P0DQN3 · TXPR1_BUMPU

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).

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.

1355101520253035
ECRYWLGGCSAGQTCCKHLVCSRRHGWCVWDGTFS
TypeIDPosition(s)Description
Site6Pharmacophore for Nav1.7/SCN9A
Site19Pharmacophore for Nav1.7/SCN9A
Site27Pharmacophore for Nav1.7/SCN9A
Site29Pharmacophore for Nav1.7/SCN9A
Site30Pharmacophore for Nav1.7/SCN9A
Site31Pharmacophore for Nav1.7/SCN9A

GO annotations

AspectTerm
Cellular Componentextracellular region
Molecular Functioncalcium channel regulator activity
Molecular Functionion channel inhibitor activity
Molecular Functionpotassium channel regulator activity
Molecular Functionsodium channel regulator activity
Molecular Functiontoxin activity

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Beta/omega-theraphotoxin-Bp1a
  • Short names
    Beta/omega-TRTX-Bp1a
  • Alternative names
    • Protoxin-I analog
      (ProTx-I analog
      )

Organism names

Accessions

  • Primary accession
    P0DQN3

Subcellular Location

Keywords

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.

TypeIDPosition(s)Description
Mutagenesis6Decrease in ability to inhibit Nav1.7/SCN9A.
Mutagenesis17Decrease in ability to inhibit Nav1.2/SCN2A, Nav1.5/SCN5A, Nav1.6/SCN8A and Nav1.7/SCN9A.
Mutagenesis19Decrease in ability to inhibit Nav1.7/SCN9A.
Mutagenesis27Decrease in ability to inhibit Nav1.7/SCN9A.
Mutagenesis29Decrease in ability to inhibit Nav1.7/SCN9A.
Mutagenesis30Decrease in ability to inhibit Nav1.7/SCN9A.
Mutagenesis31Decrease in ability to inhibit Nav1.7/SCN9A.

PTM/Processing

Features

Showing features for peptide, disulfide bond.

TypeIDPosition(s)Description
PeptidePRO_00004514531-35Beta/omega-theraphotoxin-Bp1a
Disulfide bond2↔16
Disulfide bond9↔21
Disulfide bond15↔28

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

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

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    35
  • Mass (Da)
    3,994
  • Last updated
    2020-12-02 v1
  • Checksum
    13F35B2F3A59B2A5
ECRYWLGGCSAGQTCCKHLVCSRRHGWCVWDGTFS

Keywords

Similar Proteins

Disclaimer

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