ID   CM3C_CONGE              Reviewed;          22 AA.
AC   P05482;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   25-MAY-2022, entry version 88.
DE   RecName: Full=Mu-conotoxin GIIIC {ECO:0000303|PubMed:2410412};
OS   Conus geographus (Geography cone) (Nubecula geographus).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium.
OX   NCBI_TaxID=6491;
RN   [1]
RP   PROTEIN SEQUENCE, HYDROXYLATION AT PRO-6; PRO-7 AND PRO-17, AMIDATION AT
RP   ALA-22, AND SUBCELLULAR LOCATION.
RX   PubMed=2410412; DOI=10.1016/s0021-9258(17)39364-x;
RA   Cruz L.J., Gray W.R., Olivera B.M., Zeikus R.D., Kerr L., Yoshikami D.,
RA   Moczydlowski E.;
RT   "Conus geographus toxins that discriminate between neuronal and muscle
RT   sodium channels.";
RL   J. Biol. Chem. 260:9280-9288(1985).
RN   [2]
RP   STRUCTURE BY NMR, FUNCTION, DISULFIDE BOND, AND SYNTHESIS.
RX   PubMed=30360356; DOI=10.3390/molecules23102715;
RA   Harvey P.J., Kurniawan N.D., Finol-Urdaneta R.K., McArthur J.R.,
RA   Van Lysebetten D., Dash T.S., Hill J.M., Adams D.J., Durek T., Craik D.J.;
RT   "NMR Structure of mu-conotoxin GIIIC: leucine 18 induces local repacking of
RT   the N-terminus resulting in reduced Nav channel potency.";
RL   Molecules 23:0-0(2018).
CC   -!- FUNCTION: Mu-conotoxins block voltage-gated sodium channels (Nav). This
CC       toxin shows potent activity on Nav1.4/SCN4A (IC(50)=286 nM), and weak
CC       activity on mNav1.6/SCN8A. {ECO:0000269|PubMed:30360356}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2410412}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:2410412}.
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   -!- MISCELLANEOUS: Does not show activity when tested (1 uM) on
CC       rNav1.2/SCN2A, hNav1.5/SCN7A, hNav1.7/SCN9A and hNav1.8/ SCN10A.
CC       {ECO:0000269|PubMed:30360356}.
CC   -!- MISCELLANEOUS: Both the Thr-5-hydroxypro-6 and Lys-16-hydroxypro-17
CC       peptide bonds are in trans conformations, whereas the hydroxypro-6-
CC       hydroxypro-7 bond adopts a cis conformation.
CC       {ECO:0000305|PubMed:30360356}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   PIR; C23579; MXKN3.
DR   PDB; 6MJD; NMR; -; A=1-22.
DR   PDBsum; 6MJD; -.
DR   AlphaFoldDB; P05482; -.
DR   BMRB; P05482; -.
DR   SMR; P05482; -.
DR   ConoServer; 1744; GIIIC.
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.
DR   PROSITE; PS60013; MU_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW   Hydroxylation; Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..22
FT                   /note="Mu-conotoxin GIIIC"
FT                   /evidence="ECO:0000269|PubMed:2410412"
FT                   /id="PRO_0000044495"
FT   SITE            18
FT                   /note="Increases tethering of the N-terminus (compared to
FT                   GIIIA), forming a more compact structure; as a consequence,
FT                   the interaction with Nav1.4/SCN4A is affected and the toxin
FT                   potency is lower than that of GIIIA"
FT                   /evidence="ECO:0000305|PubMed:30360356"
FT   MOD_RES         6
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:2410412"
FT   MOD_RES         7
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:2410412"
FT   MOD_RES         17
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:2410412"
FT   MOD_RES         22
FT                   /note="Alanine amide"
FT                   /evidence="ECO:0000269|PubMed:2410412"
FT   DISULFID        3..15
FT                   /evidence="ECO:0000269|PubMed:30360356,
FT                   ECO:0007744|PDB:6MJD"
FT   DISULFID        4..20
FT                   /evidence="ECO:0000269|PubMed:30360356,
FT                   ECO:0007744|PDB:6MJD"
FT   DISULFID        10..21
FT                   /evidence="ECO:0000269|PubMed:30360356,
FT                   ECO:0007744|PDB:6MJD"
FT   TURN            6..8
FT                   /evidence="ECO:0007829|PDB:6MJD"
FT   HELIX           13..15
FT                   /evidence="ECO:0007829|PDB:6MJD"
SQ   SEQUENCE   22 AA;  2553 MW;  F50402BA92A9813C CRC64;
     RDCCTPPKKC KDRRCKPLKC CA