CA12_CONPL
ID CA12_CONPL Reviewed; 41 AA.
AC A1X8D8;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Alpha-conotoxin-like Pu1.2;
DE Flags: Precursor; Fragment;
OS Conus pulicarius (Flea-bitten cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus.
OX NCBI_TaxID=93154;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=17400270; DOI=10.1016/j.toxicon.2007.02.011;
RA Yuan D.-D., Han Y.-H., Wang C.-G., Chi C.-W.;
RT "From the identification of gene organization of alpha conotoxins to the
RT cloning of novel toxins.";
RL Toxicon 49:1135-1149(2007).
RN [2]
RP FUNCTION, SYNTHESIS OF 22-37, AMIDATION AT CYS-37, AND MUTAGENESIS OF
RP 22-GLY--PRO-29; CYS-24; CYS-25; CYS-30 AND 31-ILE--CYS-37.
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 (By
CC similarity). This toxin also inhibits high voltage-activated (HVA)
CC calcium channel currents in rat DRG neurons (27% inhibition at 1 uM
CC toxin) 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). Alpha4/6 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 (25-30% inhibition at 1 uM toxin) (PubMed:26948522).
CC {ECO:0000269|PubMed:26948522}.
CC -!- PTM: Mutants Pu1.2(9-16), [C3S; C9S]Pu1.2 and [C4S]Pu1.2(1-9) are all
CC C-terminally amidated. {ECO:0000269|PubMed:26948522}.
CC -!- MISCELLANEOUS: This toxin does not inhibit human alpha-7/CHRNA7 and
CC alpha-9-alpha-10/CHRNA9-CHRNA10 acetylcholine receptors (when tested at
CC 3 uM) (PubMed:26948522). {ECO:0000269|PubMed:26948522}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; DQ311078; ABD33870.1; -; Genomic_DNA.
DR AlphaFoldDB; A1X8D8; -.
DR TCDB; 8.B.32.1.6; the nicotinic acetylcholine receptor-targeting alpha-conotoxin (a-conotoxin) family.
DR ConoServer; 568; Pu1.2 precursor.
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 Pfam; PF07365; Toxin_8; 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 Toxin.
FT PROPEP <1..21
FT /evidence="ECO:0000305|PubMed:26948522"
FT /id="PRO_0000370682"
FT PEPTIDE 22..37
FT /note="Alpha-conotoxin-like Pu1.2"
FT /evidence="ECO:0000305|PubMed:26948522"
FT /id="PRO_0000370683"
FT PROPEP 38..41
FT /evidence="ECO:0000305|PubMed:26948522"
FT /id="PRO_0000445674"
FT MOD_RES 37
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:26948522"
FT DISULFID 24..30
FT /evidence="ECO:0000250|UniProtKB:K8DWB5"
FT DISULFID 25..37
FT /evidence="ECO:0000250|UniProtKB:K8DWB5"
FT MUTAGEN 22..29
FT /note="Missing: In Pu1.2(9-16); Complete loss of HVA
FT calcium currents inhibition in rat DRG neurons."
FT /evidence="ECO:0000269|PubMed:26948522"
FT MUTAGEN 24
FT /note="C->S: In [C3S; C9S]Pu1.2; Complete loss of HVA
FT calcium currents inhibition in rat DRG neurons."
FT /evidence="ECO:0000269|PubMed:26948522"
FT MUTAGEN 25
FT /note="C->S: In [C4S]Pu1.2(1-9); No loss of HVA calcium
FT currents inhibition in rat DRG neurons (this effect could
FT be blocked by the selective GABA(B) receptor antagonist
FT CGP55845). No inhibition of human alpha-7/CHRNA7 and alpha-
FT 9-alpha-10/CHRNA9-CHRNA10 AChR."
FT /evidence="ECO:0000269|PubMed:26948522"
FT MUTAGEN 30
FT /note="C->S: In [C3S; C9S]Pu1.2; Complete loss of HVA
FT calcium currents inhibition in rat DRG neurons."
FT /evidence="ECO:0000269|PubMed:26948522"
FT MUTAGEN 31..37
FT /note="Missing: In [C4S]Pu1.2(1-9); No loss of HVA calcium
FT currents inhibition in rat DRG neurons (this effect could
FT be blocked by the selective GABA(B) receptor antagonist
FT CGP55845). No inhibition of human alpha-7/CHRNA7 and alpha-
FT 9-alpha-10/CHRNA9-CHRNA10 AChR."
FT /evidence="ECO:0000269|PubMed:26948522"
FT NON_TER 1
SQ SEQUENCE 41 AA; 4273 MW; 3E57E5FCC767873C CRC64;
LDGRNAAADF ETSDLLAMTI RGGCCSYPPC IANNPLCGGK R
