ID   CDKA_CONVX              Reviewed;          92 AA.
AC   P0C1W5; C4PWC1;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   02-MAR-2010, sequence version 2.
DT   25-MAY-2022, entry version 39.
DE   RecName: Full=Alpha-conotoxin VxXXA {ECO:0000303|PubMed:19275168};
DE   AltName: Full=Vx20.1 {ECO:0000312|EMBL:CAX51119.1};
DE   AltName: Full=VxXIIA {ECO:0000303|PubMed:16790424};
DE   Flags: Precursor;
OS   Conus vexillum (Flag cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Rhizoconus.
OX   NCBI_TaxID=89431;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=19275168; DOI=10.1021/bi9000326;
RA   Loughnan M.L., Nicke A., Lawrence N., Lewis R.J.;
RT   "Novel alpha D-conopeptides and their precursors identified by cDNA cloning
RT   define the D-conotoxin superfamily.";
RL   Biochemistry 48:3717-3729(2009).
RN   [2]
RP   PROTEIN SEQUENCE OF 46-92, HYDROXYLATION AT PRO-55; PRO-70 AND PRO-74, MASS
RP   SPECTROMETRY, SUBUNIT, STRUCTURE BY NMR, FUNCTION, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Venom;
RX   PubMed=16790424; DOI=10.1074/jbc.m603703200;
RA   Loughnan M., Nicke A., Jones A., Schroeder C.I., Nevin S.T., Adams D.J.,
RA   Alewood P.F., Lewis R.J.;
RT   "Identification of a novel class of nicotinic receptor antagonists: dimeric
RT   conotoxins VxXIIA, VxXIIB and VxXIIC from Conus vexillum.";
RL   J. Biol. Chem. 281:24745-24755(2006).
CC   -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC       the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC       This toxin specifically blocks mammalian neuronal nAChR of the alpha-
CC       7/CHRNA7, alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=370 nM) and alpha-4-
CC       beta-2/CHRNA4-CHRNB2 subtypes. VxXXB inhibits alpha-7/CHRNA7 and alpha-
CC       3-beta-2/CHRNA3-CHRNB2 nAChR subtypes with the highest efficiency,
CC       followed by VxXXA and VxXXC. VxXXB and VxXXC inhibit the alpha-4-beta-
CC       2/CHRNA4-CHRNB2 nAChR subtype more efficiently than VxXXA.
CC       {ECO:0000269|PubMed:16790424}.
CC   -!- SUBUNIT: Homodimer or pseudo-homodimer. Three dimers exist: homodimer
CC       of VxXXA, pseudo-homodimer of both VxXXA and [hydroxyPro-74]VxXXA and
CC       homodimer of [hydroxyPro-74]VxXXA. These three components exist in a
CC       1:2:1 ratio. {ECO:0000269|PubMed:16790424}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16790424}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:16790424}.
CC   -!- DOMAIN: The cysteine framework is XX (C-CC-C-CC-C-C-C-C).
CC       {ECO:0000305}.
CC   -!- PTM: Contains 5 disulfide bonds. {ECO:0000305}.
CC   -!- PTM: VxXXA stands for the form with the Pro-55 hydroxylated. A second
CC       major form has both Pro-55 and Pro-74 hydroxylated. The two major forms
CC       VxXXA and [hydroxyPro-74]VxXXA exist in a 1:1 ratio.
CC       {ECO:0000269|PubMed:16790424}.
CC   -!- PTM: Minor forms are [hydroxyPro-70,hydroxyPro-74]VxXXA and [Pro-
CC       55]VxXXA. {ECO:0000269|PubMed:16790424}.
CC   -!- MASS SPECTROMETRY: Mass=5134.6; Method=Electrospray; Note=With
CC       hydroxyPro-55.; Evidence={ECO:0000269|PubMed:16790424};
CC   -!- MASS SPECTROMETRY: Mass=5150.6; Method=Electrospray; Note=With
CC       hydroxyPro-55 and hydroxyPro-74.;
CC       Evidence={ECO:0000269|PubMed:16790424};
CC   -!- SIMILARITY: Belongs to the conotoxin D superfamily. {ECO:0000305}.
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DR   EMBL; FN178633; CAX51119.1; -; mRNA.
DR   AlphaFoldDB; P0C1W5; -.
DR   SMR; P0C1W5; -.
DR   ConoServer; 1686; VxXXA.
DR   ConoServer; 3630; VxXXA precursor.
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; Hydroxylation; Ion channel impairing toxin; Neurotoxin;
KW   Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   PROPEP          25..45
FT                   /evidence="ECO:0000269|PubMed:16790424"
FT                   /id="PRO_0000391782"
FT   CHAIN           46..92
FT                   /note="Alpha-conotoxin VxXXA"
FT                   /evidence="ECO:0000269|PubMed:16790424"
FT                   /id="PRO_0000249793"
FT   MOD_RES         55
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000269|PubMed:16790424"
FT   MOD_RES         70
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000269|PubMed:16790424"
FT   MOD_RES         74
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000269|PubMed:16790424"
SQ   SEQUENCE   92 AA;  10113 MW;  EF52B139C26F83E1 CRC64;
     MPKLEMMLLV LLIFPLSYFI AAGGQVVQVD RRGDGLAGYL QRGDRDVQDC QVSTPGSKWG
     RCCLNRVCGP MCCPASHCYC VYHRGRGHGC SC