ID   CM3B_CONST              Reviewed;          20 AA.
AC   P0CE77;
DT   23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 1.
DT   25-MAY-2022, entry version 26.
DE   RecName: Full=Mu-conotoxin SIIIB;
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, FUNCTION, MASS SPECTROMETRY, PYROGLUTAMATE
RP   FORMATION AT GLN-1, AMIDATION AT CYS-20, AND MUTAGENESIS OF GLN-1.
RC   TISSUE=Venom;
RX   PubMed=18522941; DOI=10.1074/jbc.m802852200;
RA   Schroeder C.I., Ekberg J., Nielsen K.J., Adams D., Loughnan M.L.,
RA   Thomas L., Adams D.J., Alewood P.F., Lewis R.J.;
RT   "Neuronally mu-conotoxins from Conus striatus utilize an alpha-helical
RT   motif to target mammalian sodium channels.";
RL   J. Biol. Chem. 283:21621-21628(2008).
RN   [2]
RP   MUTAGENESIS OF GLN-1 AND 1-GLN-ASN-2, AND SYNTHESIS.
RX   PubMed=22733528; DOI=10.1002/bip.22032;
RA   Schroeder C.I., Adams D., Thomas L., Alewood P.F., Lewis R.J.;
RT   "N- and C-terminal extensions of mu-conotoxins increase potency and
RT   selectivity for neuronal sodium channels.";
RL   Biopolymers 98:161-165(2012).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (VGSC).
CC       Potently displaces (125)I-TIIIA from native rat brain Nav1.2/SCN2A
CC       (IC(50) is 5 nM) and muscle Nav1.4/SCN4A (IC(50) is 3 nM) VGSCs.
CC       Potently and irreversibly inhibits current through Xenopus oocyte-
CC       expressed Nav1.2/SCN2A and Nav1.4/SCN4A. {ECO:0000269|PubMed:18522941}.
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=2120.7; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:18522941};
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P0CE77; -.
DR   ConoServer; 1615; SIIIB.
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; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Pyrrolidone carboxylic acid;
KW   Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..20
FT                   /note="Mu-conotoxin SIIIB"
FT                   /id="PRO_0000392728"
FT   MOD_RES         1
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:18522941"
FT   MOD_RES         20
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000269|PubMed:18522941"
FT   DISULFID        3..13
FT                   /evidence="ECO:0000250"
FT   DISULFID        4..19
FT                   /evidence="ECO:0000250"
FT   DISULFID        8..20
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         1..2
FT                   /note="QN->E: Slight decrease in affinity to Nav1.2/SCN2A
FT                   and decrease in affinity to Nav1.4/SCN4A ([N2E]SIIIB(2-
FT                   20))."
FT                   /evidence="ECO:0000269|PubMed:22733528"
FT   MUTAGEN         1
FT                   /note="Q->E: Decrease of affinity to Nav1.2/SCN2A and
FT                   important decrease to Nav1.4/SCN4A with shift of
FT                   selectivity in favor of Nav1.2/SCN2A."
FT                   /evidence="ECO:0000269|PubMed:18522941,
FT                   ECO:0000269|PubMed:22733528"
FT   MUTAGEN         1
FT                   /note="Q->ER: Slight increase of selectivity to
FT                   Nav1.2/SCN2A and slight decrease of affinity to
FT                   Nav1.4/SCN4A."
FT                   /evidence="ECO:0000269|PubMed:18522941,
FT                   ECO:0000269|PubMed:22733528"
FT   MUTAGEN         1
FT                   /note="Q->R: Slight increase of affinity to Nav1.2/SCN2A
FT                   and slight decrease of affinity to Nav1.4/SCN4A."
FT                   /evidence="ECO:0000269|PubMed:18522941,
FT                   ECO:0000269|PubMed:22733528"
FT   MUTAGEN         1
FT                   /note="Missing: Increase of affinity to both Nav1.2/SCN2A
FT                   and Nav1.4/SCN4A."
FT                   /evidence="ECO:0000269|PubMed:18522941,
FT                   ECO:0000269|PubMed:22733528"
SQ   SEQUENCE   20 AA;  2145 MW;  6A4818B24C40BFF9 CRC64;
     QNCCNGGCSS KWCKGHARCC