ID   CS8A_CONGE              Reviewed;          88 AA.
AC   P58924; D6C4G8;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2013, sequence version 2.
DT   25-MAY-2022, entry version 67.
DE   RecName: Full=Sigma-conotoxin GVIIIA {ECO:0000303|PubMed:9677203};
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 [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   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 47-87, HYDROXYLATION AT
RP   PRO-55, BROMINATION AT TRP-80, AMIDATION AT SER-87, SYNTHESIS OF 73-88,
RP   FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=9677203; DOI=10.1126/science.281.5376.575;
RA   England L.J., Imperial J.S., Jacobsen R.B., Craig A.G., Gulyas J.,
RA   Akhtar M., Rivier J.E., Julius D., Olivera B.M.;
RT   "Inactivation of a serotonin-gated ion channel by a polypeptide toxin from
RT   marine snails.";
RL   Science 281:575-578(1998).
RN   [3]
RP   ERRATUM OF PUBMED:9677203.
RA   England L.J., Imperial J.S., Jacobsen R.B., Craig A.G., Gulyas J.,
RA   Akhtar M., Rivier J.E., Julius D., Olivera B.M.;
RL   Science 282:417-417(1998).
RN   [4]
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: Sigma-conotoxins bind and inhibit serotonin-gated ion
CC       channels. This peptide selectively and reversibly inhibits 5-
CC       hydroxytryptamine 3 receptor (HTR3A) through competitive antagonism
CC       (IC(50)=53-86.8 nM). {ECO:0000269|PubMed:9677203, ECO:0000269|Ref.3}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9677203}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:9677203}.
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:9677203}.
CC   -!- MASS SPECTROMETRY: Mass=4187.6; Method=Electrospray; Note=Monoisotopic
CC       mass.; Evidence={ECO:0000269|PubMed:9677203};
CC   -!- SIMILARITY: Belongs to the conotoxin S superfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; FJ959110; ADB93080.1; -; Genomic_DNA.
DR   PIR; A59149; A59149.
DR   AlphaFoldDB; P58924; -.
DR   TCDB; 8.B.34.1.1; the sigma-conotoxin (sigma-conotoxin) family.
DR   ConoServer; 1724; GVIIIA precursor.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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   Amidation; Bromination; Direct protein sequencing; Disulfide bond;
KW   Hydroxylation; Ion channel impairing toxin; Neurotoxin; Secreted; Signal;
KW   Toxin.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..46
FT                   /evidence="ECO:0000269|PubMed:9677203"
FT                   /id="PRO_0000420714"
FT   PEPTIDE         47..87
FT                   /note="Sigma-conotoxin GVIIIA"
FT                   /evidence="ECO:0000269|PubMed:9677203"
FT                   /id="PRO_0000035015"
FT   MOD_RES         55
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:9677203"
FT   MOD_RES         80
FT                   /note="6'-bromotryptophan"
FT                   /evidence="ECO:0000269|PubMed:9677203"
FT   MOD_RES         87
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000269|PubMed:9677203"
SQ   SEQUENCE   88 AA;  9430 MW;  C847A5A9B9AD54CB CRC64;
     MMSKMGAMFV LLLLFTLASS LQEGDVQARK TRLKSDFYRA LARDDRGCTR TCGGPKCTGT
     CTCTNSSKCG CRYNVHPSGW GCGCACSG