ID   CM3C_CONSR              Reviewed;          22 AA.
AC   A0A7M4DUE8;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 2.
DT   23-FEB-2022, entry version 4.
DE   RecName: Full=Mu-conotoxin SxIIIC {ECO:0000303|PubMed:33023152};
OS   Conus striolatus (Cone snail).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX   NCBI_TaxID=101315 {ECO:0000312|PDB:6X8R};
RN   [1] {ECO:0000312|PDB:6X8R}
RP   PROTEIN SEQUENCE, SYNTHESIS, STRUCTURE BY NMR, SUBCELLULAR LOCATION, MASS
RP   SPECTROMETRY, DISULFIDE BONDS, AND AMIDATION AT CYS-22.
RC   TISSUE=Venom;
RX   PubMed=33023152; DOI=10.3390/biomedicines8100391;
RA   McMahon K.L., Tran H.N.T., Deuis J.R., Lewis R.J., Vetter I.,
RA   Schroeder C.I.;
RT   "Discovery, pharmacological characterisation and NMR structure of the novel
RT   mu-conotoxin SxIIIC, a potent and irreversible NaV channel inhibitor.";
RL   Biomedicines 8:0-0(2020).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC       toxin potently inhibits hNav1.4/SCN4A (IC(50)=15.11 nM). It also
CC       displays lower activities on other human subtypes (Nav1.1/SCN1A;
CC       IC(50)=132 nM, Nav1.2/SCN2A; IC(50)=363.8, Nav1.3/SCN3A; IC(50)=89.4,
CC       Nav1.6/SCN3A; IC(50)=124.9, Nav1.7/SCN7A; IC(50)=152.2). At
CC       Nav1.7/SCN9A, it does not elicit change in channel voltage-dependence
CC       of fast inactivation or activation, suggesting it acts as a pore
CC       blocker. Interestingly, it blocks current inhibition in an irreversible
CC       manner (tested during 35 minutes). {ECO:0000269|PubMed:33023152}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33023152}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:33023152}.
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   -!- MASS SPECTROMETRY: Mass=2435.78; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:33023152};
CC   -!- MISCELLANEOUS: Does not show activity on hNav1.5/SCN5A and
CC       hNav1.8/SCN10A (tested at 1 uM). {ECO:0000269|PubMed:33023152}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   PDB; 6X8R; NMR; -; A=1-22.
DR   PDBsum; 6X8R; -.
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.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..22
FT                   /note="Mu-conotoxin SxIIIC"
FT                   /evidence="ECO:0000269|PubMed:33023152"
FT                   /id="PRO_0000453397"
FT   MOD_RES         22
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000269|PubMed:33023152"
FT   DISULFID        3..15
FT                   /evidence="ECO:0000269|PubMed:33023152"
FT   DISULFID        4..21
FT                   /evidence="ECO:0000269|PubMed:33023152"
FT   DISULFID        10..22
FT                   /evidence="ECO:0000269|PubMed:33023152"
SQ   SEQUENCE   22 AA;  2444 MW;  3C7280F10E16F532 CRC64;
     RGCCNGRGGC SSRWCRDHAR CC