Summary: Ion channel inhibitory toxin
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Spider toxin Edit Wikipedia article
|SCOPe||1oav / SUPFAM|
|SCOPe||1qdp / SUPFAM|
|Spider toxin CSTX family|
|Spider potassium channel inhibitory toxin|
|SCOPe||1d1h / SUPFAM|
A remotely related group of atracotoxins operate by opening sodium channels. Î´-Atracotoxin from the venom of the Sydney funnel-web spider produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels. The structure of atracotoxin comprises a core beta region containing a triple-stranded a thumb-like extension protruding from the beta region and a C-terminal helix. The beta region contains a cystine knot motif, a feature seen in other neurotoxic polypeptides and other spider toxins, of the CSTX family.
Spider potassium channel inhibitory toxins is another group of spider toxins. A representative of this group is hanatoxin, a 35 amino acid peptide toxin which was isolated from Chilean rose tarantula (Grammostola rosea, syn. G. spatulata) venom. It inhibits the drk1 voltage-gated potassium channel by altering the energetics of gating. See also Huwentoxin-1 InterPro: IPR013140.
- doi:10.1038/nsb1294-853. PMID 7773772. ; Reily MD, Holub KE, Gray WR, Norris TM, Adams ME (December 1994). "Structure-activity relationships for P-type calcium channel-selective omega-agatoxins". Nat. Struct. Biol. 1 (12): 853â€“6.
- Mackay JP, King GF, Fletcher JI, Chapman BE, Howden ME (1997). "The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel". Structure. 5 (11): 1525â€“1535. doi:10.1016/S0969-2126(97)00301-8. PMID 9384567.
- Shimada I, Sato K, Takahashi H, Kim JI, Min HJ, Swartz KJ (2000). "Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins". J. Mol. Biol. 297 (3): 771â€“780. doi:10.1006/jmbi.2000.3609. PMID 10731427.
- Kim JI, Konishi S, Iwai H, Kohno T, Gouda H, Shimada I, Sato K, Arata Y (July 1995). "Three-dimensional solution structure of the calcium channel antagonist omega-agatoxin IVA: consensus molecular folding of calcium channel blockers". J. Mol. Biol. 250 (5): 659â€“71. doi:10.1006/jmbi.1995.0406. PMID 7623383.
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Ion channel inhibitory toxin Provide feedback
This is a family of potent toxins that function as ion-channel inhibitors for several different ions. Omega-Grammotoxin SIA is a VSCC antagonist that inhibits neuronal N- and P-type VSCC responses . Huwentoxin-IV, from the Chinese bird spider, is a highly potent neurotoxin that specifically inhibits the neuronal tetrodotoxin-sensitive voltage-gated sodium channel in rat dorsal root ganglion neurons . Hainantoxin-4, from the venom of spider Selenocosmia hainana, adopts an inhibitor cystine knot structural motif like huwentoin-IV, and is a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels . Study of the molecular nature of toxin-receptor interactions has helped elucidate the functioning of many ion-channels .
Lampe RA, Defeo PA, Davison MD, Young J, Herman JL, Spreen RC, Horn MB, Mangano TJ, Keith RA;, Mol Pharmacol. 1993;44:451-460.: Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. PUBMED:8394998 EPMC:8394998
Peng K, Shu Q, Liu Z, Liang S;, J Biol Chem. 2002;277:47564-47571.: Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. PUBMED:12228241 EPMC:12228241
Liu Z, Dai J, Chen Z, Hu W, Xiao Y, Liang S;, Cell Mol Life Sci. 2003;60:972-978.: Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana. PUBMED:12827284 EPMC:12827284
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR011696
This is a family of potent toxins that function as ion-channel inhibitors. Omega-Grammotoxin SIA is a VSCC antagonist that inhibits neuronal N- and P-type VSCC responses [ PUBMED:8394998 ]. Huwentoxin-IV, from the Chinese bird spider, is a highly potent neurotoxin that specifically inhibits the neuronal tetrodotoxin-sensitive voltage-gated sodium channel in rat dorsal root ganglion neurons [ PUBMED:12228241 ]. Hainantoxin-4, from the venom of spider Selenocosmia hainana, adopts an inhibitor cystine knot structural motif like huwentoin-IV, and is a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels [ PUBMED:12827284 ]. Study of the molecular nature of toxin-receptor interactions has helped elucidate the functioning of many ion-channels [ PUBMED:20189991 ]. Some members of this family, Tap1 and Tap2, can modulate the activity of both voltage-gated sodium and calcium channels which are implicated in the etiology of chronic pain, being interesting for chronic pain treatment [ PUBMED:32826759 , PUBMED:30784059 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extracellular region (GO:0005576)|
|Molecular function||ion channel inhibitor activity (GO:0008200)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan contains a set of related small protein toxins and what appears to be the functionally distinct Albumin I domain. All members of this clan have a knottin-like fold. Additional information about this clan may be found from .
The clan contains the following 36 members:ACI44 Agouti Albumin_I Albumin_I_a Antifungal_pept Antimicrobial25 Argos Atracotoxin CART CBM_1 Chi-conotoxin Conotoxin DUF5637 LEAP-2 Mu-conotoxin Omega-toxin Tachystatin_A Tachystatin_B Toxin_11 Toxin_12 Toxin_16 Toxin_18 Toxin_20 Toxin_21 Toxin_22 Toxin_23 Toxin_24 Toxin_27 Toxin_28 Toxin_30 Toxin_35 Toxin_7 Toxin_9 Tryp_inh UPF0506 Viral_cys_rich
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Key: available, not generated, — not available.
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|Seed source:||Pfam-B_20319 (release 14.0)|
|Author:||Bateman A , Finn RD|
|Number in seed:||31|
|Number in full:||27|
|Average length of the domain:||30.20 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||19.41 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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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_12 domain has been found. There are 53 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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