TPDB

3D PDB MODEL

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TPDB ID TPDB27777

Activity

Neurotoxin Toxicity

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2 pep-lab Peptipedia ToxinPred 3.0

Sequence_Type

standard

Has_Modification No

Description A 33-aa standard natural multi-activity (Neurotoxin and Toxicity) peptide sequence curated from NTxPred2, pep-lab, Peptipedia, and other sources, with an available 3D structural model.

Sequence

GDCLPHLKRCKADNDCCGKKCKRRGTNAEKRCR

FASTA

>TPDB27777|Neurotoxin;Toxicity|length=33
GDCLPHLKRCKADNDCCGKKCKRRGTNAEKRCR

Formula C148H260N58O45S6

Absent Amino Acids QIMFSWYV

Common Amino Acids CK

Mass 3764.41

PI 9.67

Basic Residues 12

Acidic Residues 4

Hydrophobic Residues 4

Net Charge +7

Boman Index 15.22

Hydrophobicity -1.436

Aliphatic Index 29.70

Half Life

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

Extinction Coefficient Cystines 375

Absorbance 280nm 9.96

Polar Residues 9

number

2

A

5

R

2

N

3

D

6

C

1

E

0

Q

3

G

1

H

0

I

2

L

6

K

0

M

0

F

1

P

0

S

1

T

0

W

0

Y

0

V

Amino Acid Distribution

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

Length

33

Formula

C148H260N58O45S6

Mass

3764.41

PI

9.67

Net Charge

+7

Boman Index

15.22

Hydrophobicity

-1.436

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: This toxin affects the activity of ryanodine receptors 1, 2 and 3 (RyR1, RyR2 and RyR3) (PubMed:11867448, PubMed:1334561, PubMed:9565405). At lower concentrations the toxin increases full openings of the RyRs, and at higher concentrations it inhibits full openings and induces openings to subconductance levels (30% of the full conductance state) and reduces the number of full conductance openings (PubMed:27114612, PubMed:9565405). The different actions may be attributed to the toxins binding at different sites on the RyRs, with binding at a high-affinity site mediating the increase in full openings and the induction of subconductance states evoked upon binding to a lower-affinity site (PubMed:14699105). Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.7 nM are enough to induce a sharp release, and 70% of the total calcium is released after toxin (100 nM) addition) probably by acting as a cell-penetrating peptide (CPP) (PubMed:1334561, PubMed:27114612). In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC(50)=8.7 nM) (PubMed:27114612). It also augments the bell-shaped calcium-[3H]ryanodine binding curve that is maximal at about 10 uM calcium concentration (PubMed:27114612). It binds a different site as ryanodine (PubMed:9565405). It acts synergistically with caffeine (By similarity). In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (By similarity). {ECO:0000250|UniProtKB:A0A1L4BJ42, ECO:0000250|UniProtKB:B8QG00, ECO:0000250|UniProtKB:P60254, ECO:0000269|PubMed:11867448, ECO:0000269|PubMed:1334561, ECO:0000269|PubMed:14699105, ECO:0000269|PubMed:9565405}.

Target

Target or Channel voltage-gated calcium channel (Cav) ryanodine receptor

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Pandinus imperator (Emperor scorpion)

Neurotoxin Type Neurotoxin Calcium channel impairing toxin Ion channel impairing toxin Ryanodine-sensitive calcium-release channel impairing toxin

Mechanism

This toxin affects the activity of ryanodine receptors 1, 2 and 3 (RyR1, RyR2 and RyR3) (PubMed:11867448, PubMed:1334561, PubMed:9565405). At lower concentrations the toxin increases full openings of the RyRs, and at higher concentrations it inhibits full openings and induces openings to subconductance levels (30% of the full conductance state) and reduces the number of full conductance openings (PubMed:27114612, PubMed:9565405).

Protein Name Imperacalcin (IpCa) (Imperatoxin activator) (Imperatoxin-A) (IpTxa)

Venom Taxon Group scorpion

Protein Family Scorpion calcin family

Protein Existence Evidence at protein level

Keywords 3D-structure Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Ryanodine-sensitive calcium-release channel impairing toxin Secreted Toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:9108323}.

Keywords

3D-structure Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Ryanodine-sensitive calcium-release channel impairing toxin Secreted Toxin

Neurotoxin_Type

Neurotoxin Calcium channel impairing toxin Ion channel impairing toxin Ryanodine-sensitive calcium-release channel impairing toxin

Protein_Existence

Evidence at protein level

Protein_Family

Scorpion calcin family

Protein_Name

Imperacalcin (IpCa) (Imperatoxin activator) (Imperatoxin-A) (IpTxa)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:9108323}.

Venom_Taxon_Group

scorpion