TPDB

3D PDB MODEL

Drag to rotate. Click a residue or atom to inspect it; the selected residue is highlighted in amber.

TPDB ID TPDB34652

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

Peptipedia

Sequence_Type

standard

Has_Modification No

Description A 82-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from Peptipedia, with an available 3D structural model.

Sequence

MKVAILFLSILVLAVASESIEESRDDFAVEELGRATCAGQDQPCKETCDCCGERGECVCGGPCICRQGYFWIAWYKLANCKK

FASTA

>TPDB34652|Neurotoxin;Toxicity|length=82
MKVAILFLSILVLAVASESIEESRDDFAVEELGRATCAGQDQPCKETCDCCGERGECVCGGPCICRQGYFWIAWYKLANCKK

Formula C390H615N105O119S11

Absent Amino Acids H

Common Amino Acids C

Mass 9031.47

PI 4.62

Basic Residues 9

Acidic Residues 12

Hydrophobic Residues 32

Net Charge -3

Boman Index 15.68

Hydrophobicity 0.091

Aliphatic Index 79.76

Half Life

Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour

Extinction Coefficient Cystines 14605

Absorbance 280nm 161.71

Polar Residues 22

number

8

A

4

R

1

N

4

D

10

C

8

E

3

Q

7

G

0

H

5

I

6

L

5

K

1

M

3

F

2

P

4

S

2

T

2

W

2

Y

5

V

Amino Acid Distribution

A: 8 R: 4 N: 1 D: 4 C: 10 E: 8 Q: 3 G: 7 H: 0 I: 5 L: 6 K: 5 M: 1 F: 3 P: 2 S: 4 T: 2 W: 2 Y: 2 V: 5

Length

82

Formula

C390H615N105O119S11

Mass

9031.47

PI

4.62

Net Charge

-3

Boman Index

15.68

Hydrophobicity

0.091

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: Toxin that is known to potentiate erectile function (PubMed:18397797). It binds voltage-dependently to sodium channels (Nav), inhibits the inactivation of the activated channels and decreases the peak inward current (PubMed:19231838, PubMed:26119670). The toxin delays inactivation of Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A and Nav1.8/SCN10A, slows the inactivation process and decreases the sodium peak amplitude of Nav1.5/SCN5A and Nav1.6/SCN8A (PubMed:26119670). In vivo, it enhances erectile function by inducing the release of nictric oxide (NO): it slows the sodium current, leading to depolarization, which leads to an increase in calcium influx (probably via activation of N-type calcium channels) which in turn activates neuronal NO synthase (nNOS/NOS1), inducing nitric oxide (NO) production (PubMed:20722794, PubMed:21975567). In a final step, NO activates soluble guanylate cyclase (GUCY1A1/GUCY1B1) which in turn increases cGMP formation, resulting in penile erection (PubMed:23583324). It is noteworthy that the toxin does not provoke erection by inhibiting phosphodiesterase type 5 (PDE5A), an enzyme that hydrolysis cGMP (PubMed:23583324). In vivo, it also causes scratching, lacrimation, hypersalivation, sweating and agitation followed by spastic paralysis of the anterior and posterior extremities and death at dose levels of 0.79 mg/mouse (PubMed:1397265, PubMed:16278100). It is insecticidal to the larval and adult forms of the house fly (PubMed:1397265). The toxin also improves cavernosal relaxation in different models where erectile dysfunction is observed, such as deoxycorticosterone-acetate (DOCA)-salt hypertensive rats, mice models for type-1 diabetes, as well as elderly rats (PubMed:18397797, PubMed:21975567, PubMed:22925420). {ECO:0000269|PubMed:1397265, ECO:0000269|PubMed:16278100, ECO:0000269|PubMed:18397797, ECO:0000269|PubMed:19231838, ECO:0000269|PubMed:20722794, ECO:0000269|PubMed:21975567, ECO:0000269|PubMed:22925420, ECO:0000269|PubMed:26119670, ECO:0000305|PubMed:23583324}.

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 Phoneutria nigriventer (Brazilian armed spider) (Ctenus nigriventer)

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

Mechanism

Toxin that is known to potentiate erectile function (PubMed:18397797). It binds voltage-dependently to sodium channels (Nav), inhibits the inactivation of the activated channels and decreases the peak inward current (PubMed:19231838, PubMed:26119670).

Protein Name Delta-ctenitoxin-Pn2a (Delta-CNTX-Pn2a) (Delta-CNTX-Pn1c) (Neurotoxin Tx2-6) (PnTx2-6)

Venom Taxon Group spider

Protein Family Neurotoxin 03 (Tx2) family, 06 subfamily

Protein Existence Evidence at protein level

Keywords Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Pharmaceutical Secreted Signal Toxin Voltage-gated sodium channel impairing toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:1397265}.

Keywords

Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Pharmaceutical Secreted Signal 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 03 (Tx2) family, 06 subfamily

Protein_Name

Delta-ctenitoxin-Pn2a (Delta-CNTX-Pn2a) (Delta-CNTX-Pn1c) (Neurotoxin Tx2-6) (PnTx2-6)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:1397265}.

Venom_Taxon_Group

spider