ID   ISTX_IXOSC              Reviewed;          88 AA.
AC   Q4PN35;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   25-MAY-2022, entry version 30.
DE   RecName: Full=Sodium channel inhibitor ISTX-I {ECO:0000303|PubMed:27407029};
DE   Flags: Precursor;
OS   Ixodes scapularis (Black-legged tick) (Deer tick).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC   Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Ixodinae; Ixodes.
OX   NCBI_TaxID=6945;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Salivary gland;
RX   PubMed=16431279; DOI=10.1016/j.ibmb.2005.11.005;
RA   Ribeiro J.M.C., Alarcon-Chaidez F., Francischetti I.M.B., Mans B.J.,
RA   Mather T.N., Valenzuela J.G., Wikel S.K.;
RT   "An annotated catalog of salivary gland transcripts from Ixodes scapularis
RT   ticks.";
RL   Insect Biochem. Mol. Biol. 36:111-129(2006).
RN   [2] {ECO:0007744|PDB:2NDI}
RP   STRUCTURE BY NMR OF 42-86, RECOMBINANT EXPRESSION, DISULFIDE BONDS, AND
RP   FUNCTION.
RX   PubMed=27407029; DOI=10.1038/srep29691;
RA   Rong M., Liu J., Zhang M., Wang G., Zhao G., Wang G., Zhang Y., Hu K.,
RA   Lai R.;
RT   "A sodium channel inhibitor ISTX-I with a novel structure provides a new
RT   hint at the evolutionary link between two toxin folds.";
RL   Sci. Rep. 6:29691-29691(2016).
CC   -!- FUNCTION: By inhibiting Nav1.7/SCN9A sodium channel, may prevent signal
CC       transmission caused by tick penetration and the blood taken, allowing
CC       the tick to avoid discovery (PubMed:27407029). Weakly and specifically
CC       inhibits Nav1.7/SCN9A (IC(50)=1.6 uM) (PubMed:27407029). Significantly
CC       shifts the steady-state inactivation curve of the Nav1.7/SCN9A in the
CC       hyperpolarized direction (PubMed:27407029). Does not induce changes to
CC       I-V curve and conductance-voltage relationship (PubMed:27407029).
CC       {ECO:0000269|PubMed:27407029}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:27407029}.
CC   -!- TISSUE SPECIFICITY: Expressed by the salivary glands.
CC       {ECO:0000305|PubMed:27407029}.
CC   -!- DOMAIN: Adopts a novel structural fold that may be an intermediate
CC       scaffold between disulfide-directed hairpin (DDH) and the inhibitor
CC       cystine knot motif (ICK). {ECO:0000269|PubMed:27407029}.
CC   -!- MISCELLANEOUS: Shows very weak or no effect on human Nav1.1/SCN1A,
CC       Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, hNav1.5/SCN5A, and
CC       Nav1.6/SCN8A sodium channels (PubMed:27407029). Does not show obvious
CC       effects on potassium and calcium channels (PubMed:27407029).
CC       {ECO:0000269|PubMed:27407029}.
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DR   EMBL; DQ065938; AAY66575.1; -; mRNA.
DR   PDB; 2NDI; NMR; -; A=42-86.
DR   PDBsum; 2NDI; -.
DR   AlphaFoldDB; Q4PN35; -.
DR   BMRB; Q4PN35; -.
DR   SMR; Q4PN35; -.
DR   VEuPathDB; VectorBase:ISCW024638; -.
DR   Proteomes; UP000001555; Unplaced.
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   3D-structure; Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW   Reference proteome; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..88
FT                   /note="Sodium channel inhibitor ISTX-I"
FT                   /evidence="ECO:0000305|PubMed:27407029"
FT                   /id="PRO_5004241964"
FT   DISULFID        43..55
FT                   /evidence="ECO:0000269|PubMed:27407029,
FT                   ECO:0007744|PDB:2NDI"
FT   DISULFID        49..69
FT                   /evidence="ECO:0000269|PubMed:27407029,
FT                   ECO:0007744|PDB:2NDI"
FT   DISULFID        54..79
FT                   /evidence="ECO:0000269|PubMed:27407029,
FT                   ECO:0007744|PDB:2NDI"
FT   STRAND          51..58
FT                   /evidence="ECO:0007829|PDB:2NDI"
FT   STRAND          61..63
FT                   /evidence="ECO:0007829|PDB:2NDI"
FT   STRAND          66..70
FT                   /evidence="ECO:0007829|PDB:2NDI"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:2NDI"
SQ   SEQUENCE   88 AA;  9233 MW;  5835958E2F6CD123 CRC64;
     MNKFTVALVS TLLLGMLRIT VSAQPLENEA VSADEPSAGG KLCSENGDCA ADECCVDTVF
     EGDMVTRSCE KTTGNFTECP GLTPIAKK