ID   CM3C_CONST              Reviewed;          22 AA.
AC   P0C349;
DT   29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   29-MAY-2007, sequence version 1.
DT   25-MAY-2022, entry version 36.
DE   RecName: Full=Mu-conotoxin SIIIC {ECO:0000305};
DE   AltName: Full=Mu-conotoxin TIIIA-like {ECO:0000303|PubMed:17142296};
OS   Conus striatus (Striated cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX   NCBI_TaxID=6493;
RN   [1]
RP   PROTEIN SEQUENCE, SYNTHESIS, HYDROXYLATION AT PRO-8 AND PRO-18, STRUCTURE
RP   BY NMR, DISULFIDE BONDS, AND MUTAGENESIS OF HIS-2; LYS-6; LYS-9; ARG-14;
RP   GLU-15; ARG-17; GLN-19 AND HIS-20.
RC   TISSUE=Venom;
RX   PubMed=17142296; DOI=10.1124/mol.106.028225;
RA   Lewis R.J., Schroeder C.I., Ekberg J., Nielsen K.J., Loughnan M.,
RA   Thomas L., Adams D.A., Drinkwater R., Adams D.J., Alewood P.F.;
RT   "Isolation and structure-activity of mu-conotoxin TIIIA, a potent inhibitor
RT   of tetrodotoxin-sensitive voltage-gated sodium channels.";
RL   Mol. Pharmacol. 71:676-685(2007).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels. This
CC       synthetic peptide reversibly inhibits the brain sodium channel
CC       rNav1.2/SCN2A (IC(50) is 40 nM) and the skeletal muscle sodium channel
CC       rNav1.4/SCN4A (IC(50) is 9 nM).
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       4 branch, since 4 residues stand between the fourth and the fifth
CC       cysteine residues.
CC   -!- MISCELLANEOUS: No cis-trans isomerization is found.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P0C349; -.
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   Pfam; PF05374; Mu-conotoxin; 1.
PE   1: Evidence at protein level;
KW   Amidation; Direct protein sequencing; Disulfide bond; Hydroxylation;
KW   Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..22
FT                   /note="Mu-conotoxin SIIIC"
FT                   /id="PRO_0000288944"
FT   SITE            14
FT                   /note="Important for activity"
FT   MOD_RES         8
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MOD_RES         18
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MOD_RES         22
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P0C350"
FT   DISULFID        4..16
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   DISULFID        5..21
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   DISULFID        11..22
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         2
FT                   /note="H->A: Slight increase in toxicity at rat muscle."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         6
FT                   /note="K->A,Q: Little decrease in toxicity at both rat
FT                   muscle and brain level."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         9
FT                   /note="K->A,Q: Little decrease in toxicity at both rat
FT                   muscle and brain level."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         14
FT                   /note="R->A,Y,Q: Important decrease of toxicity at both rat
FT                   muscle and brain level."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         15
FT                   /note="E->A: 10-fold increase in affinity for both rat
FT                   brain and muscle Navs."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         17
FT                   /note="R->A,Q: Little decrease in toxicity at both rat
FT                   muscle and brain level."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         19
FT                   /note="Q->A: Slight increase in toxicity at rat muscle."
FT                   /evidence="ECO:0000269|PubMed:17142296"
FT   MUTAGEN         20
FT                   /note="H->A: Little decrease in toxicity at both rat muscle
FT                   and brain level."
FT                   /evidence="ECO:0000269|PubMed:17142296"
SQ   SEQUENCE   22 AA;  2433 MW;  DE2CFD292B88B11C CRC64;
     RHGCCKGPKG CSSRECRPQH CC