ID   CM3C_CONBU              Reviewed;          80 AA.
AC   C1J5M7;
DT   22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT   26-MAY-2009, sequence version 1.
DT   25-MAY-2022, entry version 36.
DE   RecName: Full=Mu-conotoxin BuIIIC {ECO:0000303|PubMed:18950653};
DE   Flags: Precursor;
OS   Conus bullatus (Bubble cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Textilia.
OX   NCBI_TaxID=89438;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 52-77, FUNCTION, AND AMIDATION AT
RP   CYS-77.
RX   PubMed=18950653; DOI=10.1016/j.toxicon.2008.10.017;
RA   Holford M., Zhang M.-M., Gowd K.H., Azam L., Green B.R., Watkins M.,
RA   Ownby J.-P., Yoshikami D., Bulaj G., Olivera B.M.;
RT   "Pruning nature: biodiversity-derived discovery of novel sodium channel
RT   blocking conotoxins from Conus bullatus.";
RL   Toxicon 53:90-98(2009).
RN   [2]
RP   STRUCTURE BY NMR OF MUTANT R2-MIDI BUIIIC, FUNCTION OF MUTANT R2-MIDI
RP   BUIIIC, MUTAGENESIS OF 64-ARG-GLY-65 AND CYS-70, AND DISULFIDE BOND OF
RP   MUTANT R2-MIDI BUIIIC.
RX   PubMed=22773842; DOI=10.1074/jbc.m112.375733;
RA   Stevens M., Peigneur S., Dyubankova N., Lescrinier E., Herdewijn P.,
RA   Tytgat J.;
RT   "Design of bioactive peptides from naturally occurring mu-conotoxin
RT   structures.";
RL   J. Biol. Chem. 287:31382-31392(2012).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels. Extremely
CC       potent inhibitor of Nav1.4/SCN4A (96% inhibition at 1 uM). The
CC       inhibition is very slowly reversible. {ECO:0000269|PubMed:18950653}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:18950653}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:18950653}.
CC   -!- DOMAIN: The cysteine framework is III (CC-C-C-CC). Classified in the M-
CC       5 branch, since 5 residues stand between the fourth and the fifth
CC       cysteine residues. {ECO:0000305}.
CC   -!- MISCELLANEOUS: Potent inhibitor of Nav1.2/SCN2A (IC(50)=34.1 nM)
CC       (PubMed:22773842). Also inhibits Nav1.3/SCN3A (10% inhibition at 75
CC       nM), Nav1.4/SCN4A (45% inhibition at 75 nM), Nav1.6/SCN8A (45%
CC       inhibition at 75 nM), but does not inhibit Nav1.5/SCN5A and
CC       Nav1.8/SCN10A (75 nM tested) (PubMed:22773842). The inhibition is
CC       slowly reversible (PubMed:22773842). {ECO:0000269|PubMed:22773842}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   EMBL; FJ240167; ACO50772.1; -; mRNA.
DR   PDB; 2LU6; NMR; -; 1=66-77.
DR   PDBsum; 2LU6; -.
DR   AlphaFoldDB; C1J5M7; -.
DR   BMRB; C1J5M7; -.
DR   SMR; C1J5M7; -.
DR   PRIDE; C1J5M7; -.
DR   ConoServer; 3714; BuIIIC precursor.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR004214; Conotoxin.
DR   Pfam; PF02950; Conotoxin; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin; Secreted; Signal;
KW   Toxin; Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..51
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000384435"
FT   PEPTIDE         52..77
FT                   /note="Mu-conotoxin BuIIIC"
FT                   /evidence="ECO:0000305|PubMed:18950653"
FT                   /id="PRO_0000384436"
FT   MOD_RES         77
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000305|PubMed:18950653"
FT   DISULFID        56..70
FT                   /evidence="ECO:0000250|UniProtKB:C1J5M6"
FT   DISULFID        57..76
FT                   /evidence="ECO:0000250|UniProtKB:C1J5M6"
FT   DISULFID        66..77
FT                   /evidence="ECO:0000250|UniProtKB:C1J5M6"
FT   MUTAGEN         52..63
FT                   /note="Missing: In R2-Midi BuIIIC; potently and selectively
FT                   inhibits Nav1.2/SCN2A."
FT                   /evidence="ECO:0000269|PubMed:22773842"
FT   MUTAGEN         64..65
FT                   /note="RG->CN: In R2-Midi BuIIIC; potently and selectively
FT                   inhibits Nav1.2/SCN2A."
FT                   /evidence="ECO:0000269|PubMed:22773842"
FT   MUTAGEN         70
FT                   /note="C->A: In R2-Midi BuIIIC; potently and selectively
FT                   inhibits Nav1.2/SCN2A."
FT                   /evidence="ECO:0000269|PubMed:22773842"
SQ   SEQUENCE   80 AA;  9178 MW;  2B10B52B191AE1D8 CRC64;
     MMSKLGVLLT ICLLLFPLFA LPQDGDQPAD RPAERMQDDL SSEQHPLFEK RIVDRCCNKG
     NGKRGCSRWC RDHSRCCGRR