ID   O1VA_CONGR              Reviewed;          74 AA.
AC   A0A2I4QAG8;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2018, sequence version 1.
DT   25-MAY-2022, entry version 14.
DE   RecName: Full=O-conotoxin GeXXXIA {ECO:0000305};
DE   AltName: Full=O-conotoxin GeXXVIIA {ECO:0000303|PubMed:28598389};
DE            Short=O-GeXXVIIA {ECO:0000303|PubMed:28598389};
DE   Flags: Precursor;
OS   Conus generalis (General cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Strategoconus.
OX   NCBI_TaxID=101304;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 34-52, FUNCTION,
RP   SUBCELLULAR LOCATION, SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=28598389; DOI=10.3390/md15060170;
RA   Jiang S., Tae H.S., Xu S., Shao X., Adams D.J., Wang C.;
RT   "Identification of a novel O-conotoxin reveals an unusual and potent
RT   inhibitor of the human alpha9alpha10 nicotinic acetylcholine receptor.";
RL   Mar. Drugs 15:1-13(2017).
CC   -!- FUNCTION: The activity of this natural homodimer has not been tested
CC       due to low abundance (PubMed:28598389). The synthetic linear peptide
CC       has been refolded, giving 4 different monomeric isomers (m1 to m4) with
CC       2 disulfide bonds each (PubMed:28598389). All isomers potently inhibit
CC       rat alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE and human
CC       alpha-9-alpha-10/CHRNA9-CHRNA10 nicotinic acetylcholine receptors
CC       (nAChR) (PubMed:28598389). In addition, they show a modest inhibition
CC       at human alpha-3-beta-2/CHRNA3-CHRNB2, alpha-3-beta-4/CHRNA3-CHRNB4,
CC       alpha-7/CHRNA7, and alpha-4-beta-4/CHRNA4-CHRNB4 (PubMed:28598389). The
CC       synthetic monomer peptide without disulfide bonds shows a potent
CC       activity on alpha-9-alpha-10/CHRNA9 AND CHRNA10 (IC(50)=16.2 nM)
CC       (PubMed:28598389). This linear peptide does not act as a competitive
CC       antagonist, or as a channel pore blocker of nAChR (PubMed:28598389).
CC       {ECO:0000269|PubMed:28598389}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:28598389}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28598389}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:28598389}.
CC   -!- DOMAIN: The cysteine framework is C-C-C-C-C. {ECO:0000305}.
CC   -!- PTM: May contain 2 intrachain disulfide bonds and probably one
CC       interchain disulfide bond forming the homodimer.
CC       {ECO:0000269|PubMed:28598389}.
CC   -!- PTM: The disulfide pairing is not important for activity towards the
CC       different nAChR subtypes, since this peptide without disulfide bond or
CC       with different disulfide bonds shows the same activity.
CC       {ECO:0000269|PubMed:28598389}.
CC   -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
CC   -!- CAUTION: Authors numbered this protein framework XXVII. Since this
CC       number is already attributed to another Cys arrangment (C-C-C-CCC-C-C),
CC       it is not indicated here to define the cysteine framework of this
CC       toxin. {ECO:0000305, ECO:0000305|PubMed:28598389}.
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DR   EMBL; KY523472; ARN17767.1; -; mRNA.
DR   AlphaFoldDB; A0A2I4QAG8; -.
DR   SMR; A0A2I4QAG8; -.
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:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR004214; Conotoxin.
DR   Pfam; PF02950; Conotoxin; 1.
PE   1: Evidence at protein level;
KW   Acetylcholine receptor inhibiting toxin; Direct protein sequencing;
KW   Disulfide bond; Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal;
KW   Toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..33
FT                   /evidence="ECO:0000305|PubMed:28598389"
FT                   /id="PRO_0000451081"
FT   CHAIN           34..74
FT                   /note="O-conotoxin GeXXXIA"
FT                   /evidence="ECO:0000269|PubMed:28598389"
FT                   /id="PRO_5014447851"
FT   CONFLICT        45
FT                   /note="L -> P (in Ref. 1; AA sequence)"
SQ   SEQUENCE   74 AA;  8540 MW;  C7785A2712B11A85 CRC64;
     MKLTCVLIIT VLFLTACQLT TAVTYSRGEH KHRALMSTGT NYRLLKTCRG SGRYCRSPYD
     CRRRYCRRIS DACV