TPDB

3D PDB MODEL

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TPDB ID TPDB72722

Activity

Neurotoxin

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2

Sequence_Type

standard

Has_Modification No

Description A 72-aa standard natural neurotoxin peptide sequence curated from NTxPred2, with an available 3D structural model.

Sequence

MSGRGFLLLALLLLVTVEATRVEKKHSGILLAWSGPRNRFVRIGRRDMQSPLLSERLRFRALGFRQPSSQKQ

FASTA

>TPDB72722|Neurotoxin|length=72
MSGRGFLLLALLLLVTVEATRVEKKHSGILLAWSGPRNRFVRIGRRDMQSPLLSERLRFRALGFRQPSSQKQ

Formula C368H614N116O95S2

Absent Amino Acids CY

Common Amino Acids L

Mass 8247.76

PI 12.48

Basic Residues 15

Acidic Residues 4

Hydrophobic Residues 30

Net Charge +10

Boman Index 10.34

Hydrophobicity -0.189

Aliphatic Index 102.92

Half Life

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

Extinction Coefficient Cystines 5500

Absorbance 280nm 66.68

Polar Residues 14

number

4

A

11

R

1

N

1

D

0

C

3

E

4

Q

6

G

1

H

2

I

13

L

3

K

2

M

4

F

3

P

7

S

2

T

1

W

0

Y

4

V

Amino Acid Distribution

A: 4 R: 11 N: 1 D: 1 C: 0 E: 3 Q: 4 G: 6 H: 1 I: 2 L: 13 K: 3 M: 2 F: 4 P: 3 S: 7 T: 2 W: 1 Y: 0 V: 4

Length

72

Formula

C368H614N116O95S2

Mass

8247.76

PI

12.48

Net Charge

+10

Boman Index

10.34

Hydrophobicity

-0.189

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: This peptide activates human sensory neuron-specific G-protein coupled receptors MRGPRX1, but not mouse receptors (EC(50)=0.54 uM) (PubMed:30243794, PubMed:37591889). Compared with the agonist chloroquine (anti-malaria drug), it is 600-fold more potent (PubMed:30243794). In vivo, induces itch sensation, since intradermal cheek injection into humanized transgenic mouse (mouse MRGPRX1 replaced by human MRGPRX1) induces scratching (PubMed:30243794). In vivo, treatment of zebrafish larvae with high doses (10 uM) induces hypoactivity at the beginning of the experiment during the dark phase and hyperactivity in the strobe phase after one hour, even after the removal of the toxin from the solution (PubMed:33764053). {ECO:0000269|PubMed:30243794, ECO:0000269|PubMed:33764053, ECO:0000269|PubMed:37591889}.

Target

Target or Channel proton-gated sodium channel / ASIC

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Conus textile (Cloth-of-gold cone)

Neurotoxin Type Neurotoxin G-protein coupled receptor impairing toxin

Mechanism

This peptide activates human sensory neuron-specific G-protein coupled receptors MRGPRX1, but not mouse receptors (EC(50)=0.54 uM) (PubMed:30243794, PubMed:37591889). Compared with the agonist chloroquine (anti-malaria drug), it is 600-fold more potent (PubMed:30243794).

Protein Name Conorfamide-Tx2 (CNF-Tx2) (Cono-RFamide-Tx2)

Venom Taxon Group cone snail

Protein Family FARP (FMRFamide related peptide) family

Protein Existence Evidence at protein level

Keywords 3D-structure Amidation Cleavage on pair of basic residues G-protein coupled receptor impairing toxin Neurotoxin Secreted Signal Toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305|PubMed:30243794}.

Keywords

3D-structure Amidation Cleavage on pair of basic residues G-protein coupled receptor impairing toxin Neurotoxin Secreted Signal Toxin

Neurotoxin_Type

Neurotoxin G-protein coupled receptor impairing toxin

Protein_Existence

Evidence at protein level

Protein_Family

FARP (FMRFamide related peptide) family

Protein_Name

Conorfamide-Tx2 (CNF-Tx2) (Cono-RFamide-Tx2)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305|PubMed:30243794}.

Venom_Taxon_Group

cone snail