ID   CA12_CONPE              Reviewed;          56 AA.
AC   P0DM23;
DT   07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT   07-NOV-2018, sequence version 1.
DT   25-MAY-2022, entry version 10.
DE   RecName: Full=Alpha-conotoxin Pn1.2 {ECO:0000303|PubMed:26948522};
DE   Flags: Precursor;
OS   Conus pennaceus (Feathered cone) (Conus episcopus).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Darioconus.
OX   NCBI_TaxID=37335;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RA   Watkins M., Olivera B.M., Hillyard D.R., Mcintosh M.J., Jones R.M.;
RT   "Alpha-conotoxin peptides.";
RL   Patent number JP2002534996, 22-OCT-2002.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Venom;
RA   Watkins M., Olivera B.M., Hillyard D.R., McIntosh J.M., Jones R.M.;
RT   "Alpha-conotoxin peptides.";
RL   Patent number US6797808, 28-SEP-2004.
RN   [3]
RP   FUNCTION, SYNTHESIS OF 40-55, AND AMIDATION AT CYS-55.
RX   PubMed=26948522; DOI=10.1002/anie.201600297;
RA   Carstens B.B., Berecki G., Daniel J.T., Lee H.S., Jackson K.A., Tae H.S.,
RA   Sadeghi M., Castro J., O'Donnell T., Deiteren A., Brierley S.M.,
RA   Craik D.J., Adams D.J., Clark R.J.;
RT   "Structure-activity studies of cysteine-rich alpha-conotoxins that inhibit
RT   high-voltage-activated calcium channels via GABA(B) receptor activation
RT   reveal a minimal functional motif.";
RL   Angew. Chem. Int. Ed. 55:4692-4696(2016).
CC   -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC       the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC       This toxin inhibits human alpha-7/CHRNA7 and alpha-9-alpha-
CC       10/CHRNA9/CHRNA10 AChR (complete inhibition at 3 uM of toxin). In
CC       addition, this toxin inhibits high voltage-activated (HVA) calcium
CC       channel currents in rat DRG neurons (22% inhibition at 1 uM toxin)
CC       probably by activating GABA(B) receptors (GABBR1 and/or GABBR2)
CC       (PubMed:26948522). {ECO:0000250|UniProtKB:P0CE73,
CC       ECO:0000269|PubMed:26948522}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.
CC   -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC       {ECO:0000305}.
CC   -!- PTM: Non-native isomers 'ribbon' (with disulfide connectivity C1-C4;
CC       C2-C3) and 'beads' (with disulfide connectivity C1-C2; C3-C4) also
CC       inhibit high voltage-activated (HVA) calcium channel currents in rat
CC       DRG neurons (20-30% inhibition at 1 uM toxin) (Ref.1).
CC       {ECO:0000269|Ref.1}.
CC   -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR   EMBL; BD261424; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR   EMBL; AR584831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; P0DM23; -.
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; IPR009958; Conotoxin_a-typ.
DR   InterPro; IPR018072; Conotoxin_a-typ_CS.
DR   Pfam; PF07365; Toxin_8; 1.
DR   PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   Acetylcholine receptor inhibiting toxin; Amidation; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   PROPEP          17..39
FT                   /evidence="ECO:0000305|PubMed:26948522"
FT                   /id="PRO_0000445677"
FT   PEPTIDE         40..55
FT                   /note="Alpha-conotoxin Pn1.2"
FT                   /evidence="ECO:0000305|PubMed:26948522"
FT                   /id="PRO_0000445678"
FT   REGION          43..45
FT                   /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT                   with nAChR"
FT                   /evidence="ECO:0000250|UniProtKB:P56636"
FT   MOD_RES         55
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000305|PubMed:26948522"
FT   DISULFID        41..47
FT                   /evidence="ECO:0000305|PubMed:26948522"
FT   DISULFID        42..55
FT                   /evidence="ECO:0000305|PubMed:26948522"
SQ   SEQUENCE   56 AA;  5886 MW;  42FBC0B4F89072DB CRC64;
     MFTVFLLVVL ATTVVSFTSD RASDGGNAAM SDLIALTIKG CCSHPPCFLN NPDYCG