ID   NEMA7_LINRU             Reviewed;          31 AA.
AC   P0DQS9;
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-7 {ECO:0000303|PubMed:34445875};
OS   Lineus ruber (Red bootlace) (Poseidon ruber).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Nemertea; Pilidiophora;
OC   Heteronemertea; Lineidae; Lineus.
OX   NCBI_TaxID=88926;
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], SYNTHESIS, FUNCTION, AND BIOASSAY.
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: Potent toxin against insect sodium channel (Nav) and 5- to
CC       100-fold less potent against mammalian sodium channels (By similarity).
CC       Potently inhibits inactivation of insect sodium channels of B.germanica
CC       (BgNav1) (EC(50)=9.5 nM) (PubMed:34445875). The toxin also delays the
CC       inactivation of most mammalian Nav (hNav1.1/SCN1A; EC(50)=171.5 nM,
CC       rNav1.2/SCN2A; EC(50)=50.4 nM, rNav1.3/SCN3A; EC(50)=170.2 nM,
CC       rNav1.4/SCN4A; EC(50)=810.6 nM, hNav1.5/SCN5A; EC(50)=155.6 nM,
CC       mNav1.6/SCN8A; EC(50)=147.6 nM, hNav1.9/SCN9A; EC(50)=129 nM)
CC       (PubMed:34445875). 1 uM is enough to completely inhibits the
CC       inactivation, resulting in sustained non-inactivating currents (By
CC       similarity). In addition, the toxin significantly enhances the recovery
CC       from 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)=6.1 uM) (PubMed:34445875). {ECO:0000250|UniProtKB:P0DM24,
CC       ECO:0000269|PubMed:34445875}.
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   3: Inferred from homology;
KW   Disulfide bond; Hydroxylation; Ion channel impairing toxin; Knottin;
KW   Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..31
FT                   /note="Nemertide alpha-7"
FT                   /evidence="ECO:0000305|PubMed:29567943"
FT                   /id="PRO_0000454430"
FT   MOD_RES         29
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250|UniProtKB:P0DM24"
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"
SQ   SEQUENCE   31 AA;  3318 MW;  29C8BF4846437AB7 CRC64;
     GCIPVGSMCT ISNGCCTKNC GWNFHCNKPN Q