79..96
FT                   /note="Conantokin Rl-C"
FT                   /evidence="ECO:0000305|PubMed:22594498"
FT                   /id="PRO_0000421897"
FT   REGION          36..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         81
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         85
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         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   MOD_RES         81
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P07231,
FT                   ECO:0000305|PubMed:22594498"
FT   MOD_RES         82
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P07231,
FT                   ECO:0000305|PubMed:22594498"
FT   MOD_RES         85
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P07231,
FT                   ECO:0000305|PubMed:22594498"
FT   MOD_RES         89
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P07231,
FT                   ECO:0000305|PubMed:22594498"
FT   MOD_RES         93
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P07231,
FT                   ECO:0000305|PubMed:22594498"
FT   MOD_RES         96
FT                   /note="Asparagine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P07231,
FT                   ECO:0000305|PubMed:22594498"
FT   NON_TER         96
SQ   SEQUENCE   96 AA;  10864 MW;  37B5511265166809 CRC64;
     MQLYTYLYLL VPLVTFHLIL GTGTLDHGDA LTERRSADAT ALKPEPVLLQ KSSARSTDDN
     GKDTQMKRIF KKRRNKARGE EELSENAVEF ARELAN