TPDB

3D PDB MODEL

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TPDB ID TPDB27754

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2 Peptipedia pep-lab ToxinPred 3.0

Sequence_Type

standard

Has_Modification No

Description A 30-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2, Peptipedia, pep-lab, and other sources, with an available 3D structural model.

Sequence

YCQKWMWTCDSERKCCEGMVCRLWCKKKLW

FASTA

>TPDB27754|Neurotoxin;Toxicity|length=30
YCQKWMWTCDSERKCCEGMVCRLWCKKKLW

Formula C168H256N46O41S8

Absent Amino Acids ANHIFP

Common Amino Acids C

Mass 3832.64

PI 8.58

Basic Residues 7

Acidic Residues 3

Hydrophobic Residues 10

Net Charge +4

Boman Index 1.41

Hydrophobicity -0.623

Aliphatic Index 35.67

Half Life

Mammalian: 2.8 hour Yeast: 10 min E.coli: 2 min

Extinction Coefficient Cystines 23865

Absorbance 280nm 622.68

Polar Residues 10

number

0

A

2

R

0

N

1

D

6

C

2

E

1

Q

1

G

0

H

0

I

2

L

5

K

2

M

0

F

0

P

1

S

1

T

4

W

1

Y

1

V

Amino Acid Distribution

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

Length

30

Formula

C168H256N46O41S8

Mass

3832.64

PI

8.58

Net Charge

+4

Boman Index

1.41

Hydrophobicity

-0.623

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: Gating-modifier toxin that targets voltage-gated sodium channels with a selective activity on Nav1.7/SCN9A (IC(50)=1-1.5 nM) (PubMed:25026046, PubMed:31234412). It inhibits both activation and inactivation (PubMed:20855463). For inhibition of activation, it is 100-fold more selective for Nav1.7/SCN9A (IC(50)=0.26-3) than for other sodium channels (Nav1.2/SCN2A (IC(50)=40-540 nM), Nav1.3/SCN3A (IC(50)=102 nM), Nav1.4/SCN4A (IC(50)=30-39 nM), Nav1.5/SCN5A (IC(50)=19-90 nM), Nav1.6/SCN8A (IC(50)=26 nM), and Nav1.8/SCN10A (IC(50)=146 nM)) (PubMed:12475222, PubMed:17087985, PubMed:18156314, PubMed:18728100, PubMed:20855463, PubMed:25658507, PubMed:27311819, PubMed:30661758). For inhibition of inactivation, it is 20-fold more potent in inhibiting inactivation on Nav1.7/SCN9A (IC(50)=250 nM) than other channels (about 4.6 uM for all channels) (PubMed:20855463). It also weakly inhibits Cav1.2/CACNA1C and Cav3.2/CACNA1H (29% block at 1 uM) (PubMed:17087985, PubMed:20600227, PubMed:24886690). It inhibits Nav1.7/SCN9A activation by interacting with DII and impairs Nav1.7/SCN9A inactivation by interacting with DIV (PubMed:20855463). It docks on top of the DII S3 helix Nav1.7/SCN9A (PubMed:30661758, PubMed:30765606). It is about 60-fold less active on Nav1.7/SCN9A at depolarized potential (0 mV IC(50)=15 nM), compared to -120 mV potential (IC(50)=0.26 nM) (PubMed:30661758). This toxin binds to lipid membrane (PubMed:15632158, PubMed:27311819). This ability correlates with hNav1.7/SCN9A inhibition, showing that membrane binding is the first step in the inhibitory mechanism of this toxin (PubMed:27311819). It inhibits Nav1.2/SCN2A less potently when it is coexpressed with SCN2B or SCN4B than when it is expressed alone, showing that beta subunits (SCN2B and SCN4B) have a protective effect (PubMed:24297919, PubMed:26894959). {ECO:0000269|PubMed:12475222, ECO:0000269|PubMed:15632158, ECO:0000269|PubMed:17087985, ECO:0000269|PubMed:17339321, ECO:0000269|PubMed:18156314, ECO:0000269|PubMed:18657562, ECO:0000269|PubMed:18728100, ECO:0000269|PubMed:20855463, ECO:0000269|PubMed:24886690, ECO:0000269|PubMed:25658507, ECO:0000269|PubMed:26894959, ECO:0000269|PubMed:27311819, ECO:0000269|PubMed:30765606}.

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 Thrixopelma pruriens (Peruvian green velvet 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

Gating-modifier toxin that targets voltage-gated sodium channels with a selective activity on Nav1.7/SCN9A (IC(50)=1-1.5 nM) (PubMed:25026046, PubMed:31234412). It inhibits both activation and inactivation (PubMed:20855463).

Protein Name Beta/omega-theraphotoxin-Tp2a (Beta/omega-TRTX-Tp2a) (Protoxin-2) (ProTx-2) (ProTx2) (Protoxin-II) (PT-II) (ProTx-II)

Venom Taxon Group spider

Protein Family Neurotoxin 30 (phrixotoxin) family

Protein Existence Evidence at protein level

Keywords 3D-structure Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Lipid-binding Neurotoxin Pharmaceutical 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:12475222}.

Keywords

3D-structure Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Lipid-binding Neurotoxin Pharmaceutical 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 30 (phrixotoxin) family

Protein_Name

Beta/omega-theraphotoxin-Tp2a (Beta/omega-TRTX-Tp2a) (Protoxin-2) (ProTx-2) (ProTx2) (Protoxin-II) (PT-II) (ProTx-II)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:12475222}.

Venom_Taxon_Group

spider