P0DQN3 · TXPR1_BUMPU
- ProteinBeta/omega-theraphotoxin-Bp1a
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Ion channel impairing toxin that inhibits voltage-gated calcium channel Cav3.1/CACNA1G (IC50=53 nM), voltage-gated potassium channels Kv2.1/KCNB1 (IC50=411 nM), all sodium channels tested (Nav1.2/SCN2A (IC50=60-104 nM), Nav1.5/SCN5A (IC50=76-358 nM), Nav1.6/SCN8A (IC50=21-133 nM), Nav1.7/SCN9A (IC50=51-95 nM), and Nav1.8/SCN10A) as well as the nociceptor cation channel TRPA1 (IC50=389 nM) (By similarity) (PubMed:32511987).
Acts as a potent and selective blocker of voltage-gated calcium channel Cav3.1/CACNA1G, but not of Cav3.2/CACNA1H, and Cav3.3/CACNA1I (By similarity).
On Nav1.7/SCN9A, primarily interacts with the DII and DIV voltage-sensor domains (PubMed:32511987).
Also acts as an inhibitor of nociceptor cation channel TRPA1 (IC50~389 nM) by binding to the S1-S4 gating domain of TRPA1 (By similarity).
It shows moderate affinity for lipid bilayers (By similarity).
Acts as a potent and selective blocker of voltage-gated calcium channel Cav3.1/CACNA1G, but not of Cav3.2/CACNA1H, and Cav3.3/CACNA1I (By similarity).
On Nav1.7/SCN9A, primarily interacts with the DII and DIV voltage-sensor domains (PubMed:32511987).
Also acts as an inhibitor of nociceptor cation channel TRPA1 (IC50~389 nM) by binding to the S1-S4 gating domain of TRPA1 (By similarity).
It shows moderate affinity for lipid bilayers (By similarity).
Miscellaneous
The primary structure of the mature peptide is identical to that of ProTx-1 from Thrixopelma pruriens (AC P83480).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 6 | Pharmacophore for Nav1.7/SCN9A | ||||
Sequence: L | ||||||
Site | 19 | Pharmacophore for Nav1.7/SCN9A | ||||
Sequence: L | ||||||
Site | 27 | Pharmacophore for Nav1.7/SCN9A | ||||
Sequence: W | ||||||
Site | 29 | Pharmacophore for Nav1.7/SCN9A | ||||
Sequence: V | ||||||
Site | 30 | Pharmacophore for Nav1.7/SCN9A | ||||
Sequence: W | ||||||
Site | 31 | Pharmacophore for Nav1.7/SCN9A | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Molecular Function | calcium channel regulator activity | |
Molecular Function | ion channel inhibitor activity | |
Molecular Function | potassium channel regulator activity | |
Molecular Function | sodium channel regulator activity | |
Molecular Function | toxin activity |
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameBeta/omega-theraphotoxin-Bp1a
- Short namesBeta/omega-TRTX-Bp1a
- Alternative names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Chelicerata > Arachnida > Araneae > Mygalomorphae > Theraphosidae > Bumba
Accessions
- Primary accessionP0DQN3
Subcellular Location
Phenotypes & Variants
Pharmaceutical
The amidated mutant G32A (ProTx-I-G32A-NH2) shows a decreased toxin ability to inhibit all sodium channels tested, with a more pronounced reduction on Nav1.2/SCN2A and Nav1.5/SCN5A. As a consequence, this mutant shows an enhanced selectivity and potency for Nav1.7/SCN9A, and thus may provide a good starting point for second generation analogs to treat pain.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 6 | Decrease in ability to inhibit Nav1.7/SCN9A. | ||||
Sequence: L → A | ||||||
Mutagenesis | 17 | Decrease in ability to inhibit Nav1.2/SCN2A, Nav1.5/SCN5A, Nav1.6/SCN8A and Nav1.7/SCN9A. | ||||
Sequence: K → E | ||||||
Mutagenesis | 19 | Decrease in ability to inhibit Nav1.7/SCN9A. | ||||
Sequence: L → A | ||||||
Mutagenesis | 27 | Decrease in ability to inhibit Nav1.7/SCN9A. | ||||
Sequence: W → A | ||||||
Mutagenesis | 29 | Decrease in ability to inhibit Nav1.7/SCN9A. | ||||
Sequence: V → A | ||||||
Mutagenesis | 30 | Decrease in ability to inhibit Nav1.7/SCN9A. | ||||
Sequence: W → A | ||||||
Mutagenesis | 31 | Decrease in ability to inhibit Nav1.7/SCN9A. | ||||
Sequence: D → A |
PTM/Processing
Features
Showing features for peptide, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Peptide | PRO_0000451453 | 1-35 | Beta/omega-theraphotoxin-Bp1a | |||
Sequence: ECRYWLGGCSAGQTCCKHLVCSRRHGWCVWDGTFS | ||||||
Disulfide bond | 2↔16 | |||||
Sequence: CRYWLGGCSAGQTCC | ||||||
Disulfide bond | 9↔21 | |||||
Sequence: CSAGQTCCKHLVC | ||||||
Disulfide bond | 15↔28 | |||||
Sequence: CCKHLVCSRRHGWC |
Post-translational modification
An unnatural amidation at Ser-35 provokes a 14-fold increased toxin ability to inhibit Nav1.2/SCN2A and a ~2-fold decreased toxin ability to inhibit both Nav1.5/SCN5A and Nav1.7/SCN9A.
Keywords
- PTM
Expression
Tissue specificity
Expressed by the venom gland.
Structure
Family & Domains
Domain
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Sequence similarities
Belongs to the neurotoxin 10 (Hwtx-1) family. 54 (ProTx-1) subfamily.
Keywords
- Domain