ID   CM3A_CONTS              Reviewed;          67 AA.
AC   H2BKS9;
DT   12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2012, sequence version 1.
DT   25-MAY-2022, entry version 24.
DE   RecName: Full=Mu-conotoxin TsIIIA {ECO:0000303|PubMed:28219625};
DE   Flags: Precursor;
OS   Conus tessulatus (Tessellate cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Tesselliconus.
OX   NCBI_TaxID=101317;
RN   [1] {ECO:0000312|EMBL:AEX60400.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=24080356; DOI=10.1016/j.toxicon.2013.09.020;
RA   Zhou M., Wang L., Wu Y., Zhu X., Feng Y., Chen Z., Li Y., Sun D., Ren Z.,
RA   Xu A.;
RT   "Characterizing the evolution and functions of the M-superfamily
RT   conotoxins.";
RL   Toxicon 76:150-159(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SYNTHESIS OF 49-67.
RC   TISSUE=Venom duct;
RX   PubMed=28219625; DOI=10.1016/j.toxicon.2017.02.013;
RA   Yang M., Zhao S., Min X., Shao M., Chen Y., Chen Z., Zhou M.;
RT   "A novel mu-conotoxin from worm-hunting Conus tessulatus that selectively
RT   inhibit rat TTX-resistant sodium currents.";
RL   Toxicon 130:11-18(2017).
RN   [3]
RP   FUNCTION, AND SYNTHESIS OF 49-67.
RX   PubMed=32758497; DOI=10.1016/j.toxicon.2020.07.024;
RA   Yang M., Zhou M.;
RT   "Mu-conotoxin TsIIIA, a peptide inhibitor of human voltage-gated sodium
RT   channel hNav1.8.";
RL   Toxicon 186:29-34(2020).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC       toxin specifically inhibits mammalian Nav1.8/SCN10A sodium currents
CC       (IC(50)=2.11 uM) without inducing a shift in the current-voltage
CC       relationship of this channel (PubMed:32758497). In vivo, shows potent
CC       analgesic activity in a mice hotplate analgesic assay
CC       (PubMed:28219625). In addition, this toxin has better analgesic effects
CC       than Ziconotide, an analgesic drug (PubMed:28219625).
CC       {ECO:0000269|PubMed:28219625, ECO:0000269|PubMed:32758497}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:24080356,
CC       ECO:0000305|PubMed:28219625}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:24080356, ECO:0000305|PubMed:28219625}.
CC   -!- DOMAIN: The cysteine framework is III (CC-C-C-CC). Classified in the M-
CC       4 branch, since 5 residues stand between the fourth and the fifth
CC       cysteine residues. {ECO:0000305}.
CC   -!- MISCELLANEOUS: Has no effects (10 uM tested) on the human tetrodotoxin-
CC       sensitive Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A,
CC       Nav1.6/SCN8A and Nav1.7/SCN9A, as well as human tetrodotoxin-resistant
CC       Nav1.5/SCN7A. {ECO:0000269|PubMed:32758497}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   EMBL; JF510914; AEX60400.1; -; mRNA.
DR   AlphaFoldDB; H2BKS9; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR004214; Conotoxin.
DR   Pfam; PF02950; Conotoxin; 1.
PE   3: Inferred from homology;
KW   Cleavage on pair of basic residues; Disulfide bond;
KW   Ion channel impairing toxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..48
FT                   /evidence="ECO:0000305|PubMed:28219625"
FT                   /id="PRO_0000439628"
FT   PEPTIDE         49..67
FT                   /note="Mu-conotoxin TsIIIA"
FT                   /evidence="ECO:0000305|PubMed:28219625"
FT                   /id="PRO_5003560264"
FT   DISULFID        50..59
FT                   /evidence="ECO:0000250|UniProtKB:P01523,
FT                   ECO:0000305|PubMed:28219625"
FT   DISULFID        51..64
FT                   /evidence="ECO:0000250|UniProtKB:P01523,
FT                   ECO:0000305|PubMed:28219625"
FT   DISULFID        55..65
FT                   /evidence="ECO:0000250|UniProtKB:P01523,
FT                   ECO:0000305|PubMed:28219625"
SQ   SEQUENCE   67 AA;  7463 MW;  206AFF70D78B15E1 CRC64;
     MMSKLGVLLT ICLLLFPLTA VPLDGDQPAD QPAERKQNEQ HPLFDQKRGC CRWPCPSRCG
     MARCCSS