HPR3_THRPR
ID HPR3_THRPR Reviewed; 33 AA.
AC P0DL64;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 25-MAY-2022, entry version 14.
DE RecName: Full=Mu-theraphotoxin-Tp1a {ECO:0000303|PubMed:25979003};
DE Short=Mu-TRTX-Tp1a {ECO:0000303|PubMed:25979003};
DE AltName: Full=Protoxin III {ECO:0000303|PubMed:25979003};
DE Short=ProTx-III {ECO:0000303|PubMed:25979003};
OS Thrixopelma pruriens (Peruvian green velvet tarantula).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Thrixopelma.
OX NCBI_TaxID=213387;
RN [1]
RP PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, SUBCELLULAR LOCATION, STRUCTURE BY
RP NMR, DISULFIDE BOND, AMIDATION AT ILE-33, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=25979003; DOI=10.1124/mol.115.098178;
RA Cardoso F.C., Dekan Z., Rosengren K.J., Erickson A., Vetter I., Deuis J.R.,
RA Herzig V., Alewood P.F., King G.F., Lewis R.J.;
RT "Identification and characterization of ProTx-III [mu-TRTX-Tp1a], a new
RT voltage-gated sodium channel inhibitor from venom of the tarantula
RT Thrixopelma pruriens.";
RL Mol. Pharmacol. 88:291-303(2015).
CC -!- FUNCTION: Inhibits voltage-gated sodium channels without significantly
CC altering the voltage dependence of activation or inactivation. The
CC toxin preferentially inhibits hNav1.7/SCN9A (IC(50)=2.1 nM) >
CC hNav1.6/SCN8A > hNav1.2/SCN2A > hNav1.1/SCN1A > hNav1.3/SCN3A channels
CC in fluorescent assays. The toxin exhibits analgesic properties by
CC reversing spontaneous pain induced in mice by intraplantar injection
CC with OD1 (AC P84646), a scorpion toxin that potentiates hNav1.7/SCN9A.
CC {ECO:0000269|PubMed:25979003}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25979003}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:25979003}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000305|PubMed:25979003}.
CC -!- MASS SPECTROMETRY: Mass=3799; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:25979003};
CC -!- MISCELLANEOUS: Does not affect human voltage-gated calcium channels
CC (Cav) or nicotinic acetylcholine receptors (nAChR) at 5 uM.
CC {ECO:0000269|PubMed:25979003}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 55 (ProTx-
CC III) subfamily. {ECO:0000305}.
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DR PDB; 2MXM; NMR; -; A=1-32.
DR PDBsum; 2MXM; -.
DR AlphaFoldDB; P0DL64; -.
DR BMRB; P0DL64; -.
DR SMR; P0DL64; -.
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 3D-structure; 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-theraphotoxin-Tp1a"
FT /evidence="ECO:0000269|PubMed:25979003"
FT /id="PRO_0000435164"
FT MOD_RES 33
FT /note="Isoleucine amide"
FT /evidence="ECO:0000269|PubMed:25979003"
FT DISULFID 2..17
FT /evidence="ECO:0000269|PubMed:25979003"
FT DISULFID 9..22
FT /evidence="ECO:0000269|PubMed:25979003"
FT DISULFID 16..29
FT /evidence="ECO:0000269|PubMed:25979003"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:2MXM"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2MXM"
SQ SEQUENCE 33 AA; 3809 MW; 41C8B76C25329313 CRC64;
DCLKFGWKCN PRNDKCCSGL KCGSNHNWCK LHI
