TPDB

3D PDB MODEL

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TPDB ID TPDB30231

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2 Peptipedia ToxinPred 3.0

Sequence_Type

standard

Has_Modification No

Description A 34-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2, Peptipedia, and ToxinPred 3.0, with an available 3D structural model.

Sequence

ECRYLFGGCKTTADCCKHLGCRTDLYYCAWDGTF

FASTA

>TPDB30231|Neurotoxin;Toxicity|length=34
ECRYLFGGCKTTADCCKHLGCRTDLYYCAWDGTF

Formula C169H247N45O50S6

Absent Amino Acids NQIMPSV

Common Amino Acids C

Mass 3901.45

PI 6.75

Basic Residues 5

Acidic Residues 4

Hydrophobic Residues 11

Net Charge -0

Boman Index 0.48

Hydrophobicity -0.224

Aliphatic Index 40.29

Half Life

Mammalian: 1 hour Yeast: 30 min E.coli: >10 hour

Extinction Coefficient Cystines 10345

Absorbance 280nm 265.16

Polar Residues 13

number

2

A

2

R

0

N

3

D

6

C

1

E

0

Q

4

G

1

H

0

I

3

L

2

K

0

M

2

F

0

P

0

S

4

T

1

W

3

Y

0

V

Amino Acid Distribution

A: 2 R: 2 N: 0 D: 3 C: 6 E: 1 Q: 0 G: 4 H: 1 I: 0 L: 3 K: 2 M: 0 F: 2 P: 0 S: 0 T: 4 W: 1 Y: 3 V: 0

Length

34

Formula

C169H247N45O50S6

Mass

3901.45

PI

6.75

Net Charge

-0

Boman Index

0.48

Hydrophobicity

-0.224

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: Gating-modifier toxin that potently and selectively acts on Nav1.1/SCN1A and Nav1.3/SCN3A (PubMed:32335140). It enhances hNav1.1/SCN1A currents and delays fast inactivation of the channel (EC(50)=11.6 nM), leading to a sustained current (PubMed:32335140). Similar effects are observed at Nav1.3/SCN3A (EC(50)=11.8 nM), but with less sustained currents (PubMed:32335140). When tested on Nav1.2/SCN2A, the native toxin decreases the peak current by 50% at saturating concentration, whereas the recombinant toxin only shows a weak decrease of peak current (PubMed:32335140). The native toxin specifically activates the voltage-gated sodium channel Nav1.1/SCN1A in somatosensory neurons to elicit acute pain and mechanical allodynia (PubMed:27281198). When tested on Nav1.1/SCN1A, the toxin induces a hyperpolarising shift of the voltage-dependence of steady-state activation, and induces a depolarizing shift in the voltage dependence of inactivation (PubMed:32335140). In addition, it does not modify the recovery from fast inactivation in Nav1.1/SCN1A (PubMed:32335140). The toxin hydrophobic face probably interacts with the domain IV voltage-sensor of Nav1.1/SCN1A and Nav1.3/SCN3A and may trap the voltage-sensing S4 helix in a partially activated state (PubMed:32335140). In vivo, intracerebroventricular injection into mice elicits convulsions, spasms, tremors and rapid death (By similarity). When injected into mouse hindpaw, the toxin elicits an immediate and robust response to pain (PubMed:27281198). However, intraplantar injection of toxin does not cause neurogenic inflammation or alter sensitivity to heat, indicative of a modality-specific effect on mechanosensitive neurons (PubMed:27281198). {ECO:0000250|UniProtKB:P60992, ECO:0000269|PubMed:27281198, ECO:0000269|PubMed:32335140}.

Target

Target or Channel voltage-gated sodium channel (Nav)

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Heteroscodra maculata (Togo starburst tarantula) (Togo starburst baboon spider)

Neurotoxin Type Neurotoxin Ion channel impairing toxin Voltage-gated sodium channel impairing toxin

Mechanism

Gating-modifier toxin that potently and selectively acts on Nav1.1/SCN1A and Nav1.3/SCN3A (PubMed:32335140). It enhances hNav1.1/SCN1A currents and delays fast inactivation of the channel (EC(50)=11.6 nM), leading to a sustained current (PubMed:32335140).

Protein Name Delta-theraphotoxin-Hm1b (Delta-TRTX-Hm1b)

Venom Taxon Group spider

Protein Family Neurotoxin 10 (Hwtx-1) family, 09 (HaTx) subfamily

Protein Existence Evidence at protein level

Keywords 3D-structure Amidation Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Pharmaceutical Secreted Toxin Voltage-gated sodium channel impairing toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:27281198}.

Keywords

3D-structure Amidation Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Pharmaceutical Secreted Toxin Voltage-gated sodium channel impairing toxin

Neurotoxin_Type

Neurotoxin Ion channel impairing toxin Voltage-gated sodium channel impairing toxin

Protein_Existence

Evidence at protein level

Protein_Family

Neurotoxin 10 (Hwtx-1) family, 09 (HaTx) subfamily

Protein_Name

Delta-theraphotoxin-Hm1b (Delta-TRTX-Hm1b)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:27281198}.

Venom_Taxon_Group

spider