JZT34_CHIGU
ID JZT34_CHIGU Reviewed; 87 AA.
AC B1P1F7;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 25-MAY-2022, entry version 48.
DE RecName: Full=Mu-theraphotoxin-Cg1a {ECO:0000305};
DE Short=Mu-TRTX-Cg1a {ECO:0000305};
DE AltName: Full=Jingzhaotoxin-34 {ECO:0000303|PubMed:19463735, ECO:0000303|PubMed:29393892};
DE Short=JZTX-34 {ECO:0000303|PubMed:19463735, ECO:0000303|PubMed:29393892};
DE AltName: Full=Peptide F6-25.51 {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 [LARGE SCALE MRNA], AND FUNCTION.
RC TISSUE=Venom, and 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 [2]
RP PROTEIN SEQUENCE OF 51-62, MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
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.
RX PubMed=19463735; DOI=10.1016/j.peptides.2009.02.018;
RA Chen J., Zhang Y., Rong M., Zhao L., Jiang L., Zhang D., Wang M., Xiao Y.,
RA Liang S.;
RT "Expression and characterization of jingzhaotoxin-34, a novel neurotoxin
RT from the venom of the tarantula Chilobrachys jingzhao.";
RL Peptides 30:1042-1048(2009).
RN [4]
RP SYNTHESIS OF 51-85, AND FUNCTION.
RX PubMed=29393892; DOI=10.3390/toxins10020064;
RA Zeng X., Li P., Chen B., Huang J., Lai R., Liu J., Rong M.;
RT "Selective closed-state Nav1.7 blocker JZTX-34 exhibits analgesic effects
RT against pain.";
RL Toxins 10:1-13(2018).
CC -!- FUNCTION: Potent and selective inhibitor of hNav1.7/SCN9A (IC(50)=610
CC nM) (PubMed:29393892). Also shows a weak activity towards Nav1.3/SCN3A
CC (IC(50)=7950 nM) (PubMed:29393892). In addition, inhibits voltage-gated
CC potassium channels (Kv) in rat DRG neurons (PubMed:18581053). It does
CC not alter the voltage dependence of activation, but it causes a small
CC hyperpolarizing shift in the steady-state inactivations of Nav1.7/SNC9A
CC (PubMed:29393892). Chimera experiments show that the toxin binds to the
CC DIIS3-S4 linker (site 4) of Nav1.7/SCN9A, whereas Nav1.7/SCN9A Asp-827
CC residue is shown by substitution experiments to be critical for its
CC sensitivity (PubMed:19463735, PubMed:29393892). The toxin traps the
CC domain II voltage sensor in the closed configuration, and not in an
CC outward position (PubMed:29393892). In vivo, shows analgesic activity
CC in three rodent pain models (formalin-induced, acid-induced, and
CC thermal) (PubMed:29393892). {ECO:0000269|PubMed:18581053,
CC ECO:0000269|PubMed:29393892, ECO:0000305|PubMed:19463735}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17476710}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:17476710}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:B1P1E3}.
CC -!- MASS SPECTROMETRY: Mass=4153.5; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:17476710};
CC -!- PHARMACEUTICAL: Is a promising lead molecule for the development of
CC novel therapeutics in the treatment of pain.
CC {ECO:0000305|PubMed:29393892}.
CC -!- MISCELLANEOUS: Does not inhibit TTX-resistant sodium currents on rat
CC dorsal root ganglion (DRG) neurons (PubMed:18581053, PubMed:19463735,
CC PubMed:29393892). Has no activity on voltage-gated potassium channel
CC Kv2.1/KCNB1 expressed in frog oocytes (PubMed:19463735). Does not show
CC activity towards Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.4/SCN4A,
CC Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.8/SCN10A sodium channel
CC (PubMed:29393892). {ECO:0000269|PubMed:18581053,
CC ECO:0000269|PubMed:19463735, ECO:0000269|PubMed:29393892}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 39 (Jztx-34)
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 EMBL; EU233888; ABY71707.1; -; mRNA.
DR AlphaFoldDB; B1P1F7; -.
DR SMR; B1P1F7; -.
DR ArachnoServer; AS000836; mu-theraphotoxin-Cg1a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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; Pharmaceutical; Potassium channel impairing toxin; 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..50
FT /evidence="ECO:0000305|PubMed:17476710"
FT /id="PRO_0000379918"
FT PEPTIDE 51..85
FT /note="Mu-theraphotoxin-Cg1a"
FT /evidence="ECO:0000305|PubMed:17476710"
FT /id="PRO_0000379919"
FT DISULFID 52..66
FT /evidence="ECO:0000250|UniProtKB:B1P1E3"
FT DISULFID 59..71
FT /evidence="ECO:0000250|UniProtKB:B1P1E3"
FT DISULFID 65..79
FT /evidence="ECO:0000250|UniProtKB:B1P1E3"
SQ SEQUENCE 87 AA; 10136 MW; 24EB2AD5A4284B4C CRC64;
MKVLVLITLA VLGAMFVWTS AAELEERGSD QRDSPAWVKS MERIFQSEER ACREWLGGCS
KDADCCAHLE CRKKWPYHCV WDWTVRK
