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Peptide record

TPDB39663

Neurotoxin Toxicity standard
34 amino acids
Basic Information
3D PDB MODEL
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TPDB39663
Neurotoxin Toxicity
Toxicity and safety peptides
NTxPred2 ToxinPred 3.0
standard
No
A 34-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2 and ToxinPred 3.0, with an available 3D structural model.
Sequence
ACLGQWDSCDPKASKCCPNYACEWKYPWCRYKLF
Physicochemical Analysis
C183H260N46O48S6
HIMTV
C
4064.72
8.01
5
3
12
+2
-0.70
-0.594
31.76
Mammalian: 4.4 hour Yeast: >20 hour E.coli: >10 hour
21345
525.13
13
Residue Composition
number
3
A
1
R
1
N
2
D
6
C
1
E
1
Q
1
G
0
H
0
I
2
L
4
K
0
M
1
F
3
P
2
S
0
T
3
W
3
Y
0
V
Amino Acid Distribution
A: 3 R: 1 N: 1 D: 2 C: 6 E: 1 Q: 1 G: 1 H: 0 I: 0 L: 2 K: 4 M: 0 F: 1 P: 3 S: 2 T: 0 W: 3 Y: 3 V: 0
Chemical Descriptors
34
C183H260N46O48S6
4064.72
8.01
+2
-0.70
-0.594
Evidence Records 1 records
Evidence 1 Activity

Activity

Neurotoxin
FUNCTION: Voltage-gated sodium channel inhibitor. It is unclear if it selectively inhibits Nav1.7/SCN9A or shows similar potency on all sodium channels tested (PubMed:31234412, PubMed:31443554, Ref.1). According to Escoubas et al., 2006 and Nicolas et al., 2019, it is selective over Nav1.7/SCN9A (90% inhibition at 1 uM), versus Nav1.4 and Nav1.6 (35% inhibition), and shows a small inhibition on all other sodium channels (except Nav1.8/SCN10A) (PubMed:31234412, Ref.1). According to Goncalves et al., 2019, it shows a similar inhibition on almost all sodium channels tested (Nav1.1/SCN1A (IC(50)=280.3 nM), Nav1.2/SCN2A (IC(50)=73.7 nM), Nav1.3/SCN3A (IC(50)=201.5 nM), Nav1.4/SCN4A (IC(50)>2100 nM), Nav1.5/SCN5A (IC(50)=710.6 nM), Nav1.6/SCN8A (IC(50)=491.2 nM), and Nav1.7/SCN9A (IC(50)=254.3-260 nM)), except Nav1.8/SCN10A (PubMed:31443554). The voltage-dependence of steady-state Nav1.7/SCN9A channel activation and inactivation are not affected, suggesting that is does not act as a gating-modifier toxin but rather blocks or impedes ion flux through the channel pore (PubMed:31234412, Ref.1). The toxin effect is partial and poorly reversible (PubMed:31234412). In addition to its inhibition to sodium channels, it also shows a small inhibition on rat Kv3.4/KCNC4 potassium channels (20% inhibition at 1 uM) (PubMed:31234412). In vivo, when tested on pain models, it shows analgesic activity (PubMed:31234412, PubMed:31443554). {ECO:0000269|PubMed:31234412, ECO:0000269|PubMed:31443554, ECO:0000269|Ref.1}.

Target

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

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Phlogiellus sp. (Tarantula)
Neurotoxin Ion channel impairing toxin Voltage-gated sodium channel impairing toxin
Voltage-gated sodium channel inhibitor. It is unclear if it selectively inhibits Nav1.7/SCN9A or shows similar potency on all sodium channels tested (PubMed:31234412, PubMed:31443554, Ref.1).
Mu-theraphotoxin-Pspp1 (Mu-TRTX-Pspp1) (Phlotoxin 1) (PhlTx1)
spider
Neurotoxin 10 (Hwtx-1) family
Evidence at protein level
Amidation Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Pharmaceutical Secreted Toxin Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
Additional Detail Fields 7 fields
Amidation Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Pharmaceutical Secreted Toxin Voltage-gated sodium channel impairing toxin
Neurotoxin Ion channel impairing toxin Voltage-gated sodium channel impairing toxin
Evidence at protein level
Neurotoxin 10 (Hwtx-1) family
Mu-theraphotoxin-Pspp1 (Mu-TRTX-Pspp1) (Phlotoxin 1) (PhlTx1)
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
spider