JZ11A_CHIGU
ID JZ11A_CHIGU Reviewed; 86 AA.
AC P0C247;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 25-MAY-2022, entry version 60.
DE RecName: Full=Kappa-theraphotoxin-Cg1a 1 {ECO:0000303|PubMed:25240294};
DE Short=Kappa-TRTX-Cg1a {ECO:0000303|PubMed:25240294};
DE AltName: Full=Jingzhaotoxin-11;
DE Short=JZTX-11;
DE AltName: Full=Jingzhaotoxin-XI {ECO:0000303|PubMed:17176080};
DE Short=JZTX-XI {ECO:0000303|PubMed:17176080};
DE AltName: Full=Peptide F4-13.64 {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 51-84, SUBCELLULAR
RP LOCATION, FUNCTION, MASS SPECTROMETRY, STRUCTURE BY NMR OF 51-84, AMIDATION
RP AT PHE-84, AND DISULFIDE BONDS.
RC TISSUE=Venom, and Venom gland;
RX PubMed=17176080; DOI=10.1021/bi061457+;
RA Liao Z., Yuan C., Deng M., Li J., Chen J., Yang Y., Hu W., Liang S.;
RT "Solution structure and functional characterization of Jingzhaotoxin-XI: a
RT novel gating modifier of both potassium and sodium channels.";
RL Biochemistry 45:15591-15600(2006).
RN [2]
RP PROTEIN SEQUENCE OF 51-84, 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 PROTEIN SEQUENCE OF 51-84, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=25240294; DOI=10.1016/j.toxicon.2014.09.002;
RA Tang C., Zhou X., Huang Y., Zhang Y., Hu Z., Wang M., Chen P., Liu Z.,
RA Liang S.;
RT "The tarantula toxin jingzhaotoxin-XI (kappa-theraphotoxin-Cj1a) regulates
RT the activation and inactivation of the voltage-gated sodium channel
RT Nav1.5.";
RL Toxicon 92:6-13(2014).
CC -!- FUNCTION: This toxin acts as a voltage-dependent gating-modifier
CC (PubMed:25240294). It inhibits the sodium conductance (IC(50)=124 nM)
CC and slows the fast inactivation (EC(50)=1180 nM) of Nav1.5/SCN5A
CC (PubMed:17176080, PubMed:25240294). It significantly shifts the
CC activation to more depolarized voltages and decreases the deactivation
CC of Nav1.5 currents upon extreme depolarization, but only slightly
CC affects voltage-dependence of steady-state inactivation
CC (PubMed:17176080, PubMed:25240294). In addition, this toxin causes an
CC approximately five-fold decrease in the rate of recovery from
CC inactivation and an approximately 1.9-fold reduction in the closed-
CC state inactivation rate (PubMed:25240294). This toxin integrates the
CC functions of site 3 toxins (alpha-scorpion toxins) with site 4 toxins
CC (beta-scorpion and spider toxins) by targeting multiple sites on Nav1.5
CC (PubMed:25240294). Also shows inhibition of voltage-gated potassium
CC channels (5 uM completely inhibits Kv2.1/KCNB1, whereas 5 uM moderately
CC inhibits Kv4.2/KCND2 Kv4.1/KCND1 channels) (PubMed:17176080).
CC {ECO:0000269|PubMed:17176080, ECO:0000269|PubMed:25240294}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17176080,
CC ECO:0000269|PubMed:17476710, ECO:0000269|PubMed:25240294}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:17176080, ECO:0000305|PubMed:17476710}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:17176080}.
CC -!- MASS SPECTROMETRY: Mass=3726.38; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17176080};
CC -!- MISCELLANEOUS: This toxin does not show effect on Kv1.1/KCNA1,
CC Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, Kv3.1/KCNC1 (all expressed in
CC oocytes), voltage-gated sodium channels (Nav1/SCN) (from DRG neurons),
CC and in a range of voltage-gated calcium channels (expressed in rat DRG
CC neurons) (PubMed:17176080). Does not show significant toxic symptoms
CC when injected into mice and into cockroaches (PubMed:17176080).
CC {ECO:0000305|PubMed:17176080}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 28 (Jztx-11)
CC subfamily. {ECO:0000305}.
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DR PDB; 2A2V; NMR; -; A=51-84.
DR PDBsum; 2A2V; -.
DR AlphaFoldDB; P0C247; -.
DR SMR; P0C247; -.
DR TCDB; 8.B.5.3.5; the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.
DR ArachnoServer; AS000043; kappa-theraphotoxin-Cg1a.
DR EvolutionaryTrace; P0C247; -.
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 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..50
FT /evidence="ECO:0000269|PubMed:17176080,
FT ECO:0000269|PubMed:17476710"
FT /id="PRO_0000287431"
FT PEPTIDE 51..84
FT /note="Kappa-theraphotoxin-Cg1a 1"
FT /evidence="ECO:0000269|PubMed:17176080,
FT ECO:0000269|PubMed:17476710, ECO:0000269|PubMed:25240294"
FT /id="PRO_0000262456"
FT REGION 55..56
FT /note="Involved in active face"
FT /evidence="ECO:0000250"
FT SITE 80
FT /note="Involved in active face"
FT /evidence="ECO:0000250"
FT MOD_RES 84
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:17176080"
FT DISULFID 52..66
FT /evidence="ECO:0000269|PubMed:17176080,
FT ECO:0007744|PDB:2A2V"
FT DISULFID 59..71
FT /evidence="ECO:0000269|PubMed:17176080,
FT ECO:0007744|PDB:2A2V"
FT DISULFID 65..78
FT /evidence="ECO:0000269|PubMed:17176080,
FT ECO:0007744|PDB:2A2V"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:2A2V"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:2A2V"
SQ SEQUENCE 86 AA; 9527 MW; FD137D8FD06B9AD9 CRC64;
MKVSVLITLA VLGVMFVWAS AAELEERGSD QRDSPAWLKS MERIFQSGER ECRKMFGGCS
VDSDCCAHLG CKPTLKYCAW DGTFGK
