TPDB

3D PDB MODEL

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TPDB ID TPDB38174

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2 Peptipedia ToxinPred 3.0

Sequence_Type

standard

Has_Modification No

Description A 32-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2, Peptipedia, and ToxinPred 3.0, with an available 3D structural model.

Sequence

SNKRKNAAMLDMIAQHAIRGCCSDPRCRYRCR

FASTA

>TPDB38174|Neurotoxin;Toxicity|length=32
SNKRKNAAMLDMIAQHAIRGCCSDPRCRYRCR

Formula C149H255N57O43S6

Absent Amino Acids EFTWV

Common Amino Acids R

Mass 3725.38

PI 10.20

Basic Residues 9

Acidic Residues 2

Hydrophobic Residues 10

Net Charge +6

Boman Index 8.18

Hydrophobicity -0.831

Aliphatic Index 49.06

Half Life

Mammalian: 1.9 hour Yeast: >20 hour E.coli: >10 hour

Extinction Coefficient Cystines 1740

Absorbance 280nm 46.71

Polar Residues 10

number

4

A

6

R

2

N

2

D

4

C

0

E

1

Q

1

G

1

H

2

I

1

L

2

K

2

M

0

F

1

P

2

S

0

T

0

W

1

Y

0

V

Amino Acid Distribution

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

Length

32

Formula

C149H255N57O43S6

Mass

3725.38

PI

10.20

Net Charge

+6

Boman Index

8.18

Hydrophobicity

-0.831

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: This toxin target two types of receptors, the nicotinic acetylcholine receptor (nAChR) and the G-protein-coupled receptor GABA(B). It specifically inhibits the alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR, with preference for rat receptors (PubMed:16445293, PubMed:18242183, PubMed:18295795, PubMed:21888386, PubMed:22774872, PubMed:25740413, PubMed:28223528). It interacts with the alpha-10(+)/alpha-9(-)interface of the receptor (PubMed:25740413). It shows a two order of magnitude species difference potency for the rat versus human alpha-9-alpha-10 nAChR, due to the Thr-86 located in the alpha-9 nAChR subunit (PubMed:22774872). This toxin also shows inhibition of high voltage-activated (HVA) calcium channels (Cav2.2) by acting on GABA(B) receptors (GABBR1 and GABBR2) (PubMed:18945902, PubMed:21888386). In vivo, this toxin produces an acute antinociceptive effect in peripheral nerve-injured rats, which may be related to the inhibition of immune cell buildup at the site of nerve injury (PubMed:17101979). In addition, when intramuscularly injected into rats following chronic constriction injury of the sciatic nerve, this toxin protects peripheral nervous tissues as well as prevents central maladaptive plasticity by inhibiting glial cell activation (PubMed:25008370). {ECO:0000269|PubMed:16445293, ECO:0000269|PubMed:17101979, ECO:0000269|PubMed:18242183, ECO:0000269|PubMed:18295795, ECO:0000269|PubMed:18945902, ECO:0000269|PubMed:21888386, ECO:0000269|PubMed:22774872, ECO:0000269|PubMed:25008370, ECO:0000269|PubMed:25740413, ECO:0000269|PubMed:28223528}.

Target

Target or Channel nicotinic acetylcholine receptor (nAChR) acetylcholine receptor voltage-gated calcium channel (Cav)

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Conus regius (Crown cone)

Neurotoxin Type Neurotoxin Postsynaptic neurotoxin Acetylcholine receptor inhibiting toxin G-protein coupled receptor impairing toxin Ion channel impairing toxin

Mechanism

This toxin target two types of receptors, the nicotinic acetylcholine receptor (nAChR) and the G-protein-coupled receptor GABA(B). It specifically inhibits the alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR, with preference for rat receptors (PubMed:16445293, PubMed:18242183, PubMed:18295795, PubMed:21888386, PubMed:22774872, PubMed:25740413, PubMed:28223528).

Protein Name Alpha-conotoxin RgIA

Venom Taxon Group cone snail

Protein Family Conotoxin A superfamily

Protein Existence Evidence at protein level

Keywords 3D-structure Acetylcholine receptor inhibiting toxin Disulfide bond G-protein coupled receptor impairing toxin Ion channel impairing toxin Neurotoxin Postsynaptic neurotoxin Secreted Toxin

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

Keywords

3D-structure Acetylcholine receptor inhibiting toxin Disulfide bond G-protein coupled receptor impairing toxin Ion channel impairing toxin Neurotoxin Postsynaptic neurotoxin Secreted Toxin

Neurotoxin_Type

Neurotoxin Postsynaptic neurotoxin Acetylcholine receptor inhibiting toxin G-protein coupled receptor impairing toxin Ion channel impairing toxin

Protein_Existence

Evidence at protein level

Protein_Family

Conotoxin A superfamily

Protein_Name

Alpha-conotoxin RgIA

Tissue_Specificity

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

Venom_Taxon_Group

cone snail