ID   PME2A_POEME             Reviewed;          33 AA.
AC   P0DQO1;
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=Mu/delta-theraphotoxin-Pm2a {ECO:0000303|PubMed:32092883};
DE            Short=Mu/delta-TRTX-Pm2a {ECO:0000303|PubMed:32092883};
DE   AltName: Full=Delta/mu-theraphotoxin-Pm2a {ECO:0000305};
OS   Poecilotheria metallica (Metallic blue ornamental tree spider).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Poecilotheria.
OX   NCBI_TaxID=1956341;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, AMIDATION AT PHE-33,
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-21.
RC   TISSUE=Venom;
RX   PubMed=32092883; DOI=10.3390/biomedicines8020037;
RA   Yin K., Deuis J.R., Dekan Z., Jin A.H., Alewood P.F., King G.F., Herzig V.,
RA   Vetter I.;
RT   "Addition of K22 converts spider venom peptide Pme2a from an activator to
RT   an inhibitor of Nav1.7.";
RL   Biomedicines 8:0-0(2020).
CC   -!- FUNCTION: Gating-modifier toxin with very weak activity on Nav1.7/SCN9A
CC       and Nav1.8/SCN10A. Shows 22% peak current inhibition (at 10 uM) on
CC       Nav1.8/SCN10A sodium channels. Show peak current inhibition and delays
CC       fast inactivation on Nav1.7/SCN9A (EC(50)>10 uM).
CC       {ECO:0000269|PubMed:32092883}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32092883}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:32092883}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P60992}.
CC   -!- MASS SPECTROMETRY: Mass=38017.5; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:32092883};
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 47 subfamily.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; P0DQO1; -.
DR   SMR; P0DQO1; -.
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   Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..33
FT                   /note="Mu/delta-theraphotoxin-Pm2a"
FT                   /evidence="ECO:0000269|PubMed:32092883"
FT                   /id="PRO_0000451633"
FT   MOD_RES         33
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:32092883"
FT   DISULFID        2..16
FT                   /evidence="ECO:0000250|UniProtKB:P60992"
FT   DISULFID        9..21
FT                   /evidence="ECO:0000250|UniProtKB:P60992"
FT   DISULFID        15..27
FT                   /evidence="ECO:0000250|UniProtKB:P60992"
FT   MUTAGEN         21
FT                   /note="C->CK: Increase in ability to inhibit Nav1.7/SCN9A
FT                   and loss of ability to inhibit inactivation."
FT                   /evidence="ECO:0000269|PubMed:32092883"
SQ   SEQUENCE   33 AA;  3817 MW;  F2EBC48D6BA25FC1 CRC64;
     GCTKFMGSCK TDADCCEHLE CYKYKWCGWD GTF