CM3A_CONSE
ID CM3A_CONSE Reviewed; 31 AA.
AC P60207;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 1.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Mu-conotoxin SmIIIA {ECO:0000303|PubMed:12484778};
DE Flags: Precursor; Fragment;
OS Conus stercusmuscarum (Fly-specked cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=89452;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION ON TTX-RESISTANT SODIUM CHANNELS,
RP SYNTHESIS OF 7-28, AND SYNTHESIS OF 8-28.
RC TISSUE=Venom duct;
RX PubMed=12484778; DOI=10.1021/bi0265628;
RA West P.J., Bulaj G., Garrett J.E., Olivera B.M., Yoshikami D.;
RT "Mu-conotoxin SmIIIA, a potent inhibitor of tetrodotoxin-resistant sodium
RT channels in amphibian sympathetic and sensory neurons.";
RL Biochemistry 41:15388-15393(2002).
RN [2]
RP FUNCTION ON SODIUM CHANNELS, AND SYNTHESIS OF 7-28.
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 [3]
RP FUNCTION, AND SYNTHESIS OF 7-28.
RX PubMed=22229737; DOI=10.1111/j.1476-5381.2012.01837.x;
RA Favreau P., Benoit E., Hocking H.G., Carlier L., D'Hoedt D., Leipold E.,
RA Markgraf R., Schlumberger S., Cordova M.A., Gaertner H.,
RA Paolini-Bertrand M., Hartley O., Tytgat J., Heinemann S.H., Bertrand D.,
RA Boelens R., Stocklin R., Molgo J.;
RT "A novel u-conopeptide, CnIIIC, exerts potent and preferential inhibition
RT of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine
RT receptors.";
RL Br. J. Pharmacol. 166:1654-1668(2012).
RN [4]
RP FUNCTION ON SODIUM CHANNELS, AND SYNTHESIS OF 7-28.
RX PubMed=23146020; DOI=10.1111/bph.12051;
RA Zhang M.M., Wilson M.J., Azam L., Gajewiak J., Rivier J.E., Bulaj G.,
RA Olivera B.M., Yoshikami D.;
RT "Co-expression of Na(V)beta subunits alters the kinetics of inhibition of
RT voltage-gated sodium channels by pore-blocking mu-conotoxins.";
RL Br. J. Pharmacol. 168:1597-1610(2013).
RN [5]
RP STRUCTURE BY NMR OF 7-28, PYROGLUTAMATE FORMATION AT GLN-7, AMIDATION AT
RP CYS-28, SYNTHESIS OF 7-28, AND DISULFIDE BONDS.
RX PubMed=12970353; DOI=10.1074/jbc.m309222200;
RA Keizer D.W., West P.J., Lee E.F., Yoshikami D., Olivera B.M., Bulaj G.,
RA Norton R.S.;
RT "Structural basis for tetrodotoxin-resistant sodium channel binding by mu-
RT conotoxin SmIIIA.";
RL J. Biol. Chem. 278:46805-46813(2003).
CC -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC toxin blocks rNav1.5/SCN5A (IC(50) is 1.3 uM), rNav1.6/SCN8A (IC(50) is
CC 160 nM), rNav1.7/SCN9A (IC(50) is 1.3 uM), rNav1.1/SCN1A (K(d) is 3.8
CC nM), rNav1.2/SCN2A (K(d) is 1.3 nM), rNav1.4/SCN4A (K(d) is 0.22 nM),
CC rNav1.6/SCN8A (K(d) is 69 nM), and rNav1.7/SCN9A (K(d) is 260 nM). This
CC toxin is very potent but weakly discriminating among sodium channels.
CC The block of these channels is modified when beta-subunits are
CC coexpressed with alpha subunits. Hence, blocks of channels containing
CC beta-1 and beta-3 subunits are more potent (compared to channels
CC without beta subunits), whereas blocks of channels containing beta-2
CC and beta-4 subunits are less potent (compared to channels without beta
CC subunits). {ECO:0000269|PubMed:12484778, ECO:0000269|PubMed:21652775,
CC ECO:0000269|PubMed:22229737, ECO:0000269|PubMed:23146020}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
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.
CC -!- PTM: SmIIIA' is a putative isoform where the N-terminal AA is missing.
CC -!- MISCELLANEOUS: All peptide bonds in this toxin adopt the trans
CC conformation. {ECO:0000305|PubMed:12970353}.
CC -!- MISCELLANEOUS: Does not show activity on rNav1.8/SCN10A (IC(50) is >10
CC uM). {ECO:0000305|PubMed:21652775}.
CC -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Biological Magnetic Resonance Data Bank; Note=Mu-
CC conotoxin SmIIIA entry;
CC URL="http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=5881";
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DR PDB; 1Q2J; NMR; -; A=8-28.
DR PDBsum; 1Q2J; -.
DR AlphaFoldDB; P60207; -.
DR SMR; P60207; -.
DR ConoServer; 1629; SmIIIA precursor.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR008036; Conotoxin_mu-typ.
DR PROSITE; PS60013; MU_CONOTOXIN; 1.
PE 2: Evidence at transcript level;
KW 3D-structure; Amidation; Cleavage on pair of basic residues;
KW Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW Pyrrolidone carboxylic acid; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT PROPEP <1..6
FT /evidence="ECO:0000305"
FT /id="PRO_0000035055"
FT PEPTIDE 7..28
FT /note="Mu-conotoxin SmIIIA"
FT /evidence="ECO:0000305|PubMed:12970353"
FT /id="PRO_0000035056"
FT MOD_RES 7
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000305|PubMed:12970353"
FT MOD_RES 28
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:12970353"
FT DISULFID 9..21
FT /evidence="ECO:0000269|PubMed:12970353"
FT DISULFID 10..27
FT /evidence="ECO:0000269|PubMed:12970353"
FT DISULFID 16..28
FT /evidence="ECO:0000269|PubMed:12970353"
FT NON_TER 1
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:1Q2J"
FT STRAND 18..26
FT /evidence="ECO:0007829|PDB:1Q2J"
SQ SEQUENCE 31 AA; 3756 MW; 1F130E7A8FA85EFC CRC64;
PLFDKRQRCC NGRRGCSSRW CRDHSRCCGR R
