TX3_PARSR
ID TX3_PARSR Reviewed; 34 AA.
AC P84510;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 1.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=Beta-theraphotoxin-Ps1a {ECO:0000305};
DE Short=Beta-TRTX-Ps1a {ECO:0000305};
DE AltName: Full=PaurTx-III {ECO:0000303|PubMed:29703751};
DE AltName: Full=Phrixotoxin-3 {ECO:0000303|PubMed:16267209};
DE Short=PaurTx3 {ECO:0000303|PubMed:16267209, ECO:0000303|PubMed:28805686};
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, BIOASSAY, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=16267209; DOI=10.1124/mol.105.015941;
RA Bosmans F., Rash L., Zhu S., Diochot S., Lazdunski M., Escoubas P.,
RA Tytgat J.;
RT "Four novel tarantula toxins as selective modulators of voltage-gated
RT sodium channel subtypes.";
RL Mol. Pharmacol. 69:419-429(2006).
RN [2]
RP FUNCTION, AND SYNTHESIS.
RX PubMed=29703751; DOI=10.1074/jbc.ra118.002553;
RA Agwa A.J., Peigneur S., Chow C.Y., Lawrence N., Craik D.J., Tytgat J.,
RA King G.F., Henriques S.T., Schroeder C.I.;
RT "Gating modifier toxins isolated from spider venom: modulation of voltage-
RT gated sodium channels and the role of lipid membranes.";
RL J. Biol. Chem. 293:9041-9052(2018).
RN [3]
RP STRUCTURE BY NMR, DISULFIDE BOND, AND SYNTHESIS.
RX PubMed=28805686; DOI=10.3390/toxins9080248;
RA Agwa A.J., Huang Y.H., Craik D.J., Henriques S.T., Schroeder C.I.;
RT "Lengths of the C-terminus and interconnecting loops impact stability of
RT spider-derived gating modifier toxins.";
RL Toxins 9:248-262(2017).
CC -!- FUNCTION: Potent inhibitor of Nav1.2/SCN2A voltage-gated sodium
CC channels (IC(50)=0.6-0.7 nM) (PubMed:16267209, PubMed:29703751). Also
CC weakly inhibits Nav1.1/SCN1A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.7/SCN9A
CC and Nav1.8/SCN10A (IC(50)=20-610 nM) (PubMed:16267209,
CC PubMed:29703751). It acts by shifting the voltage dependence of channel
CC activation to more depolarized potentials and by blocking the inward
CC component of the sodium current (PubMed:16267209). It shows low
CC affinity for lipid bilayers (PubMed:29703751). In vivo, this toxin
CC causes general ataxia, lack of response to stimuli, and semiparalysis
CC (PubMed:16267209). After a few minutes, the mice are unable to stand,
CC and breathing is reduced in rhythm and intensity (PubMed:16267209).
CC Symptoms gradually increase with progressive slowing of breathing and
CC flaccid paralysis; death occurred within 10 to 20 minutes post
CC injection (PubMed:16267209). Animals remain totally flaccid, and no
CC symptoms of excitatory neurotoxicity are observed (PubMed:16267209).
CC {ECO:0000269|PubMed:16267209, ECO:0000269|PubMed:29703751}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16267209}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:16267209}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:28805686}.
CC -!- MASS SPECTROMETRY: Mass=4055.88; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:16267209};
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 08 (Gtx1-15)
CC subfamily. {ECO:0000305}.
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DR PDB; 5WE3; NMR; -; A=1-34.
DR PDBsum; 5WE3; -.
DR AlphaFoldDB; P84510; -.
DR BMRB; P84510; -.
DR SMR; P84510; -.
DR TCDB; 8.B.3.1.4; the huwentoxin-1 (huwentoxin-1) family.
DR ArachnoServer; AS000274; beta-theraphotoxin-Ps1a.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0044489; P:negative regulation of voltage-gated sodium channel activity in another organism; IDA:UniProtKB.
DR InterPro; IPR011696; Huwentoxin-1.
DR InterPro; IPR013140; Huwentoxin_CS1.
DR Pfam; PF07740; Toxin_12; 1.
DR PROSITE; PS60021; HWTX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT PEPTIDE 1..34
FT /note="Beta-theraphotoxin-Ps1a"
FT /evidence="ECO:0000269|PubMed:16267209"
FT /id="PRO_0000045003"
FT DISULFID 2..17
FT /evidence="ECO:0000269|PubMed:28805686,
FT ECO:0000312|PDB:5WE3"
FT DISULFID 9..23
FT /evidence="ECO:0000269|PubMed:28805686,
FT ECO:0000312|PDB:5WE3"
FT DISULFID 16..30
FT /evidence="ECO:0000269|PubMed:28805686,
FT ECO:0000312|PDB:5WE3"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:5WE3"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:5WE3"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:5WE3"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:5WE3"
SQ SEQUENCE 34 AA; 4066 MW; D0A84E067E0F8D5E CRC64;
DCLGFLWKCN PSNDKCCRPN LVCSRKDKWC KYQI
