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Peptide record

TPDB34620

Neurotoxin Toxicity standard
62 amino acids
Basic Information
3D PDB MODEL
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TPDB34620
Neurotoxin Toxicity
Toxicity and safety peptides
Peptipedia
standard
No
A 62-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from Peptipedia, with an available 3D structural model.
Sequence
MKTSILFVIFSLALLFALSAATEIEETDRACGQFWWKCGEGKPPCCANFACKIGLYLCIWSP
Physicochemical Analysis
C318H482N74O83S7
H
AL
6894.19
6.22
5
5
30
-0
-2.99
0.589
91.45
Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour
18365
266.38
16
Residue Composition
number
7
A
1
R
1
N
1
D
6
C
4
E
1
Q
4
G
0
H
5
I
7
L
4
K
1
M
5
F
3
P
4
S
3
T
3
W
1
Y
1
V
Amino Acid Distribution
A: 7 R: 1 N: 1 D: 1 C: 6 E: 4 Q: 1 G: 4 H: 0 I: 5 L: 7 K: 4 M: 1 F: 5 P: 3 S: 4 T: 3 W: 3 Y: 1 V: 1
Chemical Descriptors
62
C318H482N74O83S7
6894.19
6.22
-0
-2.99
0.589
Evidence Records 2 records
Evidence 1 Activity

Activity

Neurotoxin
FUNCTION: Moderately inhibits voltage-gated sodium channels and weakly inhibits voltage-gated potassium channel (PubMed:17150181, PubMed:17618665, PubMed:23246579, PubMed:26721415). Inhibits the inactivation of rat Nav1.2/SCN2A (IC(50)=870 nM), rat Nav1.3/SCN3A (IC(50)=845 nM), rat Nav1.4/SCN4A (IC(50)=339 nM), human Nav1.5/SCN5A (IC(50)=335 nM) and human Nav1.7/SCN9A sodium channels (IC(50)=348 nM) (PubMed:26721415). The toxin delays the inactivation of sodium channels without affecting the activation and steady-state inactivation kinetics in the physiological range of voltages (PubMed:26721415). Site-directed mutagenesis of the sodium channel indicates that the toxin interacts with site 3 located at the extracellular S3-S4 linker of domain IV (PubMed:26721415). On potassium channels, it inhibits activation of channels with an IC(50) of 8.05 uM through a voltage sensor-trapping mechanism (PubMed:23246579). It increases muscle contraction in several assays (mouse phrenic nerve-diaphragm, toad heart, rat vas deferens) and is suggested to act both presynaptically and postsynaptically (PubMed:17618665). {ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17618665, ECO:0000269|PubMed:23246579, ECO:0000269|PubMed:26721415}.

Target

voltage-gated sodium channel (Nav) voltage-gated potassium channel (Kv)

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Chilobrachys guangxiensis (Chinese earth tiger tarantula) (Chilobrachys jingzhao)
Neurotoxin Postsynaptic neurotoxin Presynaptic neurotoxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin Voltage-gated sodium channel impairing toxin
Moderately inhibits voltage-gated sodium channels and weakly inhibits voltage-gated potassium channel (PubMed:17150181, PubMed:17618665, PubMed:23246579, PubMed:26721415). Inhibits the inactivation of rat Nav1.2/SCN2A (IC(50)=870 nM), rat Nav1.3/SCN3A (IC(50)=845 nM), rat Nav1.4/SCN4A (IC(50)=339 nM), human Nav1.5/SCN5A (IC(50)=335 nM) and human Nav1.7/SCN9A sodium channels (IC(50)=348 nM) (PubMed:26721415).
Delta-theraphotoxin-Cg1a 2 (Delta-TRTX-Cg1a) (Jingzhaotoxin-1.2) (JZTX-1.2) (Jingzhaotoxin-I.2) (JZTX-I.2) (Peptide F5-24.92)
spider
Neurotoxin 10 (Hwtx-1) family, 33 (Jztx-1) subfamily
Evidence at protein level
Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Postsynaptic neurotoxin Potassium channel impairing toxin Presynaptic neurotoxin Secreted Signal Toxin Voltage-gated potassium channel impairing toxin Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:17476710}.
Evidence 2 Activity

Activity

Neurotoxin
FUNCTION: Inhibits voltage-gated sodium channels, preferentially subtype Nav1.5/SCN5A (in cardiac myocytes), but also Nav1.6/SCN8A and Nav1.7/SCN9A (TTX-sensitive Nav in rat DRG neurons) and invertebrate Nav (in insect neurons) as well as voltage-gated potassium channels of the subtype Kv2.1/KCNB1. Is suggested to bind to site 3 of the sodium channels and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. On potassium channels, inhibits activation of channels with an IC(50) of 8.05 uM through a voltage sensor-trapping mechanism (PubMed:23246579). Increases muscle contraction in several assays (mouse phrenic nerve-diaphragm, toad heart, rat vas deferens) and is suggested to act both presynaptically and postsynaptically. {ECO:0000269|PubMed:15548530, ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17618665, ECO:0000269|PubMed:23246579}. FUNCTION: Moderately inhibits voltage-gated sodium channels and weakly inhibits voltage-gated potassium channel (PubMed:17150181, PubMed:17618665, PubMed:23246579, PubMed:26721415). Inhibits the inactivation of rat Nav1.2/SCN2A (IC(50)=870 nM), rat Nav1.3/SCN3A (IC(50)=845 nM), rat Nav1.4/SCN4A (IC(50)=339 nM), human Nav1.5/SCN5A (IC(50)=335 nM) and human Nav1.7/SCN9A sodium channels (IC(50)=348 nM) (PubMed:26721415). The toxin delays the inactivation of sodium channels without affecting the activation and steady-state inactivation kinetics in the physiological range of voltages (PubMed:26721415). Site-directed mutagenesis of the sodium channel indicates that the toxin interacts with site 3 located at the extracellular S3-S4 linker of domain IV (PubMed:26721415). On potassium channels, it inhibits activation of channels with an IC(50) of 8.05 uM through a voltage sensor-trapping mechanism (PubMed:23246579). It increases muscle contraction in several assays (mouse phrenic nerve-diaphragm, toad heart, rat vas deferens) and is suggested to act both presynaptically and postsynaptically (PubMed:17618665). {ECO:0000269|PubMed:15548530, ECO:0000269|PubMed:17150181, ECO:0000269|PubMed:17618665, ECO:0000269|PubMed:23246579, ECO:0000269|PubMed:26721415}.

Target

voltage-gated sodium channel (Nav) voltage-gated potassium channel (Kv)

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Chilobrachys guangxiensis (Chinese earth tiger tarantula) (Chilobrachys jingzhao)
Neurotoxin Postsynaptic neurotoxin Presynaptic neurotoxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin Voltage-gated sodium channel impairing toxin
Inhibits voltage-gated sodium channels, preferentially subtype Nav1.5/SCN5A (in cardiac myocytes), but also Nav1.6/SCN8A and Nav1.7/SCN9A (TTX-sensitive Nav in rat DRG neurons) and invertebrate Nav (in insect neurons) as well as voltage-gated potassium channels of the subtype Kv2.1/KCNB1. Is suggested to bind to site 3 of the sodium channels and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission.
Delta-theraphotoxin-Cg1a 1 (Delta-TRTX-Cg1a) (Jingzhaotoxin-1) (Jingzhaotoxin-I) (JZTX-I) (Peptide F5-24.92)
spider
Neurotoxin 10 (Hwtx-1) family, 33 (Jztx-1) subfamily
Evidence at protein level
Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Postsynaptic neurotoxin Potassium channel impairing toxin Presynaptic neurotoxin Secreted Signal Toxin Voltage-gated potassium channel impairing toxin Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:15548530}.
Additional Detail Fields 7 fields
Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Postsynaptic neurotoxin Potassium channel impairing toxin Presynaptic neurotoxin Secreted Signal Toxin Voltage-gated potassium channel impairing toxin Voltage-gated sodium channel impairing toxin
Neurotoxin Postsynaptic neurotoxin Presynaptic neurotoxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin Voltage-gated sodium channel impairing toxin
Evidence at protein level
Neurotoxin 10 (Hwtx-1) family, 33 (Jztx-1) subfamily
Delta-theraphotoxin-Cg1a 2 (Delta-TRTX-Cg1a) (Jingzhaotoxin-1.2) (JZTX-1.2) (Jingzhaotoxin-I.2) (JZTX-I.2) (Peptide F5-24.92) Delta-theraphotoxin-Cg1a 1 (Delta-TRTX-Cg1a) (Jingzhaotoxin-1) (Jingzhaotoxin-I) (JZTX-I) (Peptide F5-24.92)
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:17476710}. TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:15548530}.
spider