UniProtKB - P83480 (TXPR1_THRPR)
Protein
Beta/omega-theraphotoxin-Tp1a
Gene
N/A
Organism
Thrixopelma pruriens (Peruvian green velvet tarantula)
Status
Functioni
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) and the nociceptor cation channel TRPA1 (IC50=389 nM) (PubMed:12475222, PubMed:17087985, PubMed:20351484, PubMed:24886690, PubMed:29703751, PubMed:31234412, PubMed:24530065). 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 (PubMed:20351484, PubMed:24886690). 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 (PubMed:24530065). It shows moderate affinity for lipid bilayers (PubMed:29703751).7 Publications
Miscellaneous
The primary structure of the mature peptide is identical to that of Beta/omega-theraphotoxin-Bp1a from Bumba pulcherrimaklaasi (AC P0DQN3).Curated
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 6 | Pharmacophore for Nav1.7/SCN9A1 Publication | 1 | |
Sitei | 19 | Pharmacophore for Nav1.7/SCN9A1 Publication | 1 | |
Sitei | 27 | Pharmacophore for Nav1.7/SCN9A1 Publication | 1 | |
Sitei | 29 | Pharmacophore for Nav1.7/SCN9A1 Publication | 1 | |
Sitei | 30 | Pharmacophore for Nav1.7/SCN9A1 Publication | 1 | |
Sitei | 31 | Pharmacophore for Nav1.7/SCN9A1 Publication | 1 |
GO - Molecular functioni
- calcium channel inhibitor activity Source: UniProtKB
- toxin activity Source: UniProtKB
GO - Biological processi
- pathogenesis Source: InterPro
Keywordsi
Protein family/group databases
TCDBi | 8.B.5.1.1, the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family |
Names & Taxonomyi
Protein namesi | Recommended name: Beta/omega-theraphotoxin-Tp1aCuratedShort name: Beta/omega-TRTX-Tp1aCurated Alternative name(s): Protoxin-1Curated Short name: ProTx-1Curated Short name: ProTx1Curated Protoxin-I2 Publications Short name: ProTx-I7 Publications |
Organismi | Thrixopelma pruriens (Peruvian green velvet tarantula) |
Taxonomic identifieri | 213387 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Theraphosidae › Thrixopelma |
Organism-specific databases
ArachnoServeri | AS000413, beta/omega-theraphotoxin-Tp1a |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Pharmaceutical usei
The amidated mutant G32A (ProTx-I-G32A-NH2) shows a decreased 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.1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 3 | R → A: Reduced ability to inhibit sodium channel Nav1.2/SCN2A. 1 Publication | 1 | |
Mutagenesisi | 5 | W → A: Reduced ability to inhibit sodium channel Nav1.2/SCN2A. 1 Publication | 1 | |
Mutagenesisi | 6 | L → A: Decrease in ability to inhibit Nav1.7/SCN9A. 1 Publication | 1 | |
Mutagenesisi | 13 | Q → A: Reduced ability to inhibit nociceptor cation channel TRPA1. 1 Publication | 1 | |
Mutagenesisi | 17 | K → E: Decrease in ability to inhibit Nav1.2/SCN2A, Nav1.5/SCN5A, Nav1.6/SCN8A and Nav1.7/SCN9A. 1 Publication | 1 | |
Mutagenesisi | 19 | L → A: Decrease in ability to inhibit the channels TRPA1, Nav1.2/SCN2A, and Nav1.7/SCN9A, probably due to improper folding. 2 Publications | 1 | |
Mutagenesisi | 22 | S → A: Reduced ability to inhibit nociceptor cation channel TRPA1. Reduced ability to inhibit sodium channel Nav1.2/SCN2A. 1 Publication | 1 | |
Mutagenesisi | 23 | R → A: Reduced ability to inhibit sodium channel Nav1.2/SCN2A. 1 Publication | 1 | |
Mutagenesisi | 27 | W → A: Decrease in ability to inhibit Nav1.2/SCN2A and Nav1.7/SCN9A. 2 Publications | 1 | |
Mutagenesisi | 29 | V → A: Decrease in ability to inhibit Nav1.2/SCN2A and Nav1.7/SCN9A. 2 Publications | 1 | |
Mutagenesisi | 30 | W → A: Decrease in ability to inhibit the channels TRPA1, Nav1.2/SCN2A and Nav1.7/SCN9A. 2 Publications | 1 | |
Mutagenesisi | 31 | D → A: Decrease in ability to inhibit Nav1.2/SCN2A and Nav1.7/SCN9A. 2 Publications | 1 | |
Mutagenesisi | 32 | G → A: Reduced ability to inhibit sodium channel Nav1.2/SCN2A. 1 Publication | 1 | |
Mutagenesisi | 34 | F → A: Reduced ability to inhibit nociceptor cation channel TRPA1. Reduced ability to inhibit sodium channel Nav1.2/SCN2A. 1 Publication | 1 | |
Mutagenesisi | 35 | S → A: Reduced ability to inhibit nociceptor cation channel TRPA1. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PeptideiPRO_0000045029 | 1 – 35 | Beta/omega-theraphotoxin-Tp1a1 PublicationAdd BLAST | 35 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 2 ↔ 16 | Combined sources1 Publication | ||
Disulfide bondi | 9 ↔ 21 | Combined sources1 Publication | ||
Disulfide bondi | 15 ↔ 28 | Combined sources1 Publication |
Post-translational modificationi
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 Nav1.6/SCN8A.1 Publication
Keywords - PTMi
Disulfide bondExpressioni
Tissue specificityi
Expressed by the venom gland.1 Publication
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P83480 |
SMRi | P83480 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.1 Publication
Sequence similaritiesi
Keywords - Domaini
KnottinFamily and domain databases
InterProi | View protein in InterPro IPR011696, Huwentoxin-1 |
Pfami | View protein in Pfam PF07740, Toxin_12, 1 hit |
i Sequence
Sequence statusi: Complete.
Mass spectrometryi
Molecular mass is 3988.3 Da. Determined by ESI. 1 Publication
Similar proteinsi
Cross-referencesi
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2M9L | NMR | - | A | 1-35 | [»] | |
BMRBi | P83480 | |||||
SMRi | P83480 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein family/group databases
TCDBi | 8.B.5.1.1, the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family |
Organism-specific databases
ArachnoServeri | AS000413, beta/omega-theraphotoxin-Tp1a |
Family and domain databases
InterProi | View protein in InterPro IPR011696, Huwentoxin-1 |
Pfami | View protein in Pfam PF07740, Toxin_12, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TXPR1_THRPR | |
Accessioni | P83480Primary (citable) accession number: P83480 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 15, 2002 |
Last sequence update: | November 15, 2002 | |
Last modified: | December 2, 2020 | |
This is version 75 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, PharmaceuticalDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families