ID   TX1A_PELMU              Reviewed;          85 AA.
AC   P0DQV4;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   03-AUG-2022, sequence version 1.
DT   03-AUG-2022, entry version 1.
DE   RecName: Full=Delta/kappa-theraphotoxin-Pm1a {ECO:0000303|PubMed:35074873};
DE            Short=Delta/kappa-TRTX-Pm1a {ECO:0000303|PubMed:35074873};
DE   Flags: Precursor;
OS   Pelinobius muticus (King baboon spider) (Citharischius crawshayi).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Pelinobius.
OX   NCBI_TaxID=753628;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOASSAY, SUBCELLULAR LOCATION,
RP   STRUCTURE BY NMR OF 44-85, DISULFIDE BONDS, SYNTHESIS OF 44-85, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=35074873; DOI=10.1073/pnas.2110932119;
RA   Finol-Urdaneta R.K., Ziegman R., Dekan Z., McArthur J.R., Heitmann S.,
RA   Luna-Ramirez K., Tae H.S., Mueller A., Starobova H., Chin Y.K.,
RA   Wingerd J.S., Undheim E.A.B., Cristofori-Armstrong B., Hill A.P.,
RA   Herzig V., King G.F., Vetter I., Rash L.D., Adams D.J., Alewood P.F.;
RT   "Multitarget nociceptor sensitization by a promiscuous peptide from the
RT   venom of the King Baboon spider.";
RL   Proc. Natl. Acad. Sci. U.S.A. 119:0-0(2022).
CC   -!- FUNCTION: Multimodal toxin that enhances nociceptor excitability mainly
CC       by the simultaneous stimulation of repetitive firing (through
CC       Nav1.8/SCN10A channel current enhancement) and impairment of
CC       repolarization (by inhibiting delayed rectifier current of
CC       Kv2.1/KCNB1), with a potential contribution from tetrodotoxin-sensitive
CC       voltage-gated sodium channels (Nav) modified excitability. Enhances
CC       Nav1.8/SCN10A currents (EC(50)=1.1 uM), modifies the channel gating by
CC       a right-shift in steady-state inactivation and delays open-state
CC       inactivation. Also decreases Kv2.1/KCNB1 currents (IC(50)=0.43 uM) and
CC       causes a depolarizing shift in the voltage dependence of activation
CC       without change in steady-state inactivation. In addition, inhibits peak
CC       currents of human sodium channels (Nav1.1 to Nav1.7, IC(50)=0.38-2.3
CC       uM) and delays fast inactivation of Nav1.1/SCN1A, Nav1.3/SCN3A,
CC       Nav1.6/SCN8A, and Nav1.7/SCN9A. In small dorsal root ganglion neurons,
CC       induces hyperexcitability by enhancing tetrodotoxin-resistant sodium
CC       currents, impairing repolarization and lowering the threshold of action
CC       potential firing, consistent with the severe pain associated with
CC       envenomation. In vivo, elicits nocifensive behavior in mice after
CC       intraplantar injection. {ECO:0000269|PubMed:35074873}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:35074873}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:35074873}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:35074873}.
CC   -!- MASS SPECTROMETRY: Mass=4524.5; Method=MALDI; Note=Monoisotopic mass.;
CC       Evidence={ECO:0000269|PubMed:35074873};
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family.
CC       {ECO:0000305}.
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PE   1: Evidence at protein level;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW   Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW   Voltage-gated potassium channel impairing toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..43
FT                   /evidence="ECO:0000305|PubMed:35074873"
FT                   /id="PRO_0000456296"
FT   CHAIN           44..85
FT                   /note="Delta/kappa-theraphotoxin-Pm1a"
FT                   /evidence="ECO:0000305|PubMed:35074873"
FT                   /id="PRO_0000456297"
FT   DISULFID        50..64
FT                   /evidence="ECO:0000269|PubMed:35074873"
FT   DISULFID        57..69
FT                   /evidence="ECO:0000269|PubMed:35074873"
FT   DISULFID        63..77
FT                   /evidence="ECO:0000269|PubMed:35074873"
SQ   SEQUENCE   85 AA;  9224 MW;  C9BF23553BCF771E CRC64;
     MKTFVFIVLV ALAFVLTAAK EERANPSELV SALAELVMLD AERGVDKPGC RYLFGGCKSD
     DDCCPRLGCK GKGHDYCAWD GTFSD