NA12_ANESU
ID NA12_ANESU Reviewed; 47 AA.
AC P01528;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Delta-actitoxin-Avd1c {ECO:0000303|PubMed:22683676};
DE Short=Delta-AITX-Avd1c {ECO:0000303|PubMed:22683676};
DE AltName: Full=ATX-II {ECO:0000303|PubMed:8660409};
DE Short=ATX II {ECO:0000303|PubMed:2409523};
DE AltName: Full=Anemonia sulcata toxin 2;
DE Short=As2;
DE AltName: Full=Neurotoxin 2;
DE AltName: Full=Toxin II {ECO:0000303|PubMed:30689, ECO:0000303|PubMed:9283};
OS Anemonia sulcata (Mediterranean snakelocks sea anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Anemonia.
OX NCBI_TaxID=6108;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Nematoblast;
RX PubMed=9283; DOI=10.1111/j.1432-1033.1976.tb10778.x;
RA Wunderer G., Fritz H., Wachter E., Machleidt W.;
RT "Amino-acid sequence of a coelenterate toxin: toxin II from Anemonia
RT sulcata.";
RL Eur. J. Biochem. 68:193-198(1976).
RN [2]
RP DISULFIDE BONDS.
RC TISSUE=Nematoblast;
RX PubMed=30689;
RA Wunderer G.;
RT "The disulfide bridges of toxin II from Anemonia sulcata.";
RL Hoppe-Seyler's Z. Physiol. Chem. 359:1193-1201(1978).
RN [3]
RP FUNCTION.
RX PubMed=2409523; DOI=10.1007/bf00585406;
RA Hartung K., Rathmayer W.;
RT "Anemonia sulcata toxins modify activation and inactivation of Na+ currents
RT in a crayfish neurone.";
RL Pflugers Arch. 404:119-125(1985).
RN [4]
RP FUNCTION.
RX PubMed=8660409; DOI=10.1007/s002329900083;
RA Chahine M., Plante E., Kallen R.G.;
RT "Sea anemone toxin (ATX II) modulation of heart and skeletal muscle sodium
RT channel alpha-subunits expressed in tsA201 cells.";
RL J. Membr. Biol. 152:39-48(1996).
RN [5]
RP FUNCTION.
RX PubMed=9236205; DOI=10.1085/jgp.110.2.119;
RA Warmke J.W., Reenan R.A., Wang P., Qian S., Arena J.P., Wang J.,
RA Wunderler D., Liu K., Kaczorowski G.J., Van der Ploeg L.H.T., Ganetzky B.,
RA Cohen C.J.;
RT "Functional expression of Drosophila para sodium channels. Modulation by
RT the membrane protein TipE and toxin pharmacology.";
RL J. Gen. Physiol. 110:119-133(1997).
RN [6]
RP FUNCTION.
RX PubMed=15169781; DOI=10.1074/jbc.m404344200;
RA Oliveira J.S., Redaelli E., Zaharenko A.J., Cassulini R.R., Konno K.,
RA Pimenta D.C., Freitas J.C., Clare J.J., Wanke E.;
RT "Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels:
RT unexpected contributions from differences in the IV/S3-S4 outer loop.";
RL J. Biol. Chem. 279:33323-33335(2004).
RN [7]
RP ERRATUM OF PUBMED:15169781.
RA Oliveira J.S., Redaelli E., Zaharenko A.J., Cassulini R.R., Konno K.,
RA Pimenta D.C., Freitas J.C., Clare J.J., Wanke E.;
RL J. Biol. Chem. 279:44229-44230(2004).
RN [8]
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. Has a strong effect on
CC crustaceans and insects (DmNav1) and a weaker effect on mammals. This
CC toxin is highly potent at mammalian Nav1.1/SCN1A (EC(50)=6.01 nM) and
CC Nav1.2/SCN2A (EC(50)=7.88 nM) (PubMed:15169781). It has also great
CC activity on Nav1.5/SCN5A (EC(50)=49.05 nM), Nav1.4/SCN4A (EC(50)=109.49
CC nM) and Nav1.6/SCN8A (EC(50)=about 180 nM) and is less potent on
CC Nav1.3/SCN3A (EC(50)=759.22 nM) (when measured as the increase in the
CC slow component) (PubMed:15169781). {ECO:0000269|PubMed:15169781,
CC ECO:0000269|PubMed:8660409, ECO:0000269|PubMed:9236205}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Nematocyst {ECO:0000305}.
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 PIR; A91240; TZAZ.
DR AlphaFoldDB; P01528; -.
DR SMR; P01528; -.
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 GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR Gene3D; 2.20.20.10; -; 1.
DR InterPro; IPR000693; Anenome_toxin.
DR InterPro; IPR023355; Myo_ane_neurotoxin_sf.
DR PIRSF; PIRSF001905; Anenome_toxin; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Nematocyst; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..47
FT /note="Delta-actitoxin-Avd1c"
FT /evidence="ECO:0000269|PubMed:9283"
FT /id="PRO_0000221513"
FT DISULFID 4..44
FT /evidence="ECO:0000269|PubMed:30689"
FT DISULFID 6..34
FT /evidence="ECO:0000269|PubMed:30689"
FT DISULFID 27..45
FT /evidence="ECO:0000269|PubMed:30689"
FT VARIANT 2
FT /note="V -> I (in 50% of the molecules)"
SQ SEQUENCE 47 AA; 4941 MW; BA0FAF370FA1D9CB CRC64;
GVPCLCDSDG PSVRGNTLSG IIWLAGCPSG WHNCKKHGPT IGWCCKQ
