ID   NTA_PSARE               Reviewed;          35 AA.
AC   A0A1S4NYE8; A0A218K9X1;
DT   30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2017, sequence version 2.
DT   25-MAY-2022, entry version 14.
DE   RecName: Full=Beta/delta-theraphotoxin-Pre1a {ECO:0000303|PubMed:28428547};
DE            Short=Beta/delta-TRTX-Pre1a {ECO:0000303|PubMed:28428547};
OS   Psalmopoeus reduncus (Costa Rican orangemouth tarantula).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Psalmopoeus.
OX   NCBI_TaxID=1795668;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, SYNTHESIS, MASS
RP   SPECTROMETRY, DISULFIDE BONDS, AND 3D-STRUCTURE MODELING.
RC   TISSUE=Venom;
RX   PubMed=28428547; DOI=10.1038/s41598-017-01129-0;
RA   Wingerd J.S., Mozar C.A., Ussing C.A., Murali S.S., Chin Y.K.,
RA   Cristofori-Armstrong B., Durek T., Gilchrist J., Vaughan C.W., Bosmans F.,
RA   Adams D.J., Lewis R.J., Alewood P.F., Mobli M., Christie M.J., Rash L.D.;
RT   "The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance of the
RT   S1-S2 voltage-sensor region for sodium channel subtype selectivity.";
RL   Sci. Rep. 7:974-988(2017).
RN   [2] {ECO:0000312|PDB:5I1X, ECO:0000312|PDB:5I2P}
RP   STRUCTURE BY NMR OF MUTANTS ALA-6 AND ALA-7.
RA   Chin Y.K.-Y., Wingerd J.S., Mobli M., Rash L.D.;
RT   "Resonance assignments and NMR structure determination of tarantula toxin,
RT   mu-TRTX-Pre1a.";
RL   Submitted (FEB-2016) to the PDB data bank.
CC   -!- FUNCTION: Gating-modifier toxin that both inhibits the peak current of
CC       human Nav1.1/SCN1A, rat Nav1.2/SCN2A, human Nav1.6/SCN8A, and human
CC       Nav1.7/SCN9A and concurrently inhibits fast inactivation of human
CC       Nav1.1 and rat Nav1.3/SCN3A. The relative rank order potency for Nav
CC       modulation is Nav1.3 (inactivation EC(50)=45 nM) > Nav1.7 > Nav1.2 >
CC       Nav1.1 (inactivation) > Nav1.1 > Nav1.6 > Nav1.3 (IC(50)=8 uM). The DII
CC       and DIV S3-S4 loops of Nav channel voltage sensors are important for
CC       the interaction of this toxin with Nav channels but cannot account for
CC       its unique subtype selectivity. It is the variability of the S1-S2
CC       loops between NaV channels which contributes substantially to the
CC       selectivity profile observed for this toxin, particularly with regards
CC       to fast inactivation. This toxin may bind the channel in the resting
CC       state (Probable). {ECO:0000269|PubMed:28428547,
CC       ECO:0000305|PubMed:28428547}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28428547}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:28428547}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000305|Ref.2}.
CC   -!- MASS SPECTROMETRY: Mass=4227.5; Method=MALDI; Note=Monoisotopic mass.;
CC       Evidence={ECO:0000269|PubMed:28428547};
CC   -!- MISCELLANEOUS: NMR structure determination (PDB 5I1X) is done on a
CC       mutant of 36 residues with an additional Ser at first position and an
CC       Ala residue replacing the Phe-7. Functional information is not known on
CC       this mutant. {ECO:0000305|Ref.2}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family.
CC       {ECO:0000305}.
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DR   PDB; 5I1X; NMR; -; A=1-35.
DR   PDB; 5I2P; NMR; -; A=1-35.
DR   PDBsum; 5I1X; -.
DR   PDBsum; 5I2P; -.
DR   AlphaFoldDB; A0A1S4NYE8; -.
DR   BMRB; A0A1S4NYE8; -.
DR   SMR; A0A1S4NYE8; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR011696; Huwentoxin-1.
DR   Pfam; PF07740; Toxin_12; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..35
FT                   /note="Beta/delta-theraphotoxin-Pre1a"
FT                   /evidence="ECO:0000269|PubMed:28428547"
FT                   /id="PRO_0000441255"
FT   SITE            7
FT                   /note="Probable key residue for the interaction with Nav
FT                   channels"
FT                   /evidence="ECO:0000305|PubMed:28428547"
FT   DISULFID        3..18
FT                   /evidence="ECO:0000269|PubMed:28428547, ECO:0000305|Ref.2"
FT   DISULFID        10..23
FT                   /evidence="ECO:0000269|PubMed:28428547, ECO:0000305|Ref.2"
FT   DISULFID        17..30
FT                   /evidence="ECO:0000269|PubMed:28428547, ECO:0000305|Ref.2"
FT   STRAND          12..14
FT                   /evidence="ECO:0007829|PDB:5I1X"
FT   STRAND          19..24
FT                   /evidence="ECO:0007829|PDB:5I1X"
FT   TURN            25..28
FT                   /evidence="ECO:0007829|PDB:5I1X"
FT   STRAND          29..33
FT                   /evidence="ECO:0007829|PDB:5I1X"
SQ   SEQUENCE   35 AA;  4236 MW;  57B5B33E4C113CEC CRC64;
     EDCLGWFSRC SPKNDKCCPN YKCSSKDLWC KYKIW