CA1A_CONAE
ID CA1A_CONAE Reviewed; 39 AA.
AC P0C8R2;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 25-MAY-2022, entry version 34.
DE RecName: Full=Alpha-conotoxin ArIA {ECO:0000303|PubMed:17497892};
DE Contains:
DE RecName: Full=Alpha-conotoxin ArIB {ECO:0000303|PubMed:17497892};
DE Flags: Precursor; Fragment;
OS Conus arenatus (Sand-dusted cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus.
OX NCBI_TaxID=89451;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 20-39, MUTAGENESIS OF
RP 25-ASN--ALA-27; VAL-30 AND VAL-35, AND HYDROXYLATION AT PRO-33.
RX PubMed=17497892; DOI=10.1021/bi7004202;
RA Whiteaker P., Christensen S., Yoshikami D., Dowell C., Watkins M.,
RA Gulyas J., Rivier J., Olivera B.M., McIntosh J.M.;
RT "Discovery, synthesis, and structure activity of a highly selective alpha7
RT nicotinic acetylcholine receptor antagonist.";
RL Biochemistry 46:6628-6638(2007).
RN [2]
RP MUTAGENESIS OF VAL-30 AND VAL-35.
RX PubMed=18664588; DOI=10.1124/jpet.108.142943;
RA Innocent N., Livingstone P.D., Hone A., Kimura A., Young T., Whiteaker P.,
RA McIntosh J.M., Wonnacott S.;
RT "Alpha-conotoxin Arenatus IB[V11L,V16D] is a potent and selective
RT antagonist at rat and human native alpha7 nicotinic acetylcholine
RT receptors.";
RL J. Pharmacol. Exp. Ther. 327:529-537(2008).
RN [3]
RP ERRATUM OF PUBMED:18664588.
RA Innocent N., Livingstone P.D., Hone A., Kimura A., Young T., Whiteaker P.,
RA McIntosh J.M., Wonnacott S.;
RT "Correction to 'alpha-conotoxin Arenatus IB[V11l,V16D] is a potent and
RT selective antagonist at rat and human native alpha7 nicotinic acetylcholine
RT receptors'.";
RL J. Pharmacol. Exp. Ther. 327:1001-1001(2008).
CC -!- FUNCTION: [Alpha-conotoxin ArIA]: Alpha-conotoxins act on postsynaptic
CC membranes, they bind to the nicotinic acetylcholine receptors (nAChR)
CC and thus inhibit them. This toxin acts as a competitive inhibitor and
CC is 3-fold more potent on alpha-7/CHRNA7 nAChRs (IC(50)=6 nM) than on
CC alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (IC(50)=18 nM).
CC {ECO:0000269|PubMed:17497892}.
CC -!- FUNCTION: [Alpha-conotoxin ArIB]: Acts as a competitive inhibitor and
CC is 33-fold more potent on alpha-7/CHRNA7 nAChRs (IC(50)=1.8 nM) than on
CC alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (IC(50)=60.1 nM).
CC {ECO:0000269|PubMed:17497892}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:17497892}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:17497892}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: The mutant ArIB[V30L,V35D] is a potent and selective
CC competitive antagonist of rat and human alpha-7/CHRNA7 nAChRs, making
CC it an attractive probe for this receptor subtype.
CC {ECO:0000269|PubMed:17497892, ECO:0000269|PubMed:18664588}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0C8R2; -.
DR ConoServer; 2838; ArIA precursor.
DR ConoServer; 3450; Sequence 299 from Patent EP1852440.
DR ConoServer; 351; Sequence 300 from patent US 6797808.
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; Disulfide bond; Hydroxylation;
KW Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW Toxin.
FT PROPEP <1..17
FT /evidence="ECO:0000250"
FT /id="PRO_0000363985"
FT PEPTIDE 18..36
FT /note="Alpha-conotoxin ArIA"
FT /evidence="ECO:0000305|PubMed:17497892"
FT /id="PRO_0000363986"
FT PEPTIDE 20..36
FT /note="Alpha-conotoxin ArIB"
FT /evidence="ECO:0000305|PubMed:17497892"
FT /id="PRO_0000363987"
FT REGION 24..26
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 33
FT /note="4-hydroxyproline; in ArIA"
FT /evidence="ECO:0000305|PubMed:17497892"
FT DISULFID 22..28
FT /evidence="ECO:0000305|PubMed:17497892"
FT DISULFID 23..36
FT /evidence="ECO:0000305|PubMed:17497892"
FT MUTAGEN 25..27
FT /note="NPA->RPP: 8.8-fold decrease in inhibition of alpha-
FT 7/CHRNA7 and 2.5 increase in inhibition of alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:17497892"
FT MUTAGEN 30
FT /note="V->L: 3.4-fold and 1.5-fold increase in inhibition
FT of alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNA2 nAChR
FT (ArIB[V30L]). 5.1-fold increase in inhibition of alpha-
FT 7/CHRNA7 and 1.2-fold decrease in inhibition of alpha-3-
FT beta-2/CHRNA3-CHRNB2 nAChR; when associated with A-35
FT (ArIB[V30L,V35A]). 1.7-fold increase in inhibition of
FT alpha-7/CHRNA7 and complete loss of inhibition of alpha-3-
FT beta-2/CHRNA3-CHRNB2 nAChR; when associated with D-35
FT (ArIB[V30L,V35D])."
FT /evidence="ECO:0000269|PubMed:17497892"
FT MUTAGEN 35
FT /note="V->A: 5.1-fold increase in inhibition of alpha-
FT 7/CHRNA7 and 1.2-fold decrease in inhibition of alpha-3-
FT beta-2/CHRNA3-CHRNB2 nAChR; when associated with L-30
FT (ArIB[V30L,V35A])."
FT /evidence="ECO:0000269|PubMed:17497892"
FT MUTAGEN 35
FT /note="V->D: 1.7-fold increase in inhibition of alpha-
FT 7/CHRNA7 and complete loss of inhibition of alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR; when associated with L-30
FT (ArIB[V30L,V35D])."
FT /evidence="ECO:0000269|PubMed:17497892"
FT NON_TER 1
SQ SEQUENCE 39 AA; 4437 MW; F16F910269E507B6 CRC64;
SDGRNVAAKA FHRIGRTIRD ECCSNPACRV NNPHVCRRR
