 |
|
 |
| |
| Toxin Name |
μ-theraphotoxin-Phlo1a |
| Source Species |
Phlogius sp. |
| Toxin Group |
Theraphotoxin |
| Description |
Gating modifier toxin that inhibits the human voltage-gated sodium channel NaV1.7 (hNaV1.7) by shifting the threshold for channel activation to more positive potentials. Toxin shifts the V0.5 for hNaV1.7 activation by +3.3 mV at 300 nM and +10 mV at 1 μM. Furthermore, inhibition of hNaV1.7 is voltage-dependent, with lower inhibition at more positive test pulses. μ-TRTX-Phlo1a is a moderately potent inhibitor of hNaV1.7 (IC50 ~ 460 nM) with much lower potency against hNaV1.2 and hNaV1.5 (<20% inhibition at 1 μM peptide).
Sequence and cysteine spacing indicates that μ-TRTX-Phlo1a is an inhibitor cystine knot toxin that belongs to NaSpTx family 2. μ-TRTX-Phlo1a and μ-TRTX-Phlo1b are paralogs that only differ at their C-terminal residue. |
| Discovered |
2014 |
|
Sex: female, Prosoma length: 30mm
Photo courtesy of Eivind Undheim
Use of photo governed by creative
commons noncommercial license
|
| This toxin last updated on Jan 14, 2016 |
|
| Current Taxonomy |
| Kingdom |
Animalia |
| Phylum |
Arthropoda |
| Class |
Arachnida |
| Order |
Araneae |
| Infra-order |
Mygalomorphae |
| Family |
Theraphosidae |
| Genus |
Phlogius |
| Species |
sp. |
|
|
| Molecular Target |
ED50 |
IC50 |
Kd |
Pharmacophore |
Comment |
| Sodium channel, voltage-gated (vertebrate): NaV1.2 |
|
|
|
|
1 μM toxin causes less than 20% inhibition of human Nav1.2 expressed in oocytes. |
| Sodium channel, voltage-gated (vertebrate): NaV1.5 |
|
|
|
|
1 μM toxin causes less than 20% inhibition of human Nav1.5 expressed in oocytes. |
| Sodium channel, voltage-gated (vertebrate): NaV1.7 |
|
459.0
nM
|
|
|
Inhibition of human Nav1.7 expressed in oocytes by native toxin. |
|
| Original Deposition References |
Chow, C.Y., Cristofori-Armstrong, B., Undheim, E.A.B., King, G.F., Rash, L.D.
Toxins 7: 2494-2513 (2015)
Three peptide modulators of the human voltage-gated sodium channel 1.7, an important analgesic target, from the venom of an Australian tarantula
|
| Other References |
Klint J.K., Senff S., Rupasinghe D.B., Er S.Y., Herzig V., Nicholson G.M., King G.F.
Toxicon 60:478-91(2012).
Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads.
|
|
| Disulfide Bonds |
Posttranslational modifications |
| Left Residue |
Right Residue |
Evidence |
| 2 |
16 |
By homology |
| 9 |
21 |
By homology |
| 15 |
29 |
By homology |
|
| Residue Number |
Type |
Symbol |
| 35 |
C-terminal amidation |
NH₂ |
|
|
| Peptide Sequences |
>as:μ-theraphotoxin-Phlo1a Toxin from venom of the spider Phlogius sp. that inhibits the human voltage-gated sodium channel Nav1.7
MKVSVLITLAVLGVMFVWTSAAEQEDHGSDRRDSPALLKNLLGEEVFQSEERACRELLGG
CSKDSDCCAHLECRKKWPYHCVWDWTIGK |
Full BLAST |
BLAST mature toxin only
|
| mRNA Sequences |
>as:μ-theraphotoxin-Phlo1a cDNA sequence encoding the toxin μ-theraphotoxin-Phlo1a from the spider Phlogius sp.
ATGAAGGTTTCAGTACTAATAACTCTTGCTGTATTGGGGGTGATGTTTGTTTGGACTTCT
GCTGCTGAACAAGAAGATCATGGTTCGGATCGAAGGGACTCACCTGCATTGCTAAAAAAT
CTACTAGGGGAAGAAGTATTCCAGTCTGAGGAAAGAGCCTGCAGGGAACTGCTTGGAGGC
TGTAGTAAAGATTCCGATTGCTGTGCACACTTGGAATGCCGAAAAAAGTGGCCATATCAT
TGTGTGTGGGATTGGACCATCGGCAAATGA |
Full BLAST
|
|
| Synonym |
Type |
| μ-theraphotoxin-Phlo1a |
Recommended full name |
| μ-TRTX-Phlo1a |
Recommended abbreviation |
| Phlo1a |
Synonym |
| Phlo1a |
Synonym (abbreviation) |
|
|
|
|
|
 |
|
 |
|
|
