Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Psalmotoxin-1

Gene
N/A
Organism
Psalmopoeus cambridgei (Trinidad chevron tarantula)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This toxin is a gating modifier that acts principally as an inhibitor on ASIC1a (ASIC isoform 2) and a potentiator on ASIC1b (ASIC isoform 3) (PubMed:10829030, PubMed:15955877, PubMed:21036899). This toxin potently and selectively inhibits rat, mouse and human ASIC1a (IC50=0.35-3.7 nM) (PubMed:10829030, PubMed:15955877, PubMed:21715637, PubMed:26248594, PubMed:21825095). The blockade is rapidly reversible (PubMed:10829030, PubMed:28320941). The toxin acts by shifting its steady-state desensitization to more alkaline pH (0.27 pH unit) (PubMed:15955877, PubMed:16505147). At higher concentrations, it potentiates rat and human ASIC1b and activates chicken ASIC1 by stabilizing the open state of these subtypes (PubMed:16505147, PubMed:21036899, PubMed:19185346, PubMed:24262969, PubMed:22842900). The toxin binds most tightly to the open and the desensitized states of ASIC1a (promoting desensitization), whereas it binds most tightly to the open state of ASIC1b (promoting opening) (PubMed:16505147). The toxin also inhibits mouse ASIC1a-ASIC2b (IC50=2.64 nM) and rat ASIC1a-ASIC2a (PubMed:21715637, PubMed:27277303). It binds to the extracellular domain at subunit interfaces in the acidic pocket with the majority of contacts on the thumb domain of the channel (PubMed:21825095, PubMed:22842900, PubMed:22760635). It is also noteworthy that calcium competes with the toxin, probably by inhibiting binding of the toxin to the channel (PubMed:15955877).13 Publications

Miscellaneous

This peptide is present at only 0.4% abundance in P.cambridgei venom.1 Publication
Does not act on rat and mouse ASIC1a-ASIC2a (PubMed:10829030, PubMed:21715637). Does not act on rat ASIC1a-ASIC3 (PubMed:10829030).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei7Key residue for interaction with ASIC1a3 Publications1
Sitei24Key residue for interaction with ASIC1a3 Publications1
Sitei26Key residue for interaction with ASIC1a3 Publications1
Sitei27Key residue for interaction with ASIC1a3 Publications1
Sitei28Key residue for interaction with ASIC1a3 Publications1
Sitei30Key residue for interaction with ASIC1a3 Publications1

Keywordsi

Molecular functionIon channel impairing toxin, Proton-gated sodium channel impairing toxin, Toxin

Protein family/group databases

TCDBi8.B.10.1.1. the psalmotoxin-1 (pctx1) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Psalmotoxin-14 Publications
Alternative name(s):
PcTx12 Publications
Pi-theraphotoxin-Pc1a1 Publication
Short name:
Pi-TRTX-Pc1a1 Publication
OrganismiPsalmopoeus cambridgei (Trinidad chevron tarantula)
Taxonomic identifieri179874 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaAraneaeMygalomorphaeTheraphosidaePsalmopoeus

Organism-specific databases

ArachnoServeriAS000400. pi-theraphotoxin-Pc1a.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

This toxin has been shown to be neuroprotective in both rodent and porcine models of cerebral ischemia when administered 30 minutes prior to induction of stroke (PubMed:28457973). In addition, a single dose of this toxin (1 ng/kg, i.c.v. 2 h post stroke) does indeed provide substantial neuronal and functional protection in ischemic stroke in conscious hypertensive rats (PubMed:26320544).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 2Missing : 1.6-fold decrease in ability to inhibit rASIC1a channel. 1 Publication2
Mutagenesisi6K → A: 97.7-fold decrease in ability to inhibit rASIC1a channel, probably due to structural perturbations. 1 Publication1
Mutagenesisi7W → A: Complete loss in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi8K → A: 1.7-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi14H → A: No change in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi24W → A: 170-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi25K → A: No change in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi26R → A: Loss of ability to inhibit rASIC1a at low concentration and gain of function as a positive modulator at high concentrations (>100 nM), probably by stabilizing the open state of the channel. 1 Publication1
Mutagenesisi27R → A: 165-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi28R → A: 14.5-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi29S → A: Does not significantly modify the ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi30F → A: Loss of ability to inhibit rASIC1a at low concentration and gain of function as a positive modulator at high concentrations, probably by stabilizing the open state of the channel. 1 Publication1
Mutagenesisi31E → A: 2.2-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi32V → A: 17.9-fold decrease in ability to inhibit rASIC1a channel, probably due to structural perturbations. 1 Publication1
Mutagenesisi34V → A: 1.4-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi35P → A: 2.7-fold increase in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi36K → A: 1.8-fold increase in ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi37T → A: Does not significantly modify the ability to inhibit rASIC1a channel. 1 Publication1
Mutagenesisi38 – 40Missing : 4.1-fold decrease in ability to inhibit rASIC1a channel, probably due to the deletion of P-38. 1 Publication3
Mutagenesisi38P → A: 3.9-fold decrease in ability to inhibit rASIC1a channel. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PeptideiPRO_00000449651 – 40Psalmotoxin-11 PublicationAdd BLAST40

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi3 ↔ 184 PublicationsImported
Disulfide bondi10 ↔ 234 PublicationsImported
Disulfide bondi17 ↔ 334 PublicationsImported

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.1 Publication

Interactioni

Protein-protein interaction databases

DIPiDIP-59909N.

Structurei

Secondary structure

140
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 4Combined sources3
Beta strandi6 – 8Combined sources3
Turni11 – 14Combined sources4
Beta strandi18 – 20Combined sources3
Beta strandi21 – 24Combined sources4
Beta strandi27 – 29Combined sources3
Beta strandi32 – 35Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LMMNMR-A1-40[»]
2KNINMR-A1-40[»]
3S3XX-ray2.99D/E/F2-38[»]
4FZ0X-ray2.80M/N/O1-40[»]
4FZ1X-ray3.36D1-40[»]
ProteinModelPortaliP60514.
SMRiP60514.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP60514.

Family & Domainsi

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.4 Publications

Sequence similaritiesi

Belongs to the psalmotoxin-1 family.Curated

Keywords - Domaini

Knottin

Sequencei

Sequence statusi: Complete.

P60514-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40
EDCIPKWKGC VNRHGDCCEG LECWKRRRSF EVCVPKTPKT
Length:40
Mass (Da):4,695
Last modified:March 1, 2004 - v1
Checksum:iA52DC98962D9598C
GO

Mass spectrometryi

Molecular mass is 4689.25 Da from positions 1 - 40. Determined by MALDI. 1 Publication
Molecular mass is 4690 Da from positions 1 - 40. Determined by MALDI. 1 Publication

Similar proteinsi

Entry informationi

Entry nameiTXP1_PSACA
AccessioniPrimary (citable) accession number: P60514
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: August 30, 2017
This is version 66 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families