ID   NEMA3_RAMPS             Reviewed;          31 AA.
AC   P0DQS5;
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-3 {ECO:0000303|PubMed:29567943};
OS   Ramphogordius pseudolacteus (Ribbon worm).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Nemertea; Pilidiophora;
OC   Heteronemertea; Lineidae; Ramphogordius.
OX   NCBI_TaxID=947579;
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: Toxin with similar potency against both insect and mammalian
CC       sodium channels (Nav) (PubMed:34445875). It inhibits inactivation of
CC       most Nav tested (B.germanica (BgNav1); EC(50)=97.5 nM, hNav1.1/SCN1A;
CC       EC(50)=125.8 nM, rNav1.2/SCN2A; EC(50)=137.8 nM, rNav1.3/SCN3A;
CC       EC(50)=138.9 nM, rNav1.4/SCN4A; EC(50)=150.2 nM, hNav1.5/SCN5A;
CC       EC(50)=108.4 nM, mNav1.6/SCN8A; EC(50)=92.8 nM, hNav1.9/SCN9A;
CC       EC(50)=102.2 nM) (PubMed:34445875). 1 uM is enough to completely
CC       inhibits the inactivation, resulting in sustained non-inactivating
CC       currents (By similarity). In addition, the toxin significantly enhances
CC       the recovery from inactivation, and the open state is not required for
CC       the toxin to interact with the channel (By similarity). In vivo,
CC       injection into brine shrimp (Artemia salina) stops movement or causes
CC       death after 24 hours (EC(50)=4.7 uM) (PubMed:34445875).
CC       {ECO:0000250|UniProtKB:P0DM24, 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-3"
FT                   /evidence="ECO:0000305|PubMed:29567943"
FT                   /id="PRO_0000454426"
FT   MOD_RES         28
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250|UniProtKB:P0DM24"
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;  3251 MW;  7962BBD0335EC86A CRC64;
     GCIKTGSGCT LSKGCCTKNC GWNFKCNPPN Q