ID   CM3A_CONVA              Reviewed;          73 AA.
AC   H2BK78;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2012, sequence version 1.
DT   03-AUG-2022, entry version 26.
DE   RecName: Full=Conotoxin Vr3a {ECO:0000303|PubMed:34234819};
DE   AltName: Full=Vr3-NPPP01 {ECO:0000312|EMBL:AEX60199.1};
DE   Flags: Precursor;
OS   Conus varius (Varius cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Strategoconus.
OX   NCBI_TaxID=89448;
RN   [1] {ECO:0000312|EMBL:AEX60199.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=24080356; DOI=10.1016/j.toxicon.2013.09.020;
RA   Zhou M., Wang L., Wu Y., Zhu X., Feng Y., Chen Z., Li Y., Sun D., Ren Z.,
RA   Xu A.;
RT   "Characterizing the evolution and functions of the M-superfamily
RT   conotoxins.";
RL   Toxicon 76:150-159(2013).
RN   [2]
RP   FUNCTION, AND SYNTHESIS OF 53-73.
RX   PubMed=34234819; DOI=10.1590/1678-9199-jvatitd-2020-0164;
RA   Yang M., Li Y., Liu L., Zhou M.;
RT   "A novel proline-rich M-superfamily conotoxin that can simultaneously
RT   affect sodium, potassium and calcium currents.";
RL   J. Venom. Anim. Toxins Incl. Trop. Dis. 27:e20200164-e20200164(2021).
CC   -!- FUNCTION: Conotoxin with small effects on sodium (Nav), potassium (Kv)
CC       and calcium (Cav) currents. At high concentration (10 uM), it has no
CC       effects on the peak sodium currents, but induces a ~10 mV shift in a
CC       polarizing direction in the current-voltage relationship. At the same
CC       concentration, it increases 19% of the peak potassium currents but does
CC       not induce a shift in the current-voltage relationship. At the same
CC       concentration, it inhibits 31% of the peak calcium currents but does
CC       not induce a shift in the current-voltage relationship. On rat DRG
CC       neurons, it inhibits calcium channel currents with an IC(50)=19.28 uM.
CC       Moreover, at 10 uM, it inhibits 15.32% of the human Cav1.2/CACNA1C
CC       currents and 12.86% of the human Cav2.2/CACNA1B currents.
CC       {ECO:0000269|PubMed:34234819}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:24080356}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:24080356}.
CC   -!- DOMAIN: The cysteine framework is III (CC-C-C-CC). Classified in the M-
CC       4 branch, since 4 residues stand between the fourth and the fifth
CC       cysteine residues. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the conotoxin M superfamily. {ECO:0000305}.
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DR   EMBL; JF510712; AEX60199.1; -; mRNA.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR004214; Conotoxin.
DR   Pfam; PF02950; Conotoxin; 1.
PE   3: Inferred from homology;
KW   Disulfide bond; Hydroxylation; Ion channel impairing toxin; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   PROPEP          25..52
FT                   /evidence="ECO:0000305|PubMed:34234819"
FT                   /id="PRO_0000455039"
FT   PEPTIDE         53..73
FT                   /note="Conotoxin Vr3a"
FT                   /evidence="ECO:0000305|PubMed:34234819"
FT                   /id="PRO_5003559842"
FT   MOD_RES         57
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   MOD_RES         58
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   MOD_RES         68
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        55..66
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        56..71
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
FT   DISULFID        61..72
FT                   /evidence="ECO:0000250|UniProtKB:P01523"
SQ   SEQUENCE   73 AA;  8005 MW;  CD65C922E3685269 CRC64;
     MLKMGVVLFT VLVLFPLATL HLDAEQPVER YAENKQDINP DQRSGFLTFA LRQGCCPPGV
     CQMAACNPPP CCP