ID   CSA8A_CONRA             Reviewed;          93 AA.
AC   P0C1W3; D6C4H2;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   08-FEB-2011, sequence version 2.
DT   25-MAY-2022, entry version 40.
DE   RecName: Full=Alpha-conotoxin RVIIIA {ECO:0000305};
DE   AltName: Full=AlphaS-conotoxin RVIIIA {ECO:0000303|PubMed:15910004, ECO:0000303|PubMed:26074268};
DE   Flags: Precursor;
OS   Conus radiatus (Rayed cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Phasmoconus.
OX   NCBI_TaxID=61198;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=20363338; DOI=10.1016/j.ympev.2010.03.029;
RA   Biggs J.S., Watkins M., Puillandre N., Ownby J.P., Lopez-Vera E.,
RA   Christensen S., Moreno K.J., Bernaldez J., Licea-Navarro A., Corneli P.S.,
RA   Olivera B.M.;
RT   "Evolution of Conus peptide toxins: analysis of Conus californicus Reeve,
RT   1844.";
RL   Mol. Phylogenet. Evol. 56:1-12(2010).
RN   [2]
RP   PROTEIN SEQUENCE OF 47-93, PARTIAL NUCLEOTIDE SEQUENCE [MRNA],
RP   GAMMA-CARBOXYGLUTAMATION AT GLU-63 AND GLU-68, MASS SPECTROMETRY, FUNCTION,
RP   AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom, and Venom duct;
RX   PubMed=15910004; DOI=10.1021/bi047274+;
RA   Teichert R.W., Jimenez E.C., Olivera B.M.;
RT   "Alpha S-conotoxin RVIIIA: a structurally unique conotoxin that broadly
RT   targets nicotinic acetylcholine receptors.";
RL   Biochemistry 44:7897-7902(2005).
RN   [3]
RP   FUNCTION.
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 provokes a nearly complete and slowly reversible inhibition
CC       of both the human adult (alpha-1-beta-1-epsilon-delta (CHRNA1-CHRNB1-
CC       CHRND-CHRNE)) and human fetal (alpha-1-beta-1-gamma-delta (CHRNA1-
CC       CHRNB1-CHRNG-CHRND)) neuromuscular nAChRs (PubMed:15910004,
CC       PubMed:26074268). It also reversibly blocks the neuromuscular alpha-
CC       7/CHRNA7 nAChR, the alpha-3-beta-2 (CHRNA3-CHRNB2) nAChR, the chimeric
CC       alpha-6 or -3/beta-3 or -2 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR and with
CC       a low potency the alpha-4-beta-2 (CHRNA4-CHRNB2) nAChR
CC       (PubMed:15910004). In addition, the toxin also inhibits the alpha-9-
CC       alpha-10 (CHRNA9-CHRNA10) nAChR with a high potency (IC(50)=187 nM)
CC       (PubMed:26074268). {ECO:0000269|PubMed:15910004,
CC       ECO:0000269|PubMed:26074268}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15910004}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:15910004}.
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:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=5168.99; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:15910004};
CC   -!- SIMILARITY: Belongs to the conotoxin S superfamily. {ECO:0000305}.
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DR   EMBL; FJ959114; ADB93084.1; -; Genomic_DNA.
DR   AlphaFoldDB; P0C1W3; -.
DR   ConoServer; 1574; RVIIIA.
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; Direct protein sequencing;
KW   Disulfide bond; Gamma-carboxyglutamic acid; Ion channel impairing toxin;
KW   Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..46
FT                   /evidence="ECO:0000269|PubMed:15910004"
FT                   /id="PRO_0000404999"
FT   PEPTIDE         47..93
FT                   /note="Alpha-conotoxin RVIIIA"
FT                   /evidence="ECO:0000269|PubMed:15910004"
FT                   /id="PRO_0000249790"
FT   MOD_RES         63
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000269|PubMed:15910004"
FT   MOD_RES         68
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000269|PubMed:15910004"
SQ   SEQUENCE   93 AA;  10383 MW;  AFAE4E9E632D1952 CRC64;
     MMSKMGAMFV LLLLFTLASS QQEGDVQARK THPKREFQRI LLRSGRKCNF DKCKGTGVYN
     CGESCSCEGL HSCRCTYNIG SMKSGCACIC TYY