ID   CA1_CONMA               Reviewed;          14 AA.
AC   P01521;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   25-MAY-2022, entry version 80.
DE   RecName: Full=Alpha-conotoxin MI {ECO:0000303|PubMed:10529206};
DE            Short=Alpha-MI {ECO:0000303|PubMed:10529206};
DE            Short=CtxMI;
DE   AltName: Full=M1;
OS   Conus magus (Magical cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX   NCBI_TaxID=6492;
RN   [1]
RP   PROTEIN SEQUENCE, AMIDATION AT CYS-14, AND SUBCELLULAR LOCATION.
RX   PubMed=7149738; DOI=10.1016/0003-9861(82)90351-4;
RA   McIntosh J.M., Cruz L.J., Hunkapiller M.W., Gray W.R., Olivera B.M.;
RT   "Isolation and structure of a peptide toxin from the marine snail Conus
RT   magus.";
RL   Arch. Biochem. Biophys. 218:329-334(1982).
RN   [2]
RP   DISULFIDE BONDS.
RX   PubMed=6630187; DOI=10.1016/s0021-9258(17)44165-2;
RA   Gray W.R., Rivier J.E., Galyean R., Cruz L.J., Olivera B.M.;
RT   "Conotoxin MI. Disulfide bonding and conformational states.";
RL   J. Biol. Chem. 258:12247-12251(1983).
RN   [3]
RP   FUNCTION, SYNTHESIS, AND MUTAGENESIS OF ARG-2; HIS-5; PRO-6; LYS-10;
RP   ASN-11; TYR-12 AND SER-13.
RX   PubMed=10529206; DOI=10.1021/bi9907476;
RA   Jacobsen R.B., DelaCruz R.G., Grose J.H., McIntosh J.M., Yoshikami D.,
RA   Olivera B.M.;
RT   "Critical residues influence the affinity and selectivity of alpha-
RT   conotoxin MI for nicotinic acetylcholine receptors.";
RL   Biochemistry 38:13310-13315(1999).
CC   -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC       the nicotinic acetylcholine receptors (nAChR) and thus inhibit them
CC       (PubMed:10529206). Specifically blocks mammalian nAChR at the alpha-
CC       1/delta binding site (PubMed:10529206). Shows very low potency in
CC       blocking the alpha-1/gamma binding site (PubMed:10529206).
CC       {ECO:0000269|PubMed:10529206}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7149738}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:7149738}.
CC   -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha3/5 pattern.
CC       {ECO:0000305}.
CC   -!- PTM: Amidated; synthetic peptide with a C-terminus free is 6-fold less
CC       active than the amidated peptide. {ECO:0000269|PubMed:10529206}.
CC   -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR   PIR; A01784; NTKN1M.
DR   ConoServer; 23; MI.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR   GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR018072; Conotoxin_a-typ_CS.
DR   PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   Acetylcholine receptor inhibiting toxin; Amidation;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Postsynaptic neurotoxin; Secreted; Toxin.
FT   PEPTIDE         1..14
FT                   /note="Alpha-conotoxin MI"
FT                   /evidence="ECO:0000269|PubMed:7149738"
FT                   /id="PRO_0000044461"
FT   MOD_RES         14
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000269|PubMed:7149738"
FT   DISULFID        3..8
FT                   /evidence="ECO:0000269|PubMed:6630187"
FT   DISULFID        4..14
FT                   /evidence="ECO:0000269|PubMed:6630187"
FT   MUTAGEN         2
FT                   /note="R->A: 4-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         5
FT                   /note="H->A: 3-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         6
FT                   /note="P->A: 73-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         10
FT                   /note="K->A: 9-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         11
FT                   /note="N->A: 3-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         12
FT                   /note="Y->A: 8500-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         12
FT                   /note="Y->H: 33-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         12
FT                   /note="Y->M: 48-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         12
FT                   /note="Y->W: 5-fold loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
FT   MUTAGEN         13
FT                   /note="S->A: No loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10529206"
SQ   SEQUENCE   14 AA;  1499 MW;  DEEE91898BF5E5BD CRC64;
     GRCCHPACGK NYSC