NA123_ANEVI
ID NA123_ANEVI Reviewed; 80 AA.
AC P0DL51; 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 3 {ECO:0000303|PubMed:22683676};
DE Short=Delta-AITX-Avd1c 3 {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 Av2-3 {ECO:0000312|EMBL:ABW97328.1};
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; EU124449; ABW97328.1; -; Genomic_DNA.
DR AlphaFoldDB; P0DL51; -.
DR SMR; P0DL51; -.
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_0000433681"
FT CHAIN 34..80
FT /note="Delta-actitoxin-Avd1c 3"
FT /id="PRO_0000433795"
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
