TXH1_CYRSC
ID TXH1_CYRSC Reviewed; 81 AA.
AC P56676; Q86C48; Q9NJC2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2003, sequence version 2.
DT 25-MAY-2022, entry version 101.
DE RecName: Full=Mu/omega-theraphotoxin-Hs1a {ECO:0000303|PubMed:31234412};
DE Short=Mu/omega-TRTX-Hs1a {ECO:0000303|PubMed:31234412};
DE AltName: Full=Huwentoxin-1 {ECO:0000305};
DE Short=HwTx-1 {ECO:0000305};
DE AltName: Full=Huwentoxin-I {ECO:0000303|PubMed:8136023, ECO:0000303|PubMed:8212049};
DE Short=HwTx-I {ECO:0000303|PubMed:8136023, ECO:0000303|PubMed:8212049};
DE Flags: Precursor;
OS Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Cyriopagopus.
OX NCBI_TaxID=29017;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=14757201; DOI=10.1016/j.toxicon.2003.08.007;
RA Diao J., Lin Y., Tang J., Liang S.-P.;
RT "cDNA sequence analysis of seven peptide toxins from the spider
RT Selenocosmia huwena.";
RL Toxicon 42:715-723(2003).
RN [2]
RP PROTEIN SEQUENCE OF 49-81, FUNCTION, SUBCELLULAR LOCATION, AND LETHAL
RP DOSES.
RC TISSUE=Venom;
RX PubMed=8212049; DOI=10.1016/0041-0101(93)90256-i;
RA Liang S.-P., Zhang D.-Y., Pan X., Chen Q., Zhou P.-A.;
RT "Properties and amino acid sequence of huwentoxin-I, a neurotoxin purified
RT from the venom of the Chinese bird spider Selenocosmia huwena.";
RL Toxicon 31:969-978(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 49-80.
RC TISSUE=Venom gland;
RA Li M., Zhou Z., Liang S.-P.;
RT "Sequence and cloning of huwentoxin-I cDNA.";
RL Zhongguo Sheng Wu Hua Xue Yu Fen Zi Sheng Wu Xue Bao 17:51-55(2001).
RN [4]
RP DISULFIDE BONDS, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8136023; DOI=10.1007/bf01024931;
RA Zhang D.-Y., Liang S.-P.;
RT "Assignment of the three disulfide bridges of huwentoxin-I, a neurotoxin
RT from the spider Selenocosmia huwena.";
RL J. Protein Chem. 12:735-740(1993).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=9028007; DOI=10.1016/s0041-0101(96)00072-4;
RA Zhou P.-A., Xie X.-J., Li M., Yang D.-M., Xie Z.-P., Zong X., Liang S.-P.;
RT "Blockade of neuromuscular transmission by huwentoxin-I, purified from the
RT venom of the Chinese bird spider Selenocosmia huwena.";
RL Toxicon 35:39-45(1997).
RN [6]
RP MUTAGENESIS OF LYS-51.
RA Wang X.-C., Liang S.-P., Luo Z.-M.;
RT "Chemical synthesis and physiological analysis of K3A-HWTX-I: a mutant of
RT huwentoxin-I.";
RL Sheng Ming Ke Xue Yan Jiu 2:87-92(1998).
RN [7]
RP MUTAGENESIS OF ARG-68.
RX PubMed=11051826;
RA Wang X.-C., Liang S.-P., Luo Z.-M.;
RT "Chemical synthesis and characterization of R20A-HWTX-I, a mutant of
RT huwentoxin-I with single residue replacement.";
RL Sheng Wu Gong Cheng Xue Bao 16:490-494(2000).
RN [8]
RP FUNCTION.
RX PubMed=10736477; DOI=10.1016/s0041-0101(99)00224-x;
RA Liang S.-P., Chen X.-D., Shu Q., Zhang Y., Peng K.;
RT "The presynaptic activity of huwentoxin-I, a neurotoxin from the venom of
RT the Chinese bird spider Selenocosmia huwena.";
RL Toxicon 38:1237-1246(2000).
RN [9]
RP MUTAGENESIS OF ALA-49.
RA Wang X.-C., Liang S.-P., Luo Z.-M.;
RT "Solid-phase synthesis and bioactivity analysis of A1Y-HWTX-I: a mutant of
RT huwentoxin-I.";
RL Zhongguo Sheng Wu Hua Xue Yu Fen Zi Sheng Wu Xue Bao 16:357-362(2000).
RN [10]
RP FUNCTION.
RX PubMed=11024489; DOI=10.1016/s0041-0101(00)00150-1;
RA Peng K., Chen X.D., Liang S.-P.;
RT "The effect of huwentoxin-I on Ca(2+) channels in differentiated NG108-15
RT cells, a patch-clamp study.";
RL Toxicon 39:491-498(2001).
RN [11]
RP FUNCTION, AND BIOASSAY IN PAIN MODEL.
RX PubMed=15581678; DOI=10.1016/j.toxicon.2004.08.018;
RA Chen J.Q., Zhang Y.Q., Dai J., Luo Z.M., Liang S.P.;
RT "Antinociceptive effects of intrathecally administered huwentoxin-I, a
RT selective N-type calcium channel blocker, in the formalin test in conscious
RT rats.";
RL Toxicon 45:15-20(2005).
RN [12]
RP FUNCTION.
RX PubMed=17451655; DOI=10.1016/j.bbrc.2007.02.168;
RA Wang M., Guan X., Liang S.;
RT "The cross channel activities of spider neurotoxin huwentoxin-I on rat
RT dorsal root ganglion neurons.";
RL Biochem. Biophys. Res. Commun. 357:579-583(2007).
RN [13]
RP FUNCTION, AND RECOMBINANT EXPRESSION.
RX PubMed=21731778; DOI=10.1371/journal.pone.0021608;
RA Meng E., Cai T.F., Li W.Y., Zhang H., Liu Y.B., Peng K., Liang S.,
RA Zhang D.Y.;
RT "Functional expression of spider neurotoxic peptide huwentoxin-I in E.
RT coli.";
RL PLoS ONE 6:e21608-e21608(2011).
RN [14]
RP FUNCTION ON NAV1.7/SCN9A, AND SYNTHESIS OF 49-81.
RX PubMed=31234412; DOI=10.3390/toxins11060367;
RA Nicolas S., Zoukimian C., Bosmans F., Montnach J., Diochot S., Cuypers E.,
RA De Waard S., Beroud R., Mebs D., Craik D., Boturyn D., Lazdunski M.,
RA Tytgat J., De Waard M.;
RT "Chemical synthesis, proper folding, Nav channel selectivity profile and
RT analgesic properties of the spider peptide Phlotoxin 1.";
RL Toxins 11:0-0(2019).
RN [15]
RP STRUCTURE BY NMR OF 49-81, AND DISULFIDE BOND.
RC TISSUE=Venom;
RX PubMed=9263120; DOI=10.1023/a:1026314722607;
RA Qu Y.-X., Liang S.-P., Ding J., Liu X.-C., Zhang R.-J., Gu X.-C.;
RT "Proton nuclear magnetic resonance studies on huwentoxin-I from the venom
RT of the spider Selenocosmia huwena: 2. Three-dimensional structure in
RT solution.";
RL J. Protein Chem. 16:565-574(1997).
CC -!- FUNCTION: Lethal toxin with multiple biological activities. Inhibits
CC voltage-gated TTX-sensitive sodium channels in DRG neurons (IC(50)=55
CC nM) and also shows activity when directly tested on Nav1.7/SCN9A
CC (IC(50)=25.1-630 nM) (PubMed:17451655, PubMed:21731778,
CC PubMed:31234412). Inhibits N-type calcium channels (Cav2.2/CACNA1B
CC (IC(50)=100 nM)) (PubMed:11024489, PubMed:17451655). Also blocks
CC neuromuscular transmission (PubMed:8212049, PubMed:9028007,
CC PubMed:10736477). In vivo, intrathecal injected toxin shows analgesic
CC activity in the rat formalin-induced pain model, without induction of
CC motor dysfunction in rats. {ECO:0000269|PubMed:15581678}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8136023,
CC ECO:0000269|Ref.3}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8136023, ECO:0000305|Ref.3}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:8136023, ECO:0000269|PubMed:9263120}.
CC -!- TOXIC DOSE: LD(50) is 0.7 mg/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:8212049}.
CC -!- TOXIC DOSE: LD(50) is 9.40 ug/kg by intracisternal injection into mice.
CC {ECO:0000269|PubMed:8212049}.
CC -!- MISCELLANEOUS: Shows very weak effect on calcium channel Cav1 subtypes
CC (PubMed:11024489, PubMed:17451655). Does not show effect on calcium
CC channel Cav3 subtypes (PubMed:11024489, PubMed:17451655). Does not show
CC effect on voltage-gated potassium channels Kv (delayed rectifier)
CC (PubMed:11024489). Does not show effect on voltage-gated TTX-resistant
CC sodium channels (PubMed:17451655). {ECO:0000269|PubMed:11024489,
CC ECO:0000269|PubMed:17451655}.
CC -!- MISCELLANEOUS: Is the most abundant toxin in the crude venom.
CC {ECO:0000305|PubMed:21731778}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 23 (HwTx-I)
CC subfamily. {ECO:0000305}.
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DR EMBL; AY263711; AAP33078.1; -; mRNA.
DR EMBL; AF157504; AAF25774.1; -; mRNA.
DR PIR; A37479; A37479.
DR PDB; 1QK6; NMR; -; A=49-81.
DR PDBsum; 1QK6; -.
DR AlphaFoldDB; P56676; -.
DR SMR; P56676; -.
DR TCDB; 8.B.3.1.1; the huwentoxin-1 (huwentoxin-1) family.
DR ArachnoServer; AS000327; mu/omega-theraphotoxin-Hs1a.
DR EvolutionaryTrace; P56676; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
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; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW Postsynaptic neurotoxin; Presynaptic neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..48
FT /evidence="ECO:0000305|PubMed:8212049"
FT /id="PRO_0000035558"
FT CHAIN 49..81
FT /note="Mu/omega-theraphotoxin-Hs1a"
FT /evidence="ECO:0000269|PubMed:8212049"
FT /id="PRO_0000035559"
FT DISULFID 50..65
FT /evidence="ECO:0000269|PubMed:8136023,
FT ECO:0000269|PubMed:9263120, ECO:0000312|PDB:1QK6"
FT DISULFID 57..70
FT /evidence="ECO:0000269|PubMed:8136023,
FT ECO:0000269|PubMed:9263120, ECO:0000312|PDB:1QK6"
FT DISULFID 64..77
FT /evidence="ECO:0000269|PubMed:8136023,
FT ECO:0000269|PubMed:9263120, ECO:0000312|PDB:1QK6"
FT MUTAGEN 49
FT /note="A->Y: No decrease in bioactivity."
FT /evidence="ECO:0000269|Ref.9"
FT MUTAGEN 51
FT /note="K->A: Decrease in bioactivity."
FT /evidence="ECO:0000269|Ref.6"
FT MUTAGEN 68
FT /note="R->A: 92% decrease in bioactivity."
FT /evidence="ECO:0000269|PubMed:11051826"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:1QK6"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:1QK6"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1QK6"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:1QK6"
SQ SEQUENCE 81 AA; 9319 MW; AB45FB6FEE7C8BF3 CRC64;
MRASMFLALA GLVLLFVVCY ASESEEKEFP RELLFKFFAV DDFKGEERAC KGVFDACTPG
KNECCPNRVC SDKHKWCKWK L
