ID   CM3A_CONSR              Reviewed;          22 AA.
AC   P0C8V2;
DT   03-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   25-MAY-2022, entry version 33.
DE   RecName: Full=Mu-conotoxin SxIIIA {ECO:0000303|PubMed:18831583};
OS   Conus striolatus (Cone snail).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX   NCBI_TaxID=101315;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS, FUNCTION, AND AMIDATION AT ALA-22.
RC   TISSUE=Venom duct;
RX   PubMed=18831583; DOI=10.1021/ja804303p;
RA   Walewska A., Skalicky J.J., Davis D.R., Zhang M.-M., Lopez-Vera E.,
RA   Watkins M., Han T.S., Yoshikami D., Olivera B.M., Bulaj G.;
RT   "NMR-based mapping of disulfide bridges in cysteine-rich peptides:
RT   application to the mu-conotoxin SxIIIA.";
RL   J. Am. Chem. Soc. 130:14280-14286(2008).
RN   [2]
RP   FUNCTION, AND SYNTHESIS.
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.
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).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC       synthetic toxin potently blocks rNav1.4/SCN4A (IC(50)= 7 nM). It also
CC       moderately blocks rNav1.1/SCN1A (IC(50)=370 nM), rNav1.2/SCN2A
CC       (IC(50)=1 uM), and mNav1.6/SCN6A (IC(50)=570 nM) (PubMed:18831583,
CC       PubMed:21652775). It is noteworthy that coexpression of subunits beta-2
CC       or beta-4 (but not beta-1 or beta-3) decrease by about 16-fold the
CC       binding potency of the toxin to rNav1.6, since these subunits (thanks
CC       to their extracellular domain) covalently bind to the key cysteine of
CC       the channel, thus preventing the covalent binding of the toxin
CC       (PubMed:25632083). It is also noteworthy that the toxin is 50-fold more
CC       potent on mouse Nav1.6 than on rat Nav1.6 (PubMed:25632083). In vivo,
CC       when injected intraperitoneally or subcutaneously in mice, causes motor
CC       impairment, paralysis and death (PubMed:18831583).
CC       {ECO:0000269|PubMed:18831583, ECO:0000269|PubMed:21652775}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:18831583}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:18831583}.
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. {ECO:0000305}.
CC   -!- TOXIC DOSE: When injected intraperitoneally or subcutaneously in mice,
CC       this toxin causes motor impairment/paralysis and is lethal at doses as
CC       low as 0.6 nmol per mouse. {ECO:0000269|PubMed:18831583}.
CC   -!- MISCELLANEOUS: Does not inhibit rNav1.3/SCN3A, rNav1.5/SCN5A,
CC       rNav1.7/SCN9A and rNav1.8/SCN10A (PubMed:21652775, PubMed:25632083).
CC       {ECO:0000269|PubMed:21652775, ECO:0000269|PubMed:25632083}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P0C8V2; -.
DR   ConoServer; 3584; SxIIIA.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Amidation; Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW   Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..22
FT                   /note="Mu-conotoxin SxIIIA"
FT                   /evidence="ECO:0000305|PubMed:18831583"
FT                   /id="PRO_0000366072"
FT   MOD_RES         22
FT                   /note="Alanine amide"
FT                   /evidence="ECO:0000305|PubMed:18831583"
FT   DISULFID        2..15
FT                   /evidence="ECO:0000250|UniProtKB:P01523,
FT                   ECO:0000305|PubMed:18831583"
FT   DISULFID        3..20
FT                   /evidence="ECO:0000250|UniProtKB:P01523,
FT                   ECO:0000305|PubMed:18831583"
FT   DISULFID        10..21
FT                   /evidence="ECO:0000250|UniProtKB:P01523,
FT                   ECO:0000305|PubMed:18831583"
SQ   SEQUENCE   22 AA;  2278 MW;  0295D34CBFA4861D CRC64;
     RCCTGKKGSC SGRACKNLKC CA