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NA122_ANEVI
ID   NA122_ANEVI             Reviewed;          80 AA.
AC   P0DL50; B1NWR0;
DT   16-SEP-2015, integrated into UniProtKB/Swiss-Prot.
DT   16-SEP-2015, sequence version 1.
DT   25-MAY-2022, entry version 17.
DE   RecName: Full=Delta-actitoxin-Avd1c 2 {ECO:0000303|PubMed:22683676};
DE            Short=Delta-AITX-Avd1c 2 {ECO:0000303|PubMed:22683676};
DE   AltName: Full=Anemonia viridis toxin 2;
DE            Short=Av2 {ECO:0000303|PubMed:16846229};
DE            Short=Avt 2 {ECO:0000303|PubMed:22683676};
DE   AltName: Full=Toxin Av2-2 {ECO:0000312|EMBL:ABW97327.1};
DE   Flags: Precursor;
OS   Anemonia viridis (Snakelocks anemone).
OC   Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC   Actiniidae; Anemonia.
OX   NCBI_TaxID=51769;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=18222944; DOI=10.1093/molbev/msn021;
RA   Moran Y., Weinberger H., Sullivan J.C., Reitzel A.M., Finnerty J.R.,
RA   Gurevitz M.;
RT   "Concerted evolution of sea anemone neurotoxin genes is revealed through
RT   analysis of the Nematostella vectensis genome.";
RL   Mol. Biol. Evol. 25:737-747(2008).
RN   [2]
RP   MUTAGENESIS OF VAL-35; LEU-38; ASP-42; ASN-49; LEU-51 AND ILE-74, AND TOXIC
RP   DOSE.
RX   PubMed=16846229; DOI=10.1021/bi060386b;
RA   Moran Y., Cohen L., Kahn R., Karbat I., Gordon D., Gurevitz M.;
RT   "Expression and mutagenesis of the sea anemone toxin Av2 reveals key amino
RT   acid residues important for activity on voltage-gated sodium channels.";
RL   Biochemistry 45:8864-8873(2006).
RN   [3]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP   LEU-38.
RX   PubMed=22048953; DOI=10.1098/rspb.2011.1731;
RA   Moran Y., Genikhovich G., Gordon D., Wienkoop S., Zenkert C., Ozbek S.,
RA   Technau U., Gurevitz M.;
RT   "Neurotoxin localization to ectodermal gland cells uncovers an alternative
RT   mechanism of venom delivery in sea anemones.";
RL   Proc. R. Soc. B 279:1351-1358(2012).
RN   [4]
RP   NOMENCLATURE.
RX   PubMed=22683676; DOI=10.1016/j.toxicon.2012.05.020;
RA   Oliveira J.S., Fuentes-Silva D., King G.F.;
RT   "Development of a rational nomenclature for naming peptide and protein
RT   toxins from sea anemones.";
RL   Toxicon 60:539-550(2012).
CC   -!- FUNCTION: Binds specifically to voltage-gated sodium channels (Nav)
CC       (site 3), thereby delaying their inactivation during signal
CC       transduction (By similarity). Has a strong effect on crustaceans and
CC       insects and a weaker effect on mammals (By similarity). It strongly
CC       inhibits D.melanogaster sodium channel (DmNav1) (By similarity). It
CC       strongly affects the heart sodium channels (Nav1.5/SCN5A) and weakly
CC       inhibits the brain sodium channel Nav1.2/SCN2A (By similarity). In
CC       vivo, when released into the medium, this recombinant toxin induces
CC       impaired swimming, paralysis and death of the crustacean A.nauplii
CC       within several hours (PubMed:22048953). Its effect on zebrafish
CC       (D.rerio) larvae is much faster, since it induces paralysis or strong
CC       convulsion and impaired swimming, within 10 minutes (PubMed:22048953).
CC       {ECO:0000250|UniProtKB:P01528, ECO:0000269|PubMed:22048953}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:22048953}.
CC       Nematocyst {ECO:0000305|PubMed:22048953}. Note=In nematocyst, is
CC       associated with the tubule prior to discharge.
CC       {ECO:0000305|PubMed:22048953}.
CC   -!- TISSUE SPECIFICITY: Expressed in gland cells and nematocytes.
CC       {ECO:0000305|PubMed:22048953}.
CC   -!- TOXIC DOSE: Dose that immobilizes and contracts insects (ED(50)) is 3.7
CC       pmol/g body weight when intersegmentally injected into S.falculata.
CC       {ECO:0000269|PubMed:16846229}.
CC   -!- MISCELLANEOUS: This protein is encoded by at least 3 different genes.
CC       At least 3 other genes code for a similar Av2 with an Ile (instead a
CC       Val) at position 35. {ECO:0000269|PubMed:18222944}.
CC   -!- SIMILARITY: Belongs to the sea anemone sodium channel inhibitory toxin
CC       family. Type I subfamily. {ECO:0000305}.
CC   -!- CAUTION: Opinions are divided on whether Anemonia viridis (Forsskal,
CC       1775) and Anemonia sulcata (Pennant, 1777) are separate species.
CC       {ECO:0000305}.
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DR   EMBL; EU124448; ABW97327.1; -; Genomic_DNA.
DR   AlphaFoldDB; P0DL50; -.
DR   SMR; P0DL50; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.20.20.10; -; 1.
DR   InterPro; IPR023355; Myo_ane_neurotoxin_sf.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Disulfide bond;
KW   Ion channel impairing toxin; Nematocyst; Neurotoxin; Secreted; Signal;
KW   Toxin; Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..31
FT                   /evidence="ECO:0000250|UniProtKB:P01528"
FT                   /id="PRO_0000433680"
FT   CHAIN           34..80
FT                   /note="Delta-actitoxin-Avd1c 2"
FT                   /id="PRO_5000319683"
FT   DISULFID        37..77
FT                   /evidence="ECO:0000250|UniProtKB:P01528"
FT   DISULFID        39..67
FT                   /evidence="ECO:0000250|UniProtKB:P01528"
FT   DISULFID        60..78
FT                   /evidence="ECO:0000250|UniProtKB:P01528"
FT   MUTAGEN         35
FT                   /note="V->A: 9.8-fold decrease in binding affinity to
FT                   cockroach sodium channels and correlated loss of toxicity
FT                   to blowfly larvae."
FT                   /evidence="ECO:0000269|PubMed:16846229"
FT   MUTAGEN         38
FT                   /note="L->A: 27-fold decrease in binding affinity to
FT                   cockroach sodium channels and correlated loss of toxicity
FT                   to blowfly larvae. In vivo, slightly affects fish larvae
FT                   after several hours."
FT                   /evidence="ECO:0000269|PubMed:16846229,
FT                   ECO:0000269|PubMed:22048953"
FT   MUTAGEN         42
FT                   /note="D->A: 317-fold decrease in binding affinity to
FT                   cockroach sodium channels and correlated loss of toxicity
FT                   to blowfly larvae."
FT                   /evidence="ECO:0000269|PubMed:16846229"
FT   MUTAGEN         49
FT                   /note="N->A: 11-fold decrease in binding affinity to
FT                   cockroach sodium channels and correlated loss of toxicity
FT                   to blowfly larvae."
FT                   /evidence="ECO:0000269|PubMed:16846229"
FT   MUTAGEN         51
FT                   /note="L->A: 209-fold decrease in binding affinity to
FT                   cockroach sodium channels and correlated loss of toxicity
FT                   to blowfly larvae."
FT                   /evidence="ECO:0000269|PubMed:16846229"
FT   MUTAGEN         74
FT                   /note="I->A: 16-fold decrease in binding affinity to
FT                   cockroach sodium channels and correlated loss of toxicity
FT                   to blowfly larvae."
FT                   /evidence="ECO:0000269|PubMed:16846229"
SQ   SEQUENCE   80 AA;  8663 MW;  EEF3F54AABC65B3E CRC64;
     MMNRLLVFLM LGAAFMLVVS AIDQDANEDI NKRGVPCLCD SDGPSVRGNT LSGIIWLAGC
     PSGWHNCKKH GPTIGWCCKQ
 
 
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