NA23_HETCR
ID NA23_HETCR Reviewed; 48 AA.
AC P30832;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 25-MAY-2022, entry version 73.
DE RecName: Full=Delta-stichotoxin-Hcr1a {ECO:0000303|PubMed:22683676};
DE Short=Delta-SHTX-Hcr1a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Neurotoxin III {ECO:0000303|PubMed:2573358, ECO:0000303|Ref.1};
DE AltName: Full=RTX-III;
DE AltName: Full=Rm3;
DE Contains:
DE RecName: Full=Delta-stichotoxin-Hcr1f {ECO:0000305};
DE Short=Delta-SHTX-Hcr1f {ECO:0000305};
DE AltName: Full=RTX-VI {ECO:0000303|PubMed:33368037};
OS Heteractis crispa (Leathery sea anemone) (Radianthus macrodactylus).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Stichodactylidae; Heteractis.
OX NCBI_TaxID=175771;
RN [1]
RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RA Zykova T.A., Vinokurov L.M., Kozlovskaya E.P., Elyakov G.B.;
RT "Amino-acid sequence of neurotoxin III from the sea anemone Radianthus
RT macrodactylus.";
RL Bioorg. Khim. 11:302-310(1985).
RN [2]
RP PROTEIN SEQUENCE OF 1-12 AND 14-48, FUNCTION, SUBCELLULAR LOCATION, AND
RP AMIDATION AT LYS-48.
RX PubMed=33368037; DOI=10.1134/s1607672920060071;
RA Kalina R.S., Peigneur S., Gladkikh I.N., Dmitrenok P.S., Kim N.Y.,
RA Leychenko E.V., Monastyrnaya M.M., Tytgat J., Kozlovskaya E.P.;
RT "New sea anemone toxin RTX-VI selectively modulates voltage-gated sodium
RT channels.";
RL Dokl. Biochem. Biophys. 495:292-295(2020).
RN [3]
RP DISULFIDE BONDS.
RX PubMed=2573358;
RA Zykova T.A., Kozlovskaya E.P.;
RT "Disulfide bonds in neurotoxin-III from the sea anenome Radianthus
RT macrodactylus.";
RL Bioorg. Khim. 15:904-907(1989).
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: [Delta-stichotoxin-Hcr1a]: Binds to site 3 of voltage-gated
CC sodium channels and inhibits the inactivation process. Specifically
CC inhibits mammalian Nav1.3/SCN3A and Nav1.6/SCN8A sodium channels, as
CC well as insect BgNav1 and VdNav1 sodium channels.
CC {ECO:0000269|PubMed:33368037}.
CC -!- FUNCTION: [Delta-stichotoxin-Hcr1f]: Binds to site 3 of voltage-gated
CC sodium channels and inhibits the inactivation process. Specifically
CC inhibits mammalian Nav1.2/SCN3A (low inhibition) and Nav1.6/SCN8A
CC sodium channels, as well as insect BgNav1 and VdNav1 sodium channels.
CC {ECO:0000269|PubMed:33368037}.
CC -!- SUBUNIT: [Delta-stichotoxin-Hcr1f]: Probably composed of two peptide
CC chains of 12 and 35 residues connected by two disulfide bonds (Cys-3-
CC Cys-43 and Cys-5-Cys-33). {ECO:0000305|PubMed:33368037}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}. Nematocyst.
CC -!- PTM: Delta-SHTX-Hcr1f (RTX-VI) may be the result of post-translational
CC modification of delta-SHTX-Hcr1a (RTX-III), which would consist of Arg-
CC 13 cleavage. {ECO:0000305|PubMed:33368037}.
CC -!- MISCELLANEOUS: [Delta-stichotoxin-Hcr1a]: Is not active on mammalian
CC Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.8/SCN10A
CC sodium channels. {ECO:0000269|PubMed:33368037}.
CC -!- MISCELLANEOUS: [Delta-stichotoxin-Hcr1f]: Is not active on mammalian
CC Nav1.1/SCN1A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.8/SCN10A
CC sodium channels. {ECO:0000269|PubMed:33368037}.
CC -!- SIMILARITY: Belongs to the sea anemone sodium channel inhibitory toxin
CC family. Type II subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P30832; -.
DR SMR; P30832; -.
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 Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Nematocyst; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..48
FT /note="Delta-stichotoxin-Hcr1a"
FT /evidence="ECO:0000269|Ref.1"
FT /id="PRO_0000221524"
FT PEPTIDE 1..12
FT /note="Delta-stichotoxin-Hcr1f"
FT /evidence="ECO:0000269|PubMed:33368037"
FT /id="PRO_0000453742"
FT PEPTIDE 14..48
FT /note="Delta-stichotoxin-Hcr1f"
FT /evidence="ECO:0000269|PubMed:33368037"
FT /id="PRO_0000453743"
FT MOD_RES 48
FT /note="Lysine amide; partial; in Delta-stichotoxin-Hcr1f"
FT /evidence="ECO:0000269|PubMed:33368037"
FT DISULFID 3..43
FT /evidence="ECO:0000269|PubMed:2573358"
FT DISULFID 5..33
FT /evidence="ECO:0000269|PubMed:2573358"
FT DISULFID 26..44
FT /evidence="ECO:0000269|PubMed:2573358"
SQ SEQUENCE 48 AA; 5386 MW; 862C5DDBCFC12A47 CRC64;
GNCKCDDEGP YVRTAPLTGY VDLGYCNEGW EKCASYYSPI AECCRKKK
