ID   NEMA8_RISOC             Reviewed;          27 AA.
AC   P0DQT0;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 1.
DT   03-AUG-2022, entry version 2.
DE   RecName: Full=Nemertide alpha-8 {ECO:0000303|PubMed:34445875};
DE   Flags: Fragment;
OS   Riseriellus occultus (Ribbon worm).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Nemertea; Pilidiophora;
OC   Heteronemertea; Lineidae; Riseriellus.
OX   NCBI_TaxID=88934;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=29567943; DOI=10.1038/s41598-018-22305-w;
RA   Jacobsson E., Andersson H.S., Strand M., Peigneur S., Eriksson C.,
RA   Loden H., Shariatgorji M., Andren P.E., Lebbe E.K.M., Rosengren K.J.,
RA   Tytgat J., Goeransson U.;
RT   "Peptide ion channel toxins from the bootlace worm, the longest animal on
RT   Earth.";
RL   Sci. Rep. 8:4596-4596(2018).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=34445875; DOI=10.1021/acs.jnatprod.1c00104;
RA   Jacobsson E., Peigneur S., Andersson H.S., Laborde Q., Strand M.,
RA   Tytgat J., Goeransson U.;
RT   "Functional characterization of the nemertide alpha family of peptide
RT   toxins.";
RL   J. Nat. Prod. 84:2121-2128(2021).
CC   -!- FUNCTION: Highly potent toxin against both insect and some mammalian
CC       sodium channels (Nav). It potently inhibits inactivation of insect
CC       sodium channels of B.germanica (BgNav1) and also delays the
CC       inactivation of mammalian Nav with potent activity on Nav1.3/SCN3A and
CC       Nav1.4/SCN4A (By similarity). 1 uM is enough to completely inhibits the
CC       inactivation, resulting in sustained non-inactivating currents. In
CC       addition, the toxin significantly enhances the recovery from
CC       inactivation, and the open state is not required for the toxin to
CC       interact with the channel (By similarity). In vivo, injection into
CC       brine shrimp (Artemia salina) stops movement or causes death after 24
CC       hours (EC(50)=0.4 uM) (By similarity). {ECO:0000250|UniProtKB:P0DM24,
CC       ECO:0000250|UniProtKB:P0DQS7}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0DM24}.
CC   -!- TISSUE SPECIFICITY: Confined to the epidermis and to the mucus layer.
CC       {ECO:0000250|UniProtKB:P0DM24}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P0DM24}.
CC   -!- MISCELLANEOUS: Does not shows effect on rat Nav1.8/SCN10A.
CC       {ECO:0000269|PubMed:34445875}.
CC   -!- SIMILARITY: Belongs to the nemertide family. {ECO:0000305}.
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DR   GO; GO:0005576; C:extracellular region; 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.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Hydroxylation; Ion channel impairing toxin; Knottin;
KW   Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..>27
FT                   /note="Nemertide alpha-8"
FT                   /evidence="ECO:0000305|PubMed:29567943"
FT                   /id="PRO_0000454431"
FT   SITE            8
FT                   /note="Hydrophobic/aromatic residue important for potent
FT                   activity"
FT                   /evidence="ECO:0000305|PubMed:34445875"
FT   DISULFID        2..16
FT                   /evidence="ECO:0000250|UniProtKB:P0DM24"
FT   DISULFID        9..20
FT                   /evidence="ECO:0000250|UniProtKB:P0DM24"
FT   DISULFID        15..26
FT                   /evidence="ECO:0000250|UniProtKB:P0DM24"
FT   NON_TER         27
FT                   /evidence="ECO:0000305|PubMed:29567943"
SQ   SEQUENCE   27 AA;  2790 MW;  B3F4C68BD0DE9BBE CRC64;
     GCIATGSFCT LSKGCCTKNC GWNFACN