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104  structures 2  species 0  interactions 5  sequences 1  architecture

Family: Toxin_2 (PF00451)

Summary: Scorpion short toxin, BmKK2

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Agitoxin". More...

Agitoxin Edit Wikipedia article


Agitoxin is found in the venom of the scorpion Leiurus quinquestriatus herbraeus (yellow scorpion)


Agitoxin can be purified using HPLC techniques. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form to the core of the molecule 3 types of agitoxin can be distinguished. All 3 agitoxins have been identified as 38 aminoacid toxins

Agitoxin-1: Gly-Val-Pro-Ile-Asn-Val-Lys-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Leu-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Ile-Asn-Gly-Lys-Cys-His-Cys-Thr-Pro-Lys (mol. Weight=4201 Da)

Agitoxin-2: Gly-Val-Pro-Ile-Asn-Val-Ser-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Ile-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Met-Asn-Arg-Lys-Cys-His-Cys-Thr-Pro-Lys (mol. Weight=4090.0 Da) Molecular Formula= C169H278N54O48S8

Agitoxin-3: Gly-Val-Pro-Ile-Asn-Val-Pro-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Ile-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Met-Asn-Arg-Lys-Cys-His-Cys-Thr-Pro-Lys

The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins.


Agitoxin binds to the shaker K+ channel in drosophila as well as to the mammalian homologue of shaker

Mode of action

Agitoxin binds to the external pore of the K+ channel between the four subunits of the channel. It can assume any one of four orientations.


(1) http://www.sigmaaldrich.com/catalog/search/SearchResultsPage (2) Garcia ML et al, Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochemistry. 1994 Jun 7;33(22):6834-9. (3) Gao YD et al, Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: selectivity between voltage-gated and Maxi-K channels Proteins. 2003 Aug 1;52(2):146-54. (4)

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Margatoxin". More...

Margatoxin Edit Wikipedia article


Margatoxin ( synonym MgTx) is a toxin that was first found in, and isolated from, the South American scorpion called Centruroides Margaritatus. Because of it's selectivity for blocking Kv1.3 channels, it is used for research on the function of this channel in relation to action potentials in neurons. Further more, it may also have immunosuppresive effects due to the involvement of potassium channels in T lymphocyte activation.


Centruroides Margaritatus also known as the Central American bark scorpion. This is a scorpion that is native to Central and South America. It is from a big scorpion family (Centuroides). They are about 5-8 cm long including their tail.


The genesequence is:

H-Thr-Ile-Ile-Asn-Val-Lys-Cys-Thr-Ser-Pro-Lys-Gln-Cys-Leu-Pro-Pro-Cys-Lys-Ala-Gln-Phe-Gly-Gln-Ser-Ala-Gly-Ala-Lys-Cys-Met-Asn-Gly-Lys-Cys-Lys-Cys-Tyr-Pro-His-OH (Disulfide bonds between Cys7-Cys29, Cys13-Cys34 and Cys17-Cys36) "

The formula of margatoxin is C178 H286 N52 O50 S7

The molecular weight is 4179.0


Margatoxin is a specific blocker for the Kv1.3 channel.

Mode of action

Margatoxin blocks Kv1.3 channels specifically with high affinity ( picomolar concentrations) as a peptidyl inhibitor. These channels play a key role in neurotransmitter release. Blocking these channels results in a loss of current and prevents the neuron from firing actionpotentials, and stabilizes tonic firing under current clamp conditions (3)


Centruroides margaritatus is not deadly but has a painful sting that causes local swelling and tingling (LD50 59.9 mg/kg). This means that if the scorpion stings you, the pain will be gone in 3-4 hours. No extra treatment will be needed. ( Anti-histamines might be suited to prevent an allergic response)


1) Knaus HG, Koch RO, Eberhart A, Kaczorowski GJ, Garcia ML, Slaughter RS.[125I]margatoxin, an extraordinarily high affinity ligand for voltage-gated potassium channels in mammalian brain. Biochemistry. 1995 Oct 17;34(41):13627-34.

2) Garcia-Calvo M, Leonard RJ, Novick J, Stevens SP, Schmalhofer W, Kaczorowski GJ, Garcia ML. Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels. J Biol Chem. 1993 Sep 5;268(25):18866-74.

3) Kupper J, Prinz AA, Fromherz P. Recombinant Kv1.3 potassium channels stabilize tonic firing of cultured rat hippocampal neurons. Pflugers Arch. 2002 Feb;443(4):541-7. Epub 2001 Oct 18.

4) http://www.axxora.com/toxins-ALX-630-045/opfa.1.1.ALX-630-045.1879.4.1.html

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Scorpion toxin". More...

Scorpion toxin Edit Wikipedia article

Scorpion toxin-like domain
OPM superfamily61
OPM protein1djt

Scorpion toxins are proteins, which may be mammal or insect specific, bind to sodium channels, inhibiting the inactivation of activated channels and blocking neuronal transmission. The complete covalent structure of the toxins has been deduced: it comprises around 66 amino acid residues and is cross- linked by 4 disulphide bridges[1][2]. An anti-epilepsy peptide isolated from scorpion venom[3] shows similarity to both scorpion neurotoxins and anti-insect toxins.

This family also contains a group of proteinase inhibitors from Arabidopsis thaliana and Brassica spp., which belong to MEROPS inhibitor family I18, clan I-. The Brassica napus (Oil seed rape) and Sinapis alba (White mustard) inhibitors[4][5], inhibit the catalytic activity of bovine beta-trypsin and bovine alpha-chymotrypsin, which belong to MEROPS peptidase family S1 (InterPro: IPR001254)[6].

This family contains both neurotoxins and plant defensins. The mustard trypsin inhibitor, MTI-2, is plant defensin. It is a potent inhibitor of trypsin with no activity towards chymotrypsin. MTI-2 is toxic for Lepidopteran insects, but has low activity against aphids. Brazzein is plant defensin-like protein. It is pH-stable, heat-stable and intensely sweet protein [7]



  1. ^ Granier C, Kopeyan C, Rochat H, Mansuelle P, Sampieri F, Brando T, Bahraoui EM (1990). "Primary structure of scorpion anti-insect toxins isolated from the venom of Leiurus quinquestriatus quinquestriatus". FEBS Lett. 261 (2): 423–426. PMID 2311768.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Rochat H, Gregoire J (1983). "Covalent structure of toxins I and II from the scorpion Buthus occitanus tunetanus". Toxicon. 21 (1): 153–162. PMID 6845379.
  3. ^ Zhou XH, Yang D, Zhang JH, Liu CM, Lei KJ (1989). "Purification and N-terminal partial sequence of anti-epilepsy peptide from venom of the scorpion Buthus martensii Karsch". Biochem. J. 257 (2): 509–517. PMID 2930463.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Ronchi S, Ceciliani F, Ascenzi P, Bortolotti F, Menegatti E, Palmieri S (1994). "Purification, inhibitory properties, amino acid sequence and identification of the reactive site of a new serine proteinase inhibitor from oil-rape (Brassica napus) seed". FEBS Lett. 342 (2): 221–224. PMID 8143882.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Bolognesi M, Ronchi S, Tedeschi G, Ascenzi P, Bortolotti F, Menegatti E, Palmieri S, Thomas RM (1992). "Purification, inhibitory properties and amino acid sequence of a new serine proteinase inhibitor from white mustard (Sinapis alba L.) seed". FEBS Lett. 301 (1): 10-1 4. PMID 1451776. {{cite journal}}: line feed character in |pages= at position 5 (help)CS1 maint: multiple names: authors list (link)
  6. ^ Rawlings ND, Barrett AJ, Tolle DP (2004). "Evolutionary families of peptidase inhibitors". Biochem. J. 378: -. PMID 14705960.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Sweetness determinant sites of brazzein, a small, heat-stable, sweet-tasting protein. Assa di-Porter FM, Aceti DJ, Markley JL; Arch Biochem Biophys 2000;376:259-265. PMID 10775411
This article incorporates text from the public domain Pfam and InterPro: IPR002061

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Scorpion short toxin, BmKK2 Provide feedback

Members of this family, which are found in various scorpion toxins, confer potassium channel blocking activity [1].

Literature references

  1. Zhang N, Li M, Chen X, Wang Y, Wu G, Hu G, Wu H; , Proteins. 2004;55:835-845.: Solution structure of BmKK2, a new potassium channel blocker from the venom of chinese scorpion Buthus martensi Karsch. PUBMED:15146482 EPMC:15146482

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001947

Scorpion venoms contain a variety of peptides toxic to mammals, insects and crustaceans. Among these peptides there is a family of short toxins (30 to 40 residues) [ PUBMED:7998956 , PUBMED:7819188 ]. This entry represents members of this family with potassium channel blocking activity [ PUBMED:15146482 ]. KTX 12 Sp2 toxin from Scorpiops pococki has shown a strong immunosuppressant effect, being an interesting therapeutic agent for autoimmune disease treatment [ PUBMED:31890149 ]. This entry also includes NU-buthitoxin-Ptr1a, a toxin that acts as an agonist on melanocortin receptors and does not show activity on mammalian sodium or potassium channels [ PUBMED:32602722 ]. Toxin BmK NSPK from Manchurian scorpion, is a voltage-gated potassium (Kv) channel inhibitor that augments neurite extension via NGF/TrkA signaling pathway. As Kv channels may represent molecular targets to modulate spinal cord neurons development and regeneration, they become interesting targets to develop treatments for spinal cord injury [ PUBMED:33466524 ].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan Knottin_1 (CL0054), which has the following description:

This clan includes a number of toxin families that share the knottin structure. These families come from scorpions, plants and arthropods.

The clan contains the following 15 members:

BmKX Defensin_2 Defensin_5 Defensin_like Gamma-thionin Macin SCRL SLR1-BP Toxin_17 Toxin_2 Toxin_3 Toxin_37 Toxin_38 Toxin_5 Toxin_6


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Seed source: Prosite
Previous IDs: toxin_2;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 47
Number in full: 5
Average length of the domain: 32.4 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 40.3 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.1 25.1
Trusted cut-off 25.1 25.2
Noise cut-off 25.0 24.6
Model length: 32
Family (HMM) version: 22
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Toxin_2 domain has been found. There are 104 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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