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Peptide record

TPDB72155

Neurotoxin standard
74 amino acids
Basic Information
3D PDB MODEL
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TPDB72155
Neurotoxin
Toxicity and safety peptides
NTxPred2
standard
No
A 74-aa standard natural neurotoxin peptide sequence curated from NTxPred2, with an available 3D structural model.
Sequence
MKTSSLTIIFIAVIITIICLNIHDIEAREIEFNAGRVVRSEKDCIKHLQRCRENKDCCSKKCSRRGTNPEKRCR
Physicochemical Analysis
C363H621N117O107S8
WY
I
8593.12
9.29
18
9
23
+7
26.33
-0.385
89.59
Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour
375
4.36
21
Residue Composition
number
3
A
9
R
4
N
3
D
7
C
6
E
1
Q
2
G
2
H
11
I
3
L
7
K
1
M
2
F
1
P
5
S
4
T
0
W
0
Y
3
V
Amino Acid Distribution
A: 3 R: 9 N: 4 D: 3 C: 7 E: 6 Q: 1 G: 2 H: 2 I: 11 L: 3 K: 7 M: 1 F: 2 P: 1 S: 5 T: 4 W: 0 Y: 0 V: 3
Chemical Descriptors
74
C363H621N117O107S8
8593.12
9.29
+7
26.33
-0.385
Evidence Records 1 records
Evidence 1 Activity

Activity

Neurotoxin
FUNCTION: This toxin activates ryanodine receptors RyR1 and RyR2 by inducing a long-lasting subconductance state (35% of the full conductance stateon RyR1) (PubMed:19389159, PubMed:27114612). Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.8 nM are enough to induce a sharp release on RyR1, and 55% of the total calcium is released after toxin (100 nM) addition on RyR1) probably by acting as a cell-penetrating peptide (CPP) (PubMed:19389159). In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC(50)=14.8 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 (By similarity). It acts synergistically with caffeine (PubMed:19389159). In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (By similarity). {ECO:0000250|UniProtKB:A0A1L4BJ42, ECO:0000250|UniProtKB:P59868, ECO:0000250|UniProtKB:P60254, ECO:0000269|PubMed:19389159, ECO:0000269|PubMed:27114612, ECO:0000269|Ref.2}.

Target

voltage-gated calcium channel (Cav) ryanodine receptor

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Hoffmannihadrurus gertschi (Scorpion) (Hadrurus gertschi)
Neurotoxin Calcium channel impairing toxin Ion channel impairing toxin Ryanodine-sensitive calcium-release channel impairing toxin
This toxin activates ryanodine receptors RyR1 and RyR2 by inducing a long-lasting subconductance state (35% of the full conductance stateon RyR1) (PubMed:19389159, PubMed:27114612). Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.8 nM are enough to induce a sharp release on RyR1, and 55% of the total calcium is released after toxin (100 nM) addition on RyR1) probably by acting as a cell-penetrating peptide (CPP) (PubMed:19389159).
Hadrucalcin (HdCa)
scorpion
Scorpion calcin family
Evidence at protein level
Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Ryanodine-sensitive calcium-release channel impairing toxin Secreted Signal Toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:19389159}.
Additional Detail Fields 7 fields
Calcium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Knottin Neurotoxin Ryanodine-sensitive calcium-release channel impairing toxin Secreted Signal Toxin
Neurotoxin Calcium channel impairing toxin Ion channel impairing toxin Ryanodine-sensitive calcium-release channel impairing toxin
Evidence at protein level
Scorpion calcin family
Hadrucalcin (HdCa)
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:19389159}.
scorpion