CSA8A_CONGE
ID CSA8A_CONGE Reviewed; 88 AA.
AC X5IWT5;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 11-JUN-2014, sequence version 1.
DT 25-MAY-2022, entry version 14.
DE RecName: Full=Alpha-conotoxin GVIIIB {ECO:0000305};
DE AltName: Full=AlphaS-conotoxin GVIIIB {ECO:0000303|PubMed:26074268};
DE Flags: Precursor;
OS Conus geographus (Geography cone) (Nubecula geographus).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium.
OX NCBI_TaxID=6491;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=24662800; DOI=10.1038/ncomms4521;
RA Dutertre S., Jin A.-H., Vetter I., Hamilton B., Sunagar K., Lavergne V.,
RA Dutertre V., Fry B.G., Antunes A., Venter D.J., Alewood P.F., Lewis R.J.;
RT "Evolution of separate predation- and defence-evoked venoms in carnivorous
RT cone snails.";
RL Nat. Commun. 5:3521-3521(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 44-58, FUNCTION,
RP SUBCELLULAR LOCATION, PROBABLE AMIDATION AT THR-87, AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom duct;
RX PubMed=26074268; DOI=10.1016/j.bcp.2015.06.007;
RA Christensen S.B., Bandyopadhyay P.K., Olivera B.M., McIntosh J.M.;
RT "alphaS-conotoxin GVIIIB potently and selectively blocks alpha9alpha10
RT nicotinic acetylcholine receptors.";
RL Biochem. Pharmacol. 96:349-356(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 shows high activity on alpha-9-alpha-10 (CHRNA9-CHRNA10)
CC (IC(50)=9.79 nM) (PubMed:26074268). It also shows weak activity on
CC alpha-3-beta-2 (CHRNA3-CHRNB2) (IC(50)~1 uM), alpha-6/alpha-3-beta-2-
CC beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC(50)~1 uM) (PubMed:26074268).
CC The toxin binds to the same or overlapping binding sites than conotoxin
CC RgIA (AC P0C1D0) (PubMed:26074268). {ECO:0000269|PubMed:26074268}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26074268}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:26074268}.
CC -!- DOMAIN: The cysteine framework is VIII (C-C-C-C-C-C-C-C-C-C).
CC {ECO:0000305}.
CC -!- PTM: Contains 5 disulfide bonds. {ECO:0000269|PubMed:26074268}.
CC -!- PTM: The predominant peptide contains 2 hydroxyprolines, while 2 minor
CC peptides contains 1 and 3 hydroxyprolines.
CC {ECO:0000269|PubMed:26074268}.
CC -!- MASS SPECTROMETRY: Mass=4435.6; Method=MALDI; Note=Monoisotopic mass,
CC predominant peptide with 2 hydroxyprolines and 5 disulfide bonds.;
CC Evidence={ECO:0000269|PubMed:26074268};
CC -!- MASS SPECTROMETRY: Mass=4419.6; Method=MALDI; Note=Monoisotopic mass,
CC minor peptide with 1 hydroxyproline and 5 disulfide bonds.;
CC Evidence={ECO:0000269|PubMed:26074268};
CC -!- MASS SPECTROMETRY: Mass=4451.6; Method=MALDI; Note=Monoisotopic mass,
CC minor peptide with 3 hydroxyprolines and 5 disulfide bonds.;
CC Evidence={ECO:0000269|PubMed:26074268};
CC -!- MISCELLANEOUS: Shows no or weak activities on 5-hydroxytryptamine
CC receptor 3A (HTR3A), and alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-
CC CHRND-CHRNE), alpha-3 beta-4 (CHRNA3-CHRNB4), alpha-4 beta-2 (CHRNA3-
CC CHRNB2), and alpha-7/CHRNA7 nAChR. {ECO:0000269|PubMed:26074268}.
CC -!- SIMILARITY: Belongs to the conotoxin S superfamily. {ECO:0000305}.
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DR EMBL; AB910871; BAO65639.1; -; mRNA.
DR AlphaFoldDB; X5IWT5; -.
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.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond; Hydroxylation;
KW Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..43
FT /evidence="ECO:0000305|PubMed:26074268"
FT /id="PRO_0000444150"
FT PEPTIDE 44..87
FT /note="Alpha-conotoxin GVIIIB"
FT /evidence="ECO:0000305|PubMed:26074268"
FT /id="PRO_5004956869"
FT MOD_RES 87
FT /note="Threonine amide"
FT /evidence="ECO:0000305|PubMed:26074268"
SQ SEQUENCE 88 AA; 9377 MW; D336E578D99D227B CRC64;
MMSKMGAMFV LLLLFTLASS QQEGDVQARK TRPKSDFYRA LPRSGSTCTC FTSTNCQGSC
ECLSPPGCYC SNNGIRQPGC SCTCPGTG
