CM3B_CONBU
ID CM3B_CONBU Reviewed; 78 AA.
AC C1J5M6;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=Mu-conotoxin BuIIIB {ECO:0000303|PubMed:18950653};
DE AltName: Full=Conotoxin Bu16;
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 51-75, FUNCTION ON SCN4A, AND
RP AMIDATION AT CYS-75.
RC TISSUE=Venom duct;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 26-78.
RC TISSUE=Venom duct;
RX PubMed=21266071; DOI=10.1186/1471-2164-12-60;
RA Hu H., Bandyopadhyay P.K., Olivera B.M., Yandell M.;
RT "Characterization of the Conus bullatus genome and its venom-duct
RT transcriptome.";
RL BMC Genomics 12:60-60(2011).
RN [3]
RP FUNCTION, AND SYNTHESIS OF 52-75.
RX PubMed=21652775; DOI=10.1073/pnas.1107027108;
RA Wilson M.J., Yoshikami D., Azam L., Gajewiak J., Olivera B.M., Bulaj G.,
RA Zhang M.M.;
RT "mu-Conotoxins that differentially block sodium channels Nav1.1 through 1.8
RT identify those responsible for action potentials in sciatic nerve.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10302-10307(2011).
RN [4]
RP FUNCTION, AND SYNTHESIS OF 52-75.
RX PubMed=25632083; DOI=10.1152/jn.01004.2014;
RA Wilson M.J., Zhang M.M., Gajewiak J., Azam L., Rivier J.E., Olivera B.M.,
RA Yoshikami D.;
RT "Alpha- and beta-subunit composition of voltage-gated sodium channels
RT investigated with mu-conotoxins and the recently discovered muO'section
RT sign'-conotoxin GVIIJ.";
RL J. Neurophysiol. 113:2289-2301(2015).
RN [5]
RP STRUCTURE BY NMR OF 52-75, SYNTHESIS OF 52-75, MUTAGENESIS OF VAL-52;
RP GLY-53; GLU-54; ARG-55 AND 52-VAL--ARG-55, FUNCTION ON SCN3A, AND DISULFIDE
RP BONDS.
RX PubMed=23557677; DOI=10.1021/cb300674x;
RA Kuang Z., Zhang M.-M., Gupta K., Gajewiak J., Gulyas J., Balaram P.,
RA Rivier J.E., Olivera B.M., Yoshikami D., Bulaj G., Norton R.S.;
RT "Mammalian neuronal sodium channel blocker mu-conotoxin BuIIIB has a
RT structured N-terminus that influences potency.";
RL ACS Chem. Biol. 8:1344-1351(2013).
CC -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC synthetic toxin potently blocks rNav1.4/SCN4A (Kd=0.34-3.6 nM),
CC rNav1.2/SCN2A (Kd=13 nM), rNav1.3/SCN3A (Kd=200 nM), rNav1.1/SCN1A
CC (Kd=360 nM), mNav1.6/SCN8A (IC(50)=1.8 uM), rNav1.5/SCN5A (IC(50)=9
CC uM), rNav1.6/SCN8A (IC(50)>30 uM) (PubMed:18950653, PubMed:21652775,
CC PubMed:25632083, PubMed:23557677). It is noteworthy that the toxin is
CC 50-fold more potent on mouse Nav1.6 than on rat Nav1.6
CC (PubMed:25632083). The block of SCN4A is very slowly reversible
CC (PubMed:18950653). {ECO:0000269|PubMed:18950653,
CC ECO:0000269|PubMed:21652775, ECO:0000269|PubMed:23557677,
CC ECO:0000269|PubMed:25632083}.
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: Does not or very weakly inhibits rNav1.7 and rNav1.8.
CC {ECO:0000269|PubMed:21652775, ECO:0000269|PubMed:23557677}.
CC -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR EMBL; FJ240166; ACO50771.1; -; mRNA.
DR PDB; 2LO9; NMR; -; A=52-75.
DR PDB; 2LOC; NMR; -; A=52-75.
DR PDBsum; 2LO9; -.
DR PDBsum; 2LOC; -.
DR AlphaFoldDB; C1J5M6; -.
DR BMRB; C1J5M6; -.
DR SMR; C1J5M6; -.
DR ConoServer; 3715; BuIIIB 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_0000384433"
FT PEPTIDE 52..75
FT /note="Mu-conotoxin BuIIIB"
FT /evidence="ECO:0000305|PubMed:18950653"
FT /id="PRO_0000384434"
FT REGION 26..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 75
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:18950653"
FT DISULFID 56..68
FT /evidence="ECO:0000269|PubMed:23557677,
FT ECO:0000312|PDB:2LO9, ECO:0000312|PDB:2LOC"
FT DISULFID 57..74
FT /evidence="ECO:0000269|PubMed:23557677,
FT ECO:0000312|PDB:2LO9, ECO:0000312|PDB:2LOC"
FT DISULFID 64..75
FT /evidence="ECO:0000269|PubMed:23557677,
FT ECO:0000312|PDB:2LO9, ECO:0000312|PDB:2LOC"
FT MUTAGEN 52..55
FT /note="Missing: 4-fold increase in blocking SCN3A (K(d) is
FT 53 nM)."
FT /evidence="ECO:0000269|PubMed:23557677"
FT MUTAGEN 52
FT /note="V->A: 3.5-decrease in blocking SCN3A (K(d) is 710
FT nM)."
FT /evidence="ECO:0000269|PubMed:23557677"
FT MUTAGEN 53
FT /note="G->A: 5-fold increase in blocking SCN3A (K(d) is 36
FT nM)."
FT /evidence="ECO:0000269|PubMed:23557677"
FT MUTAGEN 53
FT /note="G->A: Mutated into D-Ala. 40-fold increase in
FT blocking SCN3A (K(d) is 4.8 nM)."
FT /evidence="ECO:0000269|PubMed:23557677"
FT MUTAGEN 54
FT /note="E->A: 13-fold increase in blocking SCN3A (K(d) is 15
FT nM)."
FT /evidence="ECO:0000269|PubMed:23557677"
FT MUTAGEN 55
FT /note="R->A: No change in blocking SCN3A (K(d) is 118 nM)."
FT /evidence="ECO:0000269|PubMed:23557677"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:2LO9"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:2LO9"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:2LO9"
FT HELIX 66..71
FT /evidence="ECO:0007829|PDB:2LO9"
SQ SEQUENCE 78 AA; 8877 MW; 907D09C9B4DE3164 CRC64;
MMSKLGVLLT ICLLLFPLFA LPQDGDQPAD RPAERMQDDI SSEQNPLLEK RVGERCCKNG
KRGCGRWCRD HSRCCGRR
