JZT1A_CHIGU
ID JZT1A_CHIGU Reviewed; 62 AA.
AC P83974; Q5W1E3;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 25-MAY-2022, entry version 66.
DE RecName: Full=Delta-theraphotoxin-Cg1a 1 {ECO:0000305};
DE Short=Delta-TRTX-Cg1a {ECO:0000305};
DE AltName: Full=Jingzhaotoxin-1 {ECO:0000305};
DE AltName: Full=Jingzhaotoxin-I {ECO:0000303|PubMed:15548530};
DE Short=JZTX-I {ECO:0000303|PubMed:15548530};
DE AltName: Full=Peptide F5-24.92 {ECO:0000303|PubMed:17476710};
DE Flags: Precursor;
OS Chilobrachys guangxiensis (Chinese earth tiger tarantula) (Chilobrachys
OS jingzhao).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Chilobrachys.
OX NCBI_TaxID=278060;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-62, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15548530; DOI=10.1074/jbc.m411651200;
RA Xiao Y.-C., Tang J.Z., Hu W., Xie J.Y., Maertens C., Tytgat J., Liang S.P.;
RT "Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting
RT cardiac sodium channel inactivation.";
RL J. Biol. Chem. 280:12069-12076(2005).
RN [2]
RP PROTEIN SEQUENCE OF 30-62, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=17476710; DOI=10.1002/pmic.200600785;
RA Liao Z., Cao J., Li S., Yan X., Hu W., He Q., Chen J., Tang J., Xie J.,
RA Liang S.;
RT "Proteomic and peptidomic analysis of the venom from Chinese tarantula
RT Chilobrachys jingzhao.";
RL Proteomics 7:1892-1907(2007).
RN [3]
RP FUNCTION, AND BIOASSAY.
RC TISSUE=Venom;
RX PubMed=17150181; DOI=10.1016/j.bbrc.2006.11.086;
RA Yuan C., Yang S., Liao Z., Liang S.;
RT "Effects and mechanism of Chinese tarantula toxins on the Kv2.1 potassium
RT channels.";
RL Biochem. Biophys. Res. Commun. 352:799-804(2007).
RN [4]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=17618665; DOI=10.1016/j.toxicon.2007.04.018;
RA Xiao Y.-C., Li J., Deng M., Dai C.-L., Liang S.-P.;
RT "Characterization of the excitatory mechanism induced by Jingzhaotoxin-I
RT inhibiting sodium channel inactivation.";
RL Toxicon 50:507-517(2007).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=23246579; DOI=10.1016/j.toxicon.2012.12.001;
RA Tao H., Wu Y., Deng M., He J., Wang M., Xiao Y., Liang S.;
RT "Molecular determinants for the tarantula toxin jingzhaotoxin-I interacting
RT with potassium channel Kv2.1.";
RL Toxicon 63:129-136(2013).
RN [6]
RP FUNCTION.
RX PubMed=26721415; DOI=10.1016/j.toxicon.2015.12.009;
RA Tao H., Chen X., Lu M., Wu Y., Deng M., Zeng X., Liu Z., Liang S.;
RT "Molecular determinant for the tarantula toxin Jingzhaotoxin-I slowing the
RT fast inactivation of voltage-gated sodium channels.";
RL Toxicon 111:13-21(2016).
RN [7]
RP STRUCTURE BY NMR OF 30-62, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=16077905; DOI=10.1111/j.1745-7270.2005.00078.x;
RA Zeng X.-Z., Zhu Q., Liang S.-P.;
RT "Sequence-specific assignment of 1H-NMR resonance and determination of the
RT secondary structure of Jingzhaotoxin-I.";
RL Acta Biochim. Biophys. Sin. 37:567-572(2005).
CC -!- FUNCTION: Inhibits voltage-gated sodium channels, preferentially
CC subtype Nav1.5/SCN5A (in cardiac myocytes), but also Nav1.6/SCN8A and
CC Nav1.7/SCN9A (TTX-sensitive Nav in rat DRG neurons) and invertebrate
CC Nav (in insect neurons) as well as voltage-gated potassium channels of
CC the subtype Kv2.1/KCNB1. Is suggested to bind to site 3 of the sodium
CC channels and inhibit the inactivation of the activated channels,
CC thereby blocking neuronal transmission. On potassium channels, inhibits
CC activation of channels with an IC(50) of 8.05 uM through a voltage
CC sensor-trapping mechanism (PubMed:23246579). Increases muscle
CC contraction in several assays (mouse phrenic nerve-diaphragm, toad
CC heart, rat vas deferens) and is suggested to act both presynaptically
CC and postsynaptically. {ECO:0000269|PubMed:15548530,
CC ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17618665,
CC ECO:0000269|PubMed:23246579}.
CC -!- FUNCTION: Moderately inhibits voltage-gated sodium channels and weakly
CC inhibits voltage-gated potassium channel (PubMed:17150181,
CC PubMed:17618665, PubMed:23246579, PubMed:26721415). Inhibits the
CC inactivation of rat Nav1.2/SCN2A (IC(50)=870 nM), rat Nav1.3/SCN3A
CC (IC(50)=845 nM), rat Nav1.4/SCN4A (IC(50)=339 nM), human Nav1.5/SCN5A
CC (IC(50)=335 nM) and human Nav1.7/SCN9A sodium channels (IC(50)=348 nM)
CC (PubMed:26721415). The toxin delays the inactivation of sodium channels
CC without affecting the activation and steady-state inactivation kinetics
CC in the physiological range of voltages (PubMed:26721415). Site-directed
CC mutagenesis of the sodium channel indicates that the toxin interacts
CC with site 3 located at the extracellular S3-S4 linker of domain IV
CC (PubMed:26721415). On potassium channels, it inhibits activation of
CC channels with an IC(50) of 8.05 uM through a voltage sensor-trapping
CC mechanism (PubMed:23246579). It increases muscle contraction in several
CC assays (mouse phrenic nerve-diaphragm, toad heart, rat vas deferens)
CC and is suggested to act both presynaptically and postsynaptically
CC (PubMed:17618665). {ECO:0000269|PubMed:15548530,
CC ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17618665,
CC ECO:0000269|PubMed:23246579, ECO:0000269|PubMed:26721415}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15548530}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15548530}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:16077905}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 33 (Jztx-1)
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ854060; CAH69598.1; -; mRNA.
DR AlphaFoldDB; P83974; -.
DR SMR; P83974; -.
DR ArachnoServer; AS000045; delta-theraphotoxin-Cg1a.
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:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
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 Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Postsynaptic neurotoxin;
KW Potassium channel impairing toxin; Presynaptic neurotoxin; Secreted;
KW Signal; Toxin; Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..29
FT /evidence="ECO:0000269|PubMed:15548530,
FT ECO:0000269|PubMed:17476710"
FT /id="PRO_0000398385"
FT CHAIN 30..62
FT /note="Delta-theraphotoxin-Cg1a 1"
FT /evidence="ECO:0000269|PubMed:15548530,
FT ECO:0000269|PubMed:17476710"
FT /id="PRO_0000035594"
FT DISULFID 31..46
FT /evidence="ECO:0000269|PubMed:16077905"
FT DISULFID 38..51
FT /evidence="ECO:0000269|PubMed:16077905"
FT DISULFID 45..58
FT /evidence="ECO:0000269|PubMed:16077905"
SQ SEQUENCE 62 AA; 6894 MW; 6B2307268A528176 CRC64;
MKTSILFVIF SLALLFALSA ATEIEETDRA CGQFWWKCGE GKPPCCANFA CKIGLYLCIW
SP
