TXNA1_OMOSC
ID TXNA1_OMOSC Reviewed; 33 AA.
AC A0A4V8GZX0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 2.
DT 25-MAY-2022, entry version 12.
DE RecName: Full=Mu-theraphotoxin-Os1a {ECO:0000305};
DE Short=Mu-TRTX-Os1a {ECO:0000305};
DE AltName: Full=Cyriotoxin-1a {ECO:0000303|PubMed:30784059};
DE Short=CyrTx-1a {ECO:0000303|PubMed:30784059};
DE AltName: Full=Mu-theraphotoxin-Cs1a {ECO:0000303|PubMed:30784059};
OS Omothymus schioedtei (Malaysian earth tiger tarantula) (Cyriopagopus
OS schioedtei).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Cyriopagopus.
OX NCBI_TaxID=1046902;
RN [1] {ECO:0000312|PDB:6GFT, ECO:0007744|PDB:6GFT}
RP PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, SYNTHESIS, STRUCTURE BY NMR,
RP DISULFIDE BONDS, AMIDATION AT LEU-33, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=30784059; DOI=10.1111/bph.14628;
RA Goncalves T.C., Benoit E., Kurz M., Lucarain L., Fouconnier S.,
RA Combemale S., Jaquillard L., Schombert B., Chambard J.M., Boukaiba R.,
RA Hessler G., Bohme A., Bialy L., Hourcade S., Beroud R., De Waard M.,
RA Servent D., Partiseti M.;
RT "From identification to functional characterization of cyriotoxin-1a, an
RT antinociceptive toxin from the spider Cyriopagopus schioedtei.";
RL Br. J. Pharmacol. 176:1298-1314(2019).
CC -!- FUNCTION: Potently and reversibly inhibits some human voltage-gated
CC sodium channels (Nav1.1/SCN1A (IC(50)=72.0 nM), Nav1.2/SCN2A
CC (IC(50)=75.5 nM), Nav1.6/SCN8A (IC(50)=115.0 nM), Nav1.7/SCN9A
CC (IC(50)=52.7-129.5 nM), Nav1.3/SCN3A (IC(50)=306.6 nM))
CC (PubMed:30784059). The hNav1.7/SCN9A channel inhibition occurs without
CC any change in steady-state inactivation- and conductance-voltage
CC relationships (PubMed:30784059). On adult mouse DRG neurons, this toxin
CC is approximately 1000-fold more efficient to inhibit tetrodotoxin
CC (TTX)-sensitive than TTX-resistant sodium currents (PubMed:30784059).
CC In vivo, this toxin exhibits analgesic effects in mice pain models
CC (PubMed:30784059). {ECO:0000269|PubMed:30784059}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:D2Y1X8}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30784059}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:30784059}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:30784059}.
CC -!- MASS SPECTROMETRY: Mass=3578.68; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:30784059};
CC -!- TOXIC DOSE: LD(50) is 144.4 nmol/kg by intramuscular injection within 1
CC hr. {ECO:0000269|PubMed:30784059}.
CC -!- MISCELLANEOUS: Shows low or no activity on hNav1.4/SCN4A (IC(50)=7.7
CC uM), hNav1.5/SCN5A (IC(50)>10 uM), hNav1.8/SCN10A (IC(50)>10 uM),
CC hCav1.2/CACNA1C, hCav3.1/CACNA1G, hCav3.2CACNA1H, hKv7.1/KCNQ1,
CC Kv11.1/KCNH2/ERG1, and hKir2.1/KCNJ2/IRK1 channels.
CC {ECO:0000269|PubMed:30784059}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 14 (Hntx-1)
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR PDB; 6GFT; NMR; -; A=1-33.
DR PDBsum; 6GFT; -.
DR AlphaFoldDB; A0A4V8GZX0; -.
DR BMRB; A0A4V8GZX0; -.
DR SMR; A0A4V8GZX0; -.
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 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; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..33
FT /note="Mu-theraphotoxin-Os1a"
FT /evidence="ECO:0000269|PubMed:30784059"
FT /id="PRO_0000452541"
FT MOD_RES 33
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:30784059"
FT DISULFID 2..17
FT /evidence="ECO:0000269|PubMed:30784059,
FT ECO:0007744|PDB:6GFT"
FT DISULFID 9..22
FT /evidence="ECO:0000269|PubMed:30784059,
FT ECO:0007744|PDB:6GFT"
FT DISULFID 16..29
FT /evidence="ECO:0000269|PubMed:30784059,
FT ECO:0007744|PDB:6GFT"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:6GFT"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:6GFT"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:6GFT"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:6GFT"
SQ SEQUENCE 33 AA; 3588 MW; 57CFD62C2A50E27C CRC64;
ECKGFGKSCV PGKNECCSGL TCSNKHKWCK VLL
