CA1A_CONVR
ID CA1A_CONVR Reviewed; 62 AA.
AC F5C0A0;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 25-MAY-2022, entry version 35.
DE RecName: Full=Alpha-conotoxin ViIA {ECO:0000303|PubMed:26511093};
DE AltName: Full=ViIA-II {ECO:0000303|PubMed:26511093};
DE Flags: Precursor;
OS Conus virgo (Virgin cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Virgiconus.
OX NCBI_TaxID=89427;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 46-61, MUTAGENESIS OF ARG-46;
RP ASP-47; HIS-56 AND CYS-61, AND DISULFIDE BOND.
RC TISSUE=Venom duct;
RX PubMed=26511093; DOI=10.1093/abbs/gmv105;
RA Li L., Liu N., Ding R., Wang S., Liu Z., Li H., Zheng X., Dai Q.;
RT "A novel 4/6-type alpha-conotoxin ViIA selectively inhibits nAchR
RT alpha3beta2 subtype.";
RL Acta Biochim. Biophys. Sin. 47:1023-1028(2015).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin selectively inhibits nicotinic acetylcholine receptor
CC (nAChR) alpha-3-beta-2 subtype (IC(50)=845.5 nM).
CC {ECO:0000269|PubMed:26511093}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:26511093}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:26511093}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/6 pattern.
CC {ECO:0000305|PubMed:26511093}.
CC -!- PTM: The toxin is inactive on the alpha-3-beta-2 nAChR when the
CC disulfide bond connectivity is C1-C4 and C2-C3 (ViIA-I) (IC(50)>10000
CC nM). {ECO:0000269|PubMed:26511093}.
CC -!- MISCELLANEOUS: This toxin does not inhibit alpha-2-beta-2, alpha-2-
CC beta-4, alpha-3-beta-4, alpha-4-beta-2, alpha-4-beta-4, alpha-7 and
CC alpha-9-alpha-10 (PubMed:26511093). In addition, it does not target
CC dorsal root ganglion sodium (Nav), potassium (Kv) and calcium (Cav) ion
CC channels (PubMed:26511093). {ECO:0000269|PubMed:26511093}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily.
CC {ECO:0000305|PubMed:26511093}.
CC -!- CAUTION: Authors of PubMed:26511093 indicate an amidation at Cys-61.
CC This amidation is improbable since no Gly follows the mature peptide
CC region. This PTM is therefore not indicated here and we assume that
CC electrophysiological results are obtained with an unamidated synthetic
CC peptide. {ECO:0000305|PubMed:26511093}.
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DR EMBL; JF436964; ADZ99320.1; -; mRNA.
DR AlphaFoldDB; F5C0A0; -.
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: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; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..45
FT /evidence="ECO:0000305"
FT /id="PRO_0000439627"
FT PEPTIDE 46..61
FT /note="Alpha-conotoxin ViIA"
FT /evidence="ECO:0000305|PubMed:26511093"
FT /id="PRO_5003322255"
FT DISULFID 48..54
FT /evidence="ECO:0000305|PubMed:26511093"
FT DISULFID 49..61
FT /evidence="ECO:0000305|PubMed:26511093"
FT MUTAGEN 46
FT /note="R->A: 1.6-fold more potent in inhibition of rat
FT alpha-3-beta-2 nAChR."
FT /evidence="ECO:0000269|PubMed:26511093"
FT MUTAGEN 47
FT /note="D->A: No change in inhibition of rat alpha-3-beta-2
FT nAChR."
FT /evidence="ECO:0000269|PubMed:26511093"
FT MUTAGEN 56
FT /note="H->A: Complete loss of effect on rat alpha-3-beta-2
FT nAChR."
FT /evidence="ECO:0000269|PubMed:26511093"
FT MUTAGEN 61
FT /note="C->CL: 13.6-fold more potent in inhibition of rat
FT alpha-3-beta-2 nAChR."
FT /evidence="ECO:0000269|PubMed:26511093"
SQ SEQUENCE 62 AA; 6810 MW; AE9764FFD3813190 CRC64;
MGMRMMFVVF LLVVFASSVT LDRASYGRYA SPVDRASALI AQAILRDCCS NPPCAHNNPD
CR