ID   PE1B_PHOEV              Reviewed;          34 AA.
AC   P0DQN2;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 1.
DT   25-MAY-2022, entry version 6.
DE   RecName: Full=Beta/mu-theraphotoxin-Pe1b {ECO:0000303|PubMed:32511987};
DE            Short=Beta/mu-TRTX-Pe1b {ECO:0000303|PubMed:32511987};
OS   Phormingochilus everetti (Malaysian purple earth tiger tarantula).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Phormingochilus.
OX   NCBI_TaxID=2751878;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, RECOMBINANT EXPRESSION,
RP   AND MUTAGENESIS OF GLU-17; SER-20; 23-PRO--HIS-26 AND PHE-34.
RC   TISSUE=Venom;
RX   PubMed=32511987; DOI=10.1016/j.bcp.2020.114080;
RA   Rupasinghe D.B., Herzig V., Vetter I., Dekan Z., Gilchrist J., Bosmans F.,
RA   Alewood P.F., Lewis R.J., King G.F.;
RT   "Mutational analysis of ProTx-I and the novel venom peptide Pe1b provide
RT   insight into residues responsible for selective inhibition of the analgesic
RT   drug target NaV1.7.";
RL   Biochem. Pharmacol. 181:114080-114080(2020).
CC   -!- FUNCTION: Ion channel impairing toxin that inhibits several voltage-
CC       gated sodium channels. It acts by inhibiting the inward component of
CC       the sodium current and by shifting the voltage dependence of channel
CC       activation to more depolarized potentials (PubMed:32511987). Its most
CC       potent activity is on Nav1.7/SCN9A (IC(50)=167 nM), followed by
CC       Nav1.6/SCN8A (IC(50)=696 nM), and Nav1.2/SCN2A (IC(50)=3.54 uM)
CC       (PubMed:32511987). {ECO:0000269|PubMed:32511987}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32511987}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:32511987}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P83480}.
CC   -!- MISCELLANEOUS: The recombinant toxin does not show or very weak
CC       activity on Nav1.5/SCN5A (IC(50)>10 uM). {ECO:0000269|PubMed:32511987}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 54 (ProTx-1)
CC       subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   AlphaFoldDB; P0DQN2; -.
DR   SMR; P0DQN2; -.
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   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Knottin; Neurotoxin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..34
FT                   /note="Beta/mu-theraphotoxin-Pe1b"
FT                   /id="PRO_0000451452"
FT   DISULFID        2..16
FT                   /evidence="ECO:0000250|UniProtKB:P83480"
FT   DISULFID        9..21
FT                   /evidence="ECO:0000250|UniProtKB:P83480"
FT   DISULFID        15..28
FT                   /evidence="ECO:0000250|UniProtKB:P83480"
FT   MUTAGEN         17
FT                   /note="E->K: No change in ability to inhibit Nav1.2/SCN2A,
FT                   14-fold increase in ability to inhibit Nav1.5/SCN5A, and 3-
FT                   fold increase in ability to inhibit Nav1.7/SCN9A."
FT                   /evidence="ECO:0000269|PubMed:32511987"
FT   MUTAGEN         20
FT                   /note="S->V: 4.6-fold increase in ability to inhibit
FT                   Nav1.2/SCN2A, and no change in ability to inhibit both
FT                   Nav1.5/SNC5A and Nav1.7/SCN9A."
FT                   /evidence="ECO:0000269|PubMed:32511987"
FT   MUTAGEN         23..26
FT                   /note="PKWH->RRHG: Pe1b-L4; dramatic increase in ability to
FT                   inhibit Nav1.2/SCN2A, moderate increase in ability to
FT                   inhibit Nav1.5/SCN5A, and no change in ability to inhibit
FT                   Nav1.7/SCN9A."
FT                   /evidence="ECO:0000269|PubMed:32511987"
FT   MUTAGEN         34
FT                   /note="F->FS: 6-fold increase in ability to inhibit
FT                   Nav1.2/SCN2A, and no change in ability to inhibit both
FT                   Nav1.5/SCN5A and Nav1.7/SCN9A."
FT                   /evidence="ECO:0000269|PubMed:32511987"
SQ   SEQUENCE   34 AA;  3982 MW;  4C1093A5CE1CD2EB CRC64;
     ECRYWLGGCS KTGDCCEHLS CSPKWHWCVW DGTF