TXP1_PARSR
ID TXP1_PARSR Reviewed; 29 AA.
AC P61230;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 25-MAY-2022, entry version 63.
DE RecName: Full=Kappa-theraphotoxin-Ps1a {ECO:0000305};
DE Short=Kappa-TRTX-Ps1a {ECO:0000305};
DE AltName: Full=PaTx1 {ECO:0000303|PubMed:10051143, ECO:0000303|PubMed:15096626};
DE AltName: Full=Phrixotoxin-1 {ECO:0000303|PubMed:10051143, ECO:0000303|PubMed:15096626};
OS Paraphysa scrofa (Chilean copper tarantula) (Phrixotrichus auratus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Paraphysa.
OX NCBI_TaxID=269635;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=10051143; DOI=10.1038/sj.bjp.0702283;
RA Diochot S., Drici M.-D., Moinier D., Fink M., Lazdunski M.;
RT "Effects of phrixotoxins on the Kv4 family of potassium channels and
RT implications for the role of Ito1 in cardiac electrogenesis.";
RL Br. J. Pharmacol. 126:251-263(1999).
RN [2]
RP FUNCTION ON NAV1.7/SCN9A, AND MUTAGENESIS OF ALA-12; LEU-19 AND
RP 28-ILE-ILE-29.
RX PubMed=25026046; DOI=10.1021/jm500687u;
RA Park J.H., Carlin K.P., Wu G., Ilyin V.I., Musza L.L., Blake P.R.,
RA Kyle D.J.;
RT "Studies examining the relationship between the chemical structure of
RT protoxin II and its activity on voltage gated sodium channels.";
RL J. Med. Chem. 57:6623-6631(2014).
RN [3]
RP STRUCTURE BY NMR, SYNTHESIS, DISULFIDE BONDS, AND AMIDATION AT ILE-29.
RX PubMed=15096626; DOI=10.1110/ps.03584304;
RA Chagot B., Escoubas P., Villegas E., Bernard C., Ferrat G., Corzo G.,
RA Lazdunski M., Darbon H.;
RT "Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4
RT potassium channels from the venom of the theraphosid spider Phrixotrichus
RT auratus.";
RL Protein Sci. 13:1197-1208(2004).
CC -!- FUNCTION: Potent and specific blocker of Kv4.2/KCND2 (IC(50)=5 nM) and
CC Kv4.3/KCND3 (IC(50)=28 nM) potassium channels (PubMed:10051143). Acts
CC by altering the gating properties of these channels (PubMed:10051143).
CC Also shows moderate inhibition on human voltage-gated sodium channel
CC Nav1.7/SCN9A activation (IC(50)=423 nM) (PubMed:25026046).
CC {ECO:0000269|PubMed:10051143, ECO:0000269|PubMed:25026046}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10051143}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10051143}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:15096626}.
CC -!- MASS SPECTROMETRY: Mass=3547.60; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10051143};
CC -!- MISCELLANEOUS: This toxin does not inhibit Kv1/KCNA, Kv2/KCNB,
CC Kv3/KCNC, and Kv11/KCNH channels (PubMed:10051143). It weakly blocks
CC the neuronal TTX-sensitive sodium currents of neuroblastoma cells (13%
CC inhibition at 100 nM) (PubMed:10051143). Does not inhibit sodium
CC channel Nav1.2/SCN2A (PubMed:25026046). {ECO:0000269|PubMed:10051143,
CC ECO:0000269|PubMed:25026046}.
CC -!- SIMILARITY: Belongs to the neurotoxin 30 (phrixotoxin) family.
CC {ECO:0000305}.
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DR PDB; 1V7F; NMR; -; A=1-29.
DR PDBsum; 1V7F; -.
DR AlphaFoldDB; P61230; -.
DR SMR; P61230; -.
DR ArachnoServer; AS000399; kappa-theraphotoxin-Ps1a.
DR EvolutionaryTrace; P61230; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium 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; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT PEPTIDE 1..29
FT /note="Kappa-theraphotoxin-Ps1a"
FT /evidence="ECO:0000269|PubMed:10051143"
FT /id="PRO_0000044555"
FT MOD_RES 29
FT /note="Isoleucine amide"
FT /evidence="ECO:0000269|PubMed:15096626"
FT DISULFID 2..16
FT /evidence="ECO:0000269|PubMed:15096626,
FT ECO:0007744|PDB:1V7F"
FT DISULFID 9..21
FT /evidence="ECO:0000269|PubMed:15096626,
FT ECO:0007744|PDB:1V7F"
FT DISULFID 15..25
FT /evidence="ECO:0000269|PubMed:15096626,
FT ECO:0007744|PDB:1V7F"
FT MUTAGEN 12
FT /note="A->E: No change in ability to inhibit Nav1.7/SCN9A,
FT and gain of ability to inhibit Nav1.2/SCN2A (IC(50)=919
FT nM); when associated with M-19."
FT /evidence="ECO:0000269|PubMed:25026046"
FT MUTAGEN 19
FT /note="L->M: No change in ability to inhibit Nav1.7/SCN9A,
FT and gain of ability to inhibit Nav1.2/SCN2A (IC(50)=919
FT nM); when associated with E-12."
FT /evidence="ECO:0000269|PubMed:25026046"
FT MUTAGEN 28..29
FT /note="II->KLW: 400-fold increase in ability to inhibit
FT Nav1.7/SCN9A; and important gain of ability to inhibit
FT Nav1.2/SCN2A (IC(50)=24 nM)."
FT /evidence="ECO:0000269|PubMed:25026046"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:1V7F"
SQ SEQUENCE 29 AA; 3555 MW; 3B80CAB68C1B9B36 CRC64;
YCQKWMWTCD SARKCCEGLV CRLWCKKII
