JZTX5_CHIGU
ID JZTX5_CHIGU Reviewed; 83 AA.
AC Q2PAY4; P84629;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Beta/kappa-theraphotoxin-Cg2a {ECO:0000303|PubMed:29723257};
DE Short=Beta/kappa-TRTX-Cg2a {ECO:0000303|PubMed:29723257};
DE AltName: Full=Beta-theraphotoxin-Cj2a {ECO:0000303|PubMed:25055801};
DE AltName: Full=Jingzhaotoxin-5 {ECO:0000305};
DE AltName: Full=Jingzhaotoxin-V {ECO:0000303|PubMed:17150181, ECO:0000303|PubMed:17157888, ECO:0000303|PubMed:20571743};
DE Short=JZTX-V {ECO:0000303|PubMed:17150181, ECO:0000303|PubMed:17157888, ECO:0000303|PubMed:18581053, ECO:0000303|PubMed:20571743};
DE AltName: Full=Peptide F8-15.73;
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 54-82, FUNCTION,
RP SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND AMIDATION AT ILE-82.
RC TISSUE=Venom, and Venom gland;
RX PubMed=17157888; DOI=10.1016/j.toxicon.2006.10.012;
RA Zeng X.Z., Deng M., Lin Y., Yuan C., Pi J., Liang S.-P.;
RT "Isolation and characterization of Jingzhaotoxin-V, a novel neurotoxin from
RT the venom of the spider Chilobrachys jingzhao.";
RL Toxicon 49:388-399(2007).
RN [2]
RP PROTEIN SEQUENCE OF 54-82, 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 SYNTHESIS OF 54-82, AND FUNCTION.
RX PubMed=20571743;
RA Cai L.-J., Xu D.-H., Luo J., Chen R.-Z., Chi Y.-P., Zeng X.Z., Wang X.-C.,
RA Liang S.-P.;
RT "Inhibition of Jingzhaotoxin-V on Kv4.3 channel.";
RL Sheng Li Xue Bao 62:255-260(2010).
RN [4]
RP FUNCTION.
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 [5]
RP FUNCTION.
RC TISSUE=Venom gland;
RX PubMed=18581053; DOI=10.1007/s00018-008-8135-x;
RA Chen J., Deng M., He Q., Meng E., Jiang L., Liao Z., Rong M., Liang S.;
RT "Molecular diversity and evolution of cystine knot toxins of the tarantula
RT Chilobrachys jingzhao.";
RL Cell. Mol. Life Sci. 65:2431-2444(2008).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF TRP-58; MET-59; TRP-60; ARG-73 AND LYS-75.
RX PubMed=25055801; DOI=10.3390/toxins6072177;
RA Luo J., Zhang Y., Gong M., Lu S., Ma Y., Zeng X., Liang S.;
RT "Molecular surface of JZTX-V (beta-Theraphotoxin-Cj2a) interacting with
RT voltage-gated sodium channel subtype NaV1.4.";
RL Toxins 6:2177-2193(2014).
RN [7]
RP STRUCTURE BY NMR OF 54-82 OF MUTANTS PRA-[NLE6]JZTX-V(1-29) AND AM-8145,
RP DISULFIDE BOND, FUNCTION, FUNCTION OF ANALOGS AM-8145; AM-0422 AND AM-8394,
RP AND SYNTHESIS OF 54-82.
RC TISSUE=Venom;
RX PubMed=29723257; DOI=10.1371/journal.pone.0196791;
RA Moyer B.D., Murray J.K., Ligutti J., Andrews K., Favreau P., Jordan J.B.,
RA Lee J.H., Liu D., Long J., Sham K., Shi L., Stoecklin R., Wu B., Yin R.,
RA Yu V., Zou A., Biswas K., Miranda L.P.;
RT "Pharmacological characterization of potent and selective NaV1.7 inhibitors
RT engineered from Chilobrachys jingzhao tarantula venom peptide JzTx-V.";
RL PLoS ONE 13:E0196791-E0196791(2018).
CC -!- FUNCTION: This gating-modifier toxin shows an important inhibitory
CC activity on sodium channels (PubMed:29723257). It is very active on
CC Nav1.7/SCN9A (IC(50)~0.6 nM), and also shows activity on Nav1.3/SCN3A
CC (IC(50)=292 nM), Nav1.4/SCN4A (IC(50)=2.2-159 nM), and Nav1.5/SCN5A
CC (IC(50)=2.3-2.9 uM) (PubMed:25055801, PubMed:29723257). It has also
CC been shown to inhibit tetrodotoxin (TTX)-resistant (IC(50)=27.6 nM) and
CC TTX-sensitive (IC(50)=30.2 nM) sodium channels in rat dorsal root
CC ganglion neurons (PubMed:17157888). Lower inhibitory activity has also
CC been shown on potassium channels: Kv4.2/KCND2 (IC(50)=604.2 nM),
CC Kv4.3/KCND3 (IC(50)=425.1 nM), and Kv2.1/KCNB1 (IC(50)=14.3 uM)
CC (PubMed:17157888, PubMed:20571743, PubMed:17150181). It binds to
CC phospholipid membranes. Like its analog AM-8145, it may act by
CC interacting only with the second voltage-sensor domain of Nav1.7/SCN9A
CC (Probable). {ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17157888,
CC ECO:0000269|PubMed:18581053, ECO:0000269|PubMed:20571743,
CC ECO:0000269|PubMed:29723257}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17157888}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:17157888}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:29723257}.
CC -!- MASS SPECTROMETRY: Mass=3605.73; Mass_error=0.3; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17157888};
CC -!- MISCELLANEOUS: Does not inhibit Kv1.2/KCNA2, Kv1.3/KCNA3, and
CC Kv1.4/KCNA4 channels (PubMed:17157888). Shows an extremely weak
CC inhibition on Kv4.1/KCND1 (PubMed:17150181).
CC {ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17157888}.
CC -!- MISCELLANEOUS: The analog AM-8145 has a propargylglycine (Pra) N-
CC terminally inserted, a norleucine (Nle) that replaces Met-59 (Met-6),
CC and a Glu instead of Ile-81 (Ile-28). This analog potently blocks
CC Nav1.7/SCN9A (IC(50)=0.5 nM) by interacting only with its second
CC voltage-sensor domain (PubMed:29723257). It is 30- to 120-fold less
CC active on TTX-sensitive sodium channels, and shows no or very low
CC activity on TTX-resistant sodium channels (PubMed:29723257).
CC {ECO:0000269|PubMed:29723257}.
CC -!- MISCELLANEOUS: The analog AM-0422 has a beta-cyanoalanine (CyA) N-
CC terminally inserted, a norleucine (Nle) that replaces Met-59 (Met-6), a
CC propargylglycine (Pra) instead of Glu-70 (Glu-17), and a Glu instead of
CC Ile-81 (Ile-28). This analog potently blocks Nav1.7/SCN9A (IC(50)=0.8
CC nM) (PubMed:29723257). It also potently blocks TTX-sensitive sodium
CC channels in mouse and rat DRG neurons (IC(50)=9-27 nM)
CC (PubMed:29723257). It also specifically blocks capsaicin-induced rat
CC DRG neuron action potential firing (PubMed:29723257). In addition, it
CC specifically blocks mechanically-induced C-fiber action potential
CC firing from afferent nerve terminals (PubMed:29723257).
CC {ECO:0000269|PubMed:29723257}.
CC -!- MISCELLANEOUS: The analog AM-8394 has a propargylglycine (Pra) N-
CC terminally inserted, a norleucine (Nle) that replaces Met-59 (Met-6),
CC and Glu residues instead of Leu-72 (Leu-19) and Ile-81 (Ile-28)
CC (PubMed:29723257). This analog show a weak inhibitory activity on
CC Nav1.7/SCN9A (IC(50)>1 uM) (PubMed:29723257). It does not show activity
CC on TTX-sensitive sodium channels in mouse and rat DRG neurons
CC (PubMed:29723257). As a consequence, it can be used as a negative
CC control peptide. {ECO:0000269|PubMed:29723257}.
CC -!- SIMILARITY: Belongs to the neurotoxin 30 (phrixotoxin) family.
CC {ECO:0000305}.
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DR EMBL; AM072411; CAJ21615.1; -; mRNA.
DR PDB; 6CGW; NMR; -; A=54-82.
DR PDB; 6CHC; NMR; -; A=53-82.
DR PDB; 6CNU; X-ray; 1.05 A; B=55-82.
DR PDBsum; 6CGW; -.
DR PDBsum; 6CHC; -.
DR PDBsum; 6CNU; -.
DR AlphaFoldDB; Q2PAY4; -.
DR SMR; Q2PAY4; -.
DR PRIDE; Q2PAY4; -.
DR ArachnoServer; AS000047; beta/kappa-theraphotoxin-Cg2a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..53
FT /evidence="ECO:0000305|PubMed:17157888,
FT ECO:0000305|PubMed:17476710"
FT /id="PRO_0000262454"
FT PEPTIDE 54..82
FT /note="Beta/kappa-theraphotoxin-Cg2a"
FT /evidence="ECO:0000269|PubMed:17157888,
FT ECO:0000269|PubMed:17476710"
FT /id="PRO_0000262455"
FT MOD_RES 82
FT /note="Isoleucine amide"
FT /evidence="ECO:0000269|PubMed:17157888"
FT DISULFID 55..69
FT /evidence="ECO:0000269|PubMed:29723257,
FT ECO:0000312|PDB:6CGW, ECO:0000312|PDB:6CHC"
FT DISULFID 62..74
FT /evidence="ECO:0000269|PubMed:29723257,
FT ECO:0000312|PDB:6CGW, ECO:0000312|PDB:6CHC"
FT DISULFID 68..78
FT /evidence="ECO:0000269|PubMed:29723257,
FT ECO:0000312|PDB:6CGW, ECO:0000312|PDB:6CHC"
FT MUTAGEN 58
FT /note="W->A: 61-fold decrease of binding affinity to
FT Nav1.4/SCN4A."
FT /evidence="ECO:0000269|PubMed:25055801"
FT MUTAGEN 59
FT /note="M->A: 49-fold decrease of binding affinity to
FT Nav1.4/SCN4A."
FT /evidence="ECO:0000269|PubMed:25055801"
FT MUTAGEN 60
FT /note="W->A: 375-fold decrease of binding affinity to
FT Nav1.4/SCN4A."
FT /evidence="ECO:0000269|PubMed:25055801"
FT MUTAGEN 73
FT /note="R->A: 410-fold decrease of binding affinity to
FT Nav1.4/SCN4A."
FT /evidence="ECO:0000269|PubMed:25055801"
FT MUTAGEN 75
FT /note="K->A: 128-fold decrease of binding affinity to
FT Nav1.4/SCN4A."
FT /evidence="ECO:0000269|PubMed:25055801"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:6CGW"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:6CHC"
FT STRAND 72..80
FT /evidence="ECO:0007829|PDB:6CNU"
SQ SEQUENCE 83 AA; 9586 MW; E3DEDBD88AB3AACC CRC64;
MKASVFAVIL GLVVLCACSF AEDEQDQFVS PNELLKSMFV ESRHEFTPEV EGRYCQKWMW
TCDSKRACCE GLRCKLWCRK IIG
