ID   CAI15_CONGE             Reviewed;          67 AA.
AC   X5I9Z2;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   11-JUN-2014, sequence version 1.
DT   03-AUG-2022, entry version 22.
DE   RecName: Full=Alpha-conotoxin G1.5 {ECO:0000303|PubMed:34062129};
DE   Flags: Precursor;
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] {ECO:0000312|EMBL:BAO65592.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=24662800; DOI=10.1038/ncomms4521;
RA   Dutertre S., Jin A.-H., Vetter I., Hamilton B., Sunagar K., Lavergne V.,
RA   Dutertre V., Fry B.G., Antunes A., Venter D.J., Alewood P.F., Lewis R.J.;
RT   "Evolution of separate predation- and defence-evoked venoms in carnivorous
RT   cone snails.";
RL   Nat. Commun. 5:3521-3521(2014).
RN   [2]
RP   SYNTHESIS OF 48-65 AS GLOBULAR AND RIBBON ISOMER, FUNCTION, AND PROBABLE
RP   AMIDATION AT GLN-65.
RX   PubMed=34062129; DOI=10.1016/j.bcp.2021.114638;
RA   Tae H.S., Gao B., Jin A.H., Alewood P.F., Adams D.J.;
RT   "Globular and ribbon isomers of Conus geographus alpha-conotoxins
RT   antagonize human nicotinic acetylcholine receptors.";
RL   Biochem. Pharmacol. 190:114638-114638(2021).
CC   -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC       the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC       Globular isomer (C1-C3; C2-C4) selectively inhibits neuronal (non-
CC       muscle) nAChR subtypes particularly human alpha-3-beta-2/CHRNA3-CHRNB2
CC       (IC(50)=35.7 nM) and alpha-9-alpha-10/CHRNA9-CHRNA10 nAChRs (IC(50)=569
CC       nM), while the ribbon isomer (C1-C4; C2-C3) shows weak inhibition on
CC       alpha-3-beta-2/CHRNA3-CHRNB2, but not on all other receptors tested.
CC       {ECO:0000269|PubMed:34062129}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:34062129}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:34062129}.
CC   -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC       {ECO:0000305}.
CC   -!- MISCELLANEOUS: Both the globular (with C1-C3; C2-C4 disulfide pattern)
CC       and ribbon (C1-C4; C2-C3) isomers shows no or very weak inhibitory
CC       activity on muscle-type alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-
CC       CHRND-CHRNE nAChRs, alpha-4-beta-2/CHRNA4-CHRNB2, alpha-3-beta-
CC       4/CHRNA3-CHRNB4 (IC(50)=1928 nM by globular isomer), and alpha-7/CHRNA7
CC       (IC(50)=1935 nM by globular isomer). {ECO:0000269|PubMed:34062129}.
CC   -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AB910824; BAO65592.1; -; mRNA.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR009958; Conotoxin_a-typ.
DR   Pfam; PF07365; Toxin_8; 1.
PE   1: Evidence at protein level;
KW   Acetylcholine receptor inhibiting toxin; Amidation;
KW   Cleavage on pair of basic residues; Disulfide bond; Neurotoxin;
KW   Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..47
FT                   /evidence="ECO:0000305|PubMed:34062129"
FT                   /id="PRO_0000454095"
FT   PEPTIDE         48..65
FT                   /note="Alpha-conotoxin G1.5"
FT                   /evidence="ECO:0000305|PubMed:34062129"
FT                   /id="PRO_5004957488"
FT   MOD_RES         65
FT                   /note="Glutamine amide"
FT                   /evidence="ECO:0000305|PubMed:34062129"
FT   DISULFID        49..55
FT                   /evidence="ECO:0000250|UniProtKB:Q86RB2"
FT   DISULFID        50..63
FT                   /evidence="ECO:0000250|UniProtKB:Q86RB2"
SQ   SEQUENCE   67 AA;  7306 MW;  AAA6D6545452EFAE CRC64;
     MGMRMMFTVF LLVALATTVV SFTSDRASDR RNAAVKAFDL ISSTVKKGCC SHPACSGNNP
     EYCRQGR