TPDB

3D PDB MODEL

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TPDB ID TPDB35735

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2 Peptipedia

Sequence_Type

standard

Has_Modification No

Description A 89-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2 and Peptipedia, with an available 3D structural model.

Sequence

MVNMKASMFLALAGLVLLFVVCYASESEEKEFSNELLSSVLAVDDNSKGEERECLEIFKACNPSNDQCCKSSKLVCSRKTRWCKYQIGK

FASTA

>TPDB35735|Neurotoxin;Toxicity|length=89
MVNMKASMFLALAGLVLLFVVCYASESEEKEFSNELLSSVLAVDDNSKGEERECLEIFKACNPSNDQCCKSSKLVCSRKTRWCKYQIGK

Formula C433H699N115O135S10

Absent Amino Acids H

Common Amino Acids S

Mass 9996.60

PI 6.37

Basic Residues 12

Acidic Residues 12

Hydrophobic Residues 35

Net Charge -0

Boman Index 21.15

Hydrophobicity -0.104

Aliphatic Index 82.13

Half Life

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

Extinction Coefficient Cystines 8855

Absorbance 280nm 88.58

Polar Residues 28

number

6

A

3

R

5

N

3

D

7

C

9

E

2

Q

3

G

0

H

2

I

10

L

9

K

3

M

4

F

1

P

11

S

1

T

1

W

2

Y

7

V

Amino Acid Distribution

A: 6 R: 3 N: 5 D: 3 C: 7 E: 9 Q: 2 G: 3 H: 0 I: 2 L: 10 K: 9 M: 3 F: 4 P: 1 S: 11 T: 1 W: 1 Y: 2 V: 7

Length

89

Formula

C433H699N115O135S10

Mass

9996.60

PI

6.37

Net Charge

-0

Boman Index

21.15

Hydrophobicity

-0.104

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: This lethal neurotoxin (without cyclization at position 53) inhibits neuronal voltage-gated sodium channel Nav1.2/SCN2A (IC(50)=10-150 nM), rNav1.3/SCN3A (IC(50)=338 nM), Nav1.6/SCN8A (IC(50)=117 nM), and hNav1.7/SCN9A (IC(50)=9.6-33 nM) (PubMed:18628201, PubMed:20855463, PubMed:23760503, PubMed:25658507, PubMed:29703751, PubMed:31234412). It inhibits activation of sodium channel by trapping the voltage sensor of domain II (DIIS4) in the closed configuration (PubMed:18628201, PubMed:23760503). The toxin neither shifts the Nav1.7/SCN9A activation curve nor modifies the slope factor (PubMed:20855463). It does not slow fast-inactivation of hNav1.7/SCN9A channels (PubMed:20855463). In addition, it has only a weak affinity for lipid membranes (PubMed:18054060, PubMed:28115115, PubMed:29703751). This toxin also exists with a pyroglutamate at position 53 (PubMed:23826086). The sole difference observed between modified (mHwTx-IV) and unmodified toxins is that moderate or high depolarization voltages (200 mV) permit the unmodified toxin to dissociate, whereas mHwTx-IV toxin does not dissociate, even at high depolarization voltages (PubMed:23826086). These data indicate that mHwTx-IV strongly binds to voltage sensor of sodium channel even at extreme depolarization voltages (PubMed:23826086). {ECO:0000269|PubMed:12228241, ECO:0000269|PubMed:18054060, ECO:0000269|PubMed:18628201, ECO:0000269|PubMed:20855463, ECO:0000269|PubMed:21659528, ECO:0000269|PubMed:23523779, ECO:0000269|PubMed:23760503, ECO:0000269|PubMed:25658507, ECO:0000269|PubMed:28115115, ECO:0000269|PubMed:29483648}.

Target

Target or Channel voltage-gated sodium channel (Nav)

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti)

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

Mechanism

This lethal neurotoxin (without cyclization at position 53) inhibits neuronal voltage-gated sodium channel Nav1.2/SCN2A (IC(50)=10-150 nM), rNav1.3/SCN3A (IC(50)=338 nM), Nav1.6/SCN8A (IC(50)=117 nM), and hNav1.7/SCN9A (IC(50)=9.6-33 nM) (PubMed:18628201, PubMed:20855463, PubMed:23760503, PubMed:25658507, PubMed:29703751, PubMed:31234412). It inhibits activation of sodium channel by trapping the voltage sensor of domain II (DIIS4) in the closed configuration (PubMed:18628201, PubMed:23760503).

Protein Name

Huwentoxin-IV (HwTx-IV) (Huwentoxin-4) (Huwentoxin-IVa) (HWTX-IVa) (Huwentoxin-IVb) (HWTX-IVb) (Huwentoxin-IVc) (HWTX-IVc) (Mu-theraphotoxin-Hs2a) (Mu-TRTX-Hs2a)

Venom Taxon Group spider

Protein Family Neurotoxin 10 (Hwtx-1) family, 22 (Htx-4) subfamily

Protein Existence Evidence at protein level

Keywords 3D-structure Amidation Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Presynaptic neurotoxin Pyrrolidone carboxylic acid Secreted Signal Toxin Voltage-gated sodium channel impairing toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:12228241}.

Keywords

3D-structure Amidation Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Presynaptic neurotoxin Pyrrolidone carboxylic acid Secreted Signal Toxin Voltage-gated sodium channel impairing toxin

Neurotoxin_Type

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

Protein_Existence

Evidence at protein level

Protein_Family

Neurotoxin 10 (Hwtx-1) family, 22 (Htx-4) subfamily

Protein_Name

Huwentoxin-IV (HwTx-IV) (Huwentoxin-4) (Huwentoxin-IVa) (HWTX-IVa) (Huwentoxin-IVb) (HWTX-IVb) (Huwentoxin-IVc) (HWTX-IVc) (Mu-theraphotoxin-Hs2a) (Mu-TRTX-Hs2a)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:12228241}.

Venom_Taxon_Group

spider