GM3C_CONCN
ID GM3C_CONCN Reviewed; 22 AA.
AC I1SB07;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 25-MAY-2022, entry version 33.
DE RecName: Full=Mu-conotoxin CnIIIC {ECO:0000303|PubMed:22229737};
OS Conus consors (Singed cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=101297;
RN [1]
RP PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, BIOASSAY, PYROGLUTAMATE FORMATION AT
RP GLN-1, MASS SPECTROMETRY, STRUCTURE BY NMR, AND DISULFIDE BONDS.
RC TISSUE=Venom;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PYROGLUTAMATE FORMATION AT GLN-1, AMIDATION AT
RP CYS-22, MASS SPECTROMETRY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom duct;
RX PubMed=22705119; DOI=10.1016/j.jprot.2012.06.001;
RA Violette A., Biass D., Dutertre S., Koua D., Piquemal D., Pierrat F.,
RA Stocklin R., Favreau P.;
RT "Large-scale discovery of conopeptides and conoproteins in the injectable
RT venom of a fish-hunting cone snail using a combined proteomic and
RT transcriptomic approach.";
RL J. Proteomics 75:5215-5225(2012).
RN [3]
RP BIOTECHNOLOGY, AND REVIEW.
RX PubMed=28988749; DOI=10.1016/j.bmc.2017.09.029;
RA Pennington M.W., Czerwinski A., Norton R.S.;
RT "Peptide therapeutics from venom: Current status and potential.";
RL Bioorg. Med. Chem. 26:2738-2758(2018).
CC -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC synthetic toxin blocks both voltage-gated sodium channels and nicotinic
CC acetylcholine receptor (nAChR). Inhibits the skeletal muscle
CC rNav1.4/SCN4A (IC(50)=1.3 nM) and the brain rNav1.2/SCN2A in a long-
CC lasting manner. A low inhibition is also observed on neuronal
CC mNav1.6/SCN8A and mNav1.7/SCN9A. Modestly blocks nAChR alpha-3/beta-2
CC subtype (IC(50)=450 nM) (partially reversible) and, to a lesser extent,
CC alpha-7 and alpha-4/beta-2 subtypes (reversible). In vitro, decreases
CC twitch tension in mouse hemidiaphragms (IC(50)=150 nM), and displays a
CC high blocking effect in mouse extensor digitorum longus muscles
CC (IC(50)=46 nM). {ECO:0000269|PubMed:22229737}.
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 -!- MASS SPECTROMETRY: Mass=2374.10; Method=Electrospray; Note=CnIIIC,
CC monoisotopic.; Evidence={ECO:0000269|PubMed:22229737};
CC -!- MASS SPECTROMETRY: Mass=2373.85; Method=Electrospray; Note=CnIIIC.;
CC Evidence={ECO:0000269|PubMed:22705119};
CC -!- MASS SPECTROMETRY: Mass=2391.00; Method=Electrospray; Note=[Gln1]-
CC CnIIIC.; Evidence={ECO:0000269|PubMed:22705119};
CC -!- BIOTECHNOLOGY: Is commercialized under the name XEP-018 by Activen in
CC the cosmetic area. When applied as a cream, it is claimed to reduce
CC fine-line wrinkles. {ECO:0000305|PubMed:28988749}.
CC -!- MISCELLANEOUS: 1 uM does not block cardiac mNav1.5/SCN5A and DRG-
CC specific rNav1.8/SCN10A channels. 5 uM does not block voltage-gated
CC potassium channels rKv1.1/KCNA1, rKv1.2/KCNA2, hKv1.3/KCNA3,
CC rKv1.4/KCNA4, rKv1.5/KCNA5, rKv1.6/KCNA6, Shaker, hERG1/KCNH2
CC (PubMed:22229737). {ECO:0000305|PubMed:22229737}.
CC -!- MISCELLANEOUS: Found in both injectable (milked) (IV) and dissected
CC venom (DV) (PubMed:22705119 and PubMed:22229737).
CC -!- SIMILARITY: Belongs to the conotoxin M 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 PDB; 2YEN; NMR; -; A=2-22.
DR PDBsum; 2YEN; -.
DR AlphaFoldDB; I1SB07; -.
DR SMR; I1SB07; -.
DR ConoServer; 3834; CnIIIC.
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:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
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 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Postsynaptic neurotoxin; Pyrrolidone carboxylic acid; Secreted;
KW Toxin; Voltage-gated sodium channel impairing toxin.
FT PEPTIDE 1..22
FT /note="Mu-conotoxin CnIIIC"
FT /evidence="ECO:0000269|PubMed:22229737"
FT /id="PRO_0000419876"
FT MOD_RES 1
FT /note="Pyrrolidone carboxylic acid; partial"
FT /evidence="ECO:0000269|PubMed:22229737,
FT ECO:0000269|PubMed:22705119"
FT MOD_RES 22
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:22705119"
FT DISULFID 3..15
FT /evidence="ECO:0000269|PubMed:22229737"
FT DISULFID 4..21
FT /evidence="ECO:0000269|PubMed:22229737"
FT DISULFID 10..22
FT /evidence="ECO:0000269|PubMed:22229737"
FT TURN 3..5
FT /evidence="ECO:0007829|PDB:2YEN"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:2YEN"
FT HELIX 13..18
FT /evidence="ECO:0007829|PDB:2YEN"
SQ SEQUENCE 22 AA; 2400 MW; EA8DBDF10E14979C CRC64;
QGCCNGPKGC SSKWCRDHAR CC
