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Peptide record

TPDB72501

Neurotoxin standard
46 amino acids
Basic Information
3D PDB MODEL
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TPDB72501
Neurotoxin
Toxicity and safety peptides
NTxPred2
standard
No
A 46-aa standard natural neurotoxin peptide sequence curated from NTxPred2, with an available 3D structural model.
Sequence
MISMLRCIYLFLSVILITSYFVTPVMPCNCKAPETALCARRCQQHG
Physicochemical Analysis
C231H375N61O60S8
DW
CL
5223.37
8.47
5
1
22
+3
-0.22
0.693
101.74
Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour
3230
61.84
16
Residue Composition
number
3
A
3
R
1
N
0
D
5
C
1
E
2
Q
1
G
1
H
4
I
5
L
1
K
3
M
2
F
3
P
3
S
3
T
0
W
2
Y
3
V
Amino Acid Distribution
A: 3 R: 3 N: 1 D: 0 C: 5 E: 1 Q: 2 G: 1 H: 1 I: 4 L: 5 K: 1 M: 3 F: 2 P: 3 S: 3 T: 3 W: 0 Y: 2 V: 3
Chemical Descriptors
46
C231H375N61O60S8
5223.37
8.47
+3
-0.22
0.693
Evidence Records 1 records
Evidence 1 Activity

Activity

Neurotoxin
FUNCTION: Toxin with unique selectivity to KCa2 channels (PubMed:10696100, PubMed:11212219, PubMed:11533126, PubMed:17142458, PubMed:20562108, PubMed:32560481, PubMed:36188602, PubMed:6122211, PubMed:9287325, PubMed:9459560). Potently blocks human, rat and mouse KCa2.2/KCNN2/SK2 channels (IC(50)=27-140 pM), and moderately blocks human and rat KCa2.3/KCNN3/SK3 channels (IC(50)=0.6-4 nM), and human (IC(50)=0.7-12 nM) and mouse (IC(50)=28 nM) KCa2.1/KCNN1/SK1 channels (PubMed:10696100, PubMed:11212219, PubMed:11533126, PubMed:17142458, PubMed:20562108, PubMed:36188602, PubMed:9287325, PubMed:9459560). Does not show any antimicrobial activity (PubMed:36188602). In vivo, intracerebroventricular injection into rats of a dose of 1 ng results in neurodegeneration specifically in the Purkinje cells of the cerebellum, and induces seizures characterized by hypersensitivity to noise, loss of postural control, paroxystic jerking, and alternating periods of great agitation with tonic-clonic convulsions and periods of total prostration (PubMed:9459560). When administered at high doses, exerts anti-inflammatory, anti-oxidative, anti-fibrotic and anti-apoptotic properties in several models of inflammatory disease, including gouty arthritis, atherosclerosis, atopic dermatitis and acute kidney injury (PubMed:28958612, PubMed:32289477, PubMed:32560481, PubMed:33287398). Down-regulates pro-inflammatory signaling pathways, such as the NF-kappaB and STAT3 pathways, probably by blocking SK channels such as KCa2.2/KCNN2/SK2 and/or KCa2.3/KCNN3/SK3 which are thought to be involved in promoting some inflammatory responses (PubMed:28958612, PubMed:32289477, PubMed:32560481, PubMed:33287398). For example in mouse and rat microglia cells, inhibits LPS-activated KCa2.2/KCNN2/SK2 channels and TLR4 expression leading to the down-regulation of the NF-kappaB, STAT, and MAPK/ERK signaling pathways and, as a consequence, decreases secretion of pro-inflammatory cytokines (PubMed:32560481). {ECO:0000269|PubMed:10696100, ECO:0000269|PubMed:11212219, ECO:0000269|PubMed:11533126, ECO:0000269|PubMed:17142458, ECO:0000269|PubMed:19818752, ECO:0000269|PubMed:20562108, ECO:0000269|PubMed:28108814, ECO:0000269|PubMed:28958612, ECO:0000269|PubMed:32289477, ECO:0000269|PubMed:32560481, ECO:0000269|PubMed:33287398, ECO:0000269|PubMed:36188602, ECO:0000269|PubMed:6122211, ECO:0000269|PubMed:9287325, ECO:0000269|PubMed:9459560}.

Target

voltage-gated potassium channel (Kv)

Source & Reference

NA
UniProtKB/Swiss-Prot Tox-Prot

Other

Apis mellifera (Honeybee)
Neurotoxin Calcium-activated potassium channel impairing toxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin
Toxin with unique selectivity to KCa2 channels (PubMed:10696100, PubMed:11212219, PubMed:11533126, PubMed:17142458, PubMed:20562108, PubMed:32560481, PubMed:36188602, PubMed:6122211, PubMed:9287325, PubMed:9459560). Potently blocks human, rat and mouse KCa2.2/KCNN2/SK2 channels (IC(50)=27-140 pM), and moderately blocks human and rat KCa2.3/KCNN3/SK3 channels (IC(50)=0.6-4 nM), and human (IC(50)=0.7-12 nM) and mouse (IC(50)=28 nM) KCa2.1/KCNN1/SK1 channels (PubMed:10696100, PubMed:11212219, PubMed:11533126, PubMed:17142458, PubMed:20562108, PubMed:36188602, PubMed:9287325, PubMed:9459560).
Apamin (APM) (Apamine)
insect
Evidence at protein level
3D-structure Amidation Calcium-activated potassium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Neurotoxin Potassium channel impairing toxin Reference proteome Secreted Signal Toxin Voltage-gated potassium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:7759523}.
Additional Detail Fields 6 fields
3D-structure Amidation Calcium-activated potassium channel impairing toxin Direct protein sequencing Disulfide bond Ion channel impairing toxin Neurotoxin Potassium channel impairing toxin Reference proteome Secreted Signal Toxin Voltage-gated potassium channel impairing toxin
Neurotoxin Calcium-activated potassium channel impairing toxin Ion channel impairing toxin Potassium channel impairing toxin Voltage-gated potassium channel impairing toxin
Evidence at protein level
Apamin (APM) (Apamine)
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:7759523}.
insect