ID   NEMA2_LINRU             Reviewed;          31 AA.
AC   P0DQS3;
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-2 {ECO:0000303|PubMed:29567943};
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   PROTEIN SEQUENCE, MASS SPECTROMETRY, AND HYDROXYLATION AT PRO-28 AND
RP   PRO-29.
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). Delays the inactivation of
CC       most Nav channels tested (B.germanica (BgNav1); EC(50)=87.2 nM,
CC       hNav1.1/SCN1A; EC(50)=125.8 nM, rNav1.2/SCN2A; EC(50)=97.9 nM,
CC       rNav1.3/SCN3A; EC(50)=127.7 nM, rNav1.4/SCN4A; EC(50)=1150.3 nM,
CC       hNav1.5/SCN5A; EC(50)=149.2 nM, mNav1.6/SCN8A; EC(50)=1361.8 nM,
CC       hNav1.9/SCN9A; EC(50)=1296.7 nM) (PubMed:34445875). 1 uM is enough to
CC       completely inhibits the inactivation, resulting in sustained non-
CC       inactivating currents (By similarity). In addition, the toxin
CC       significantly enhances the recovery from inactivation, and the open
CC       state is not required for the toxin to interact with the channel (By
CC       similarity). In vivo, injection into brine shrimp (Artemia salina)
CC       stops movement or causes death after 24 hours (EC(50)=2.9 uM)
CC       (PubMed:34445875). {ECO:0000250|UniProtKB:P0DM24,
CC       ECO:0000269|PubMed:34445875}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:29567943}.
CC   -!- TISSUE SPECIFICITY: Confined to the epidermis and to the mucus layer.
CC       {ECO:0000269|PubMed:29567943}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000305|PubMed:29567943}.
CC   -!- MASS SPECTROMETRY: Mass=3260.738; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:29567943};
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   SMR; P0DQS3; -.
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   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Hydroxylation;
KW   Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..31
FT                   /note="Nemertide alpha-2"
FT                   /evidence="ECO:0000269|PubMed:29567943"
FT                   /id="PRO_0000454424"
FT   MOD_RES         28
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:29567943"
FT   MOD_RES         29
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:29567943"
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;  3236 MW;  2863BBDA93F4C876 CRC64;
     GCIATGSVCT LSKGCCTKNC GWNFKCNPPN Q