CA1A_CONPU
ID CA1A_CONPU Reviewed; 40 AA.
AC P69658;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 1.
DT 25-MAY-2022, entry version 65.
DE RecName: Full=Alpha-conotoxin PIA {ECO:0000303|PubMed:13679412};
DE Flags: Precursor; Fragment;
OS Conus purpurascens (Purple cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Chelyconus.
OX NCBI_TaxID=41690;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SYNTHESIS OF 22-39, FUNCTION, AND
RP AMIDATION AT CYS-39.
RC TISSUE=Hepatopancreas, and Venom duct;
RX PubMed=13679412; DOI=10.1523/jneurosci.23-24-08445.2003;
RA Dowell C., Olivera B.M., Garrett J.E., Staheli S.T., Watkins M.,
RA Kuryatov A., Yoshikami D., Lindstrom J.M., McIntosh J.M.;
RT "Alpha-conotoxin PIA is selective for alpha6 subunit-containing nicotinic
RT acetylcholine receptors.";
RL J. Neurosci. 23:8445-8452(2003).
RN [2]
RP STRUCTURE BY NMR OF 22-39, AND DISULFIDE BONDS.
RX PubMed=16289101; DOI=10.1016/j.bbrc.2005.10.176;
RA Chi S.-W., Lee S.-H., Kim D.-H., Kim J.-S., Olivera B.M., McIntosh J.M.,
RA Han K.-H.;
RT "Solution structure of alpha-conotoxin PIA, a novel antagonist of alpha6
RT subunit containing nicotinic acetylcholine receptors.";
RL Biochem. Biophys. Res. Commun. 338:1990-1997(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom {ECO:0000303|PubMed:13679412};
RX PubMed=28917942; DOI=10.1016/j.neuropharm.2017.09.020;
RA Hoggard M.F., Rodriguez A.M., Cano H., Clark E., Tae H.S., Adams D.J.,
RA Godenschwege T.A., Mari F.;
RT "In vivo and in vitro testing of native alpha-conotoxins from the injected
RT venom of Conus purpurascens.";
RL Neuropharmacology 127:253-259(2017).
CC -!- FUNCTION: Alpha-conotoxins bind to the nicotinic acetylcholine
CC receptors (nAChR) and inhibit them (PubMed:13679412, PubMed:28917942).
CC This toxin blocks mammalian nAChRs (alpha-6 or -3/beta-2 or -3 > alpha-
CC 3/beta-2 > alpha-3/beta-4) when heterologously expressed in Xenopus
CC oocytes (PubMed:13679412, PubMed:28917942). Does not block the muscle
CC nor the major neuronal nAChR alpha-4/beta-2 (PubMed:13679412).
CC Discriminates between nAChRs containing alpha-6 and alpha-3 subunits,
CC being selective for alpha-6 (PubMed:13679412). Also reduces the
CC frequency of responses from the giant fiber (GF)-dorsal longitudinal
CC muscle pathway in the D.melanogaster GF circuit, but has no effect on
CC the GF-tergo trochanteral muscle pathway (PubMed:28917942).
CC {ECO:0000269|PubMed:13679412, ECO:0000269|PubMed:28917942}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28917942}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:13679412, ECO:0000305|PubMed:28917942}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=1980.94; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:28917942};
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR PDB; 1ZLC; NMR; -; A=22-39.
DR PDBsum; 1ZLC; -.
DR AlphaFoldDB; P69658; -.
DR SMR; P69658; -.
DR ConoServer; 410; PIA precursor.
DR EvolutionaryTrace; P69658; -.
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; IDA:UniProtKB.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IDA:UniProtKB.
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 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL <1..?
FT /evidence="ECO:0000255"
FT PROPEP ?..21
FT /evidence="ECO:0000305"
FT /id="PRO_0000034885"
FT PEPTIDE 22..39
FT /note="Alpha-conotoxin PIA"
FT /evidence="ECO:0000269|PubMed:28917942,
FT ECO:0000305|PubMed:13679412"
FT /id="PRO_0000034886"
FT REGION 27..29
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 39
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:13679412"
FT DISULFID 25..31
FT /evidence="ECO:0000269|PubMed:16289101"
FT DISULFID 26..39
FT /evidence="ECO:0000269|PubMed:16289101"
FT NON_TER 1
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1ZLC"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:1ZLC"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:1ZLC"
SQ SEQUENCE 40 AA; 4171 MW; CC004666DA296996 CRC64;
SDGRDAAAND KATDLIALTA RRDPCCSNPV CTVHNPQICG
