TPDB

3D PDB MODEL

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TPDB ID TPDB40388

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2 ToxinPred 3.0

Sequence_Type

standard

Has_Modification No

Description A 33-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2 and ToxinPred 3.0, with an available 3D structural model.

Sequence

DCLGWFKSCDPKNDKCCKNYSCSRRDRWCKYDL

FASTA

>TPDB40388|Neurotoxin;Toxicity|length=33
DCLGWFKSCDPKNDKCCKNYSCSRRDRWCKYDL

Formula C171H259N51O51S6

Absent Amino Acids AEQHIMTV

Common Amino Acids C

Mass 4037.61

PI 8.30

Basic Residues 8

Acidic Residues 5

Hydrophobic Residues 7

Net Charge +3

Boman Index 5.95

Hydrophobicity -1.239

Aliphatic Index 23.64

Half Life

Mammalian: 1.1 hour Yeast: 3 min E.coli: >10 hour

Extinction Coefficient Cystines 14355

Absorbance 280nm 355.53

Polar Residues 13

number

0

A

3

R

2

N

5

D

6

C

0

E

0

Q

1

G

0

H

0

I

2

L

5

K

0

M

1

F

1

P

3

S

0

T

2

W

2

Y

0

V

Amino Acid Distribution

A: 0 R: 3 N: 2 D: 5 C: 6 E: 0 Q: 0 G: 1 H: 0 I: 0 L: 2 K: 5 M: 0 F: 1 P: 1 S: 3 T: 0 W: 2 Y: 2 V: 0

Length

33

Formula

C171H259N51O51S6

Mass

4037.61

PI

8.30

Net Charge

+3

Boman Index

5.95

Hydrophobicity

-1.239

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: Potent inhibitor of hNav1.7/SCN9A (IC(50)=16 nM, tested in patch-clamp), and modest inhibitor of Cav2.2/CACNA1B (IC(50)~3 uM on rat and human channel) (PubMed:28880874). It also seems to be potent on hNav1.1/SCN1A (IC(50)=2.18 uM), hNav1.2/SCN2A (IC(50)=0.13 uM), hNav1.7/SCN9A (IC(50)=3.34 uM) and hNav1.8/SCN10A (IC(50)=6.92 uM) (tested in fluorimetric assays, which shows results with lower activity than results obtained by patch-clamp) (PubMed:28880874). This toxin inhibits Cav2.2/CACNA1B by acting near the pore region, but without overlapping the omega-conotoxin binding site (PubMed:28880874). It also seems to interfere with inactivation of Cav2.2/CACNA1B with no apparent effects on the activation gating of the channel (PubMed:28880874). Conversely, at Nav1.7/SCN9A it acts as a typical gating modifier toxin, interacting with one or more of the voltage sensor domains and changing the gating properties of this channel (PubMed:28880874). In vivo, it reversibly paralyzes sheep blowflies (PubMed:28880874). In addition, low doses of this toxin (400 pmol) fully reverse Nav1.7/SCN9A-evoked pain behaviors in mice (without side effects), demonstrating its analgesic potential (PubMed:28880874). {ECO:0000269|PubMed:28880874}.

Target

Target or Channel voltage-gated sodium channel (Nav) voltage-gated calcium channel (Cav)

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Ceratogyrus darlingi (Rear horned baboon tarantula)

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

Mechanism

Potent inhibitor of hNav1.7/SCN9A (IC(50)=16 nM, tested in patch-clamp), and modest inhibitor of Cav2.2/CACNA1B (IC(50)~3 uM on rat and human channel) (PubMed:28880874). It also seems to be potent on hNav1.1/SCN1A (IC(50)=2.18 uM), hNav1.2/SCN2A (IC(50)=0.13 uM), hNav1.7/SCN9A (IC(50)=3.34 uM) and hNav1.8/SCN10A (IC(50)=6.92 uM) (tested in fluorimetric assays, which shows results with lower activity than results obtained by patch-clamp) (PubMed:28880874).

Protein Name Beta-theraphotoxin-Cd1a (Beta-TRTX-Cd1a)

Venom Taxon Group spider

Protein Family Neurotoxin 10 (Hwtx-1) family, 04 (CcoTx1) subfamily

Protein Existence Evidence at protein level

Keywords Amidation Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Secreted Toxin Voltage-gated calcium channel impairing toxin Voltage-gated sodium channel impairing toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:28880874}.

Keywords

Amidation Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Secreted Toxin Voltage-gated calcium channel impairing toxin Voltage-gated sodium channel impairing toxin

Neurotoxin_Type

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

Protein_Existence

Evidence at protein level

Protein_Family

Neurotoxin 10 (Hwtx-1) family, 04 (CcoTx1) subfamily

Protein_Name

Beta-theraphotoxin-Cd1a (Beta-TRTX-Cd1a)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:28880874}.

Venom_Taxon_Group

spider