Please help us understand the impact of EMBL-EBI services, including Pfam, by filling out a short survey →
Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 0  species 0  interactions 0  sequences 0  architectures

Family: Atracotoxin (PF05353)

Summary: Delta Atracotoxin

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 "Delta atracotoxin". More...

Delta atracotoxin Edit Wikipedia article

Delta Atracotoxin
ACTX spider toxin 1QDP.png
3D stick model of delta-atracotoxin-Ar1 (robustoxin)
OPM superfamily112
OPM protein1vtx

Delta atracotoxin (δ-ACTX-Ar1, robustoxin, or robustotoxin) is a low-molecular-weight neurotoxic polypeptide found in the venom of the Sydney funnel-web spider (Atrax robustus).

Delta atracotoxin produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of sodium ion channels in autonomic and motor neurons. In the spiders' intended insect prey, the toxin exerts this same activity upon potassium and calcium ion channels.[1]

The structure of atracotoxin comprises a core beta region with a cystine knot motif, a feature seen in other neurotoxic polypeptides.[1][2]


Since 1927, records are kept of envenomations by the Sydney funnel-web spider and 14 deaths have been reported in medical literature between 1927 and 1981, when the antivenom became available. In all cases in which the sex of the spider was determined, death occurred after a bite from a male spider.[3]


Delta atracotoxin is a 42-residue peptide toxin. The amino acid sequence of delta atracotoxin is unusual in that it contains three consecutive cysteine residues at positions 14–16. The amino acid sequence of delta atracotoxin is:


Cysteine bridges exist between Cys1 and Cys15, Cys8 and Cys20, Cys14 and Cys31, and Cys16 and Cys42.

The structure consists of a small triple-stranded beta-sheet stabilized by a disulfide knot, followed by a C-terminal extension comprising three classic or inverse y-turns. The disulfide knot is a ring consisting of two disulfide bonds (1-15 and 8-20) and the connecting backbone, through which a third disulfide bond (14-31) passes. The β-sheet, defined on the basis of inter-sheet hydrogen bonds, consists of residues 6-8 (strand I), 19-21 (strand II) and 29-32 (strand III), with a topology of +2x, —1. The two hydrogen bonds (one amide of which has a slowly exchanging amide proton) between strands I and III are distorted (NH to CO distance between 2.5 and 3.0 A). There are four hydrogen bonds between strands II and III (all of which have corresponding slowly exchanging amide protons), three being present in most of the structures and one in half of the structures. The structure contains a number of chain reversals. The first is not well defined and is either a type II ß-turn (Lys3-Asn6) or a y-turn centered on Arg5. Chain reversal II is a y turn centered on Gly9. Chain reversal III is not well defined, being either a type I ß-turn (Asnn-Cys14) or an inverse y-turn centered on Asn11. Chain reversal IV (Cys15-Met18) is not stabilized by a hydrogen bond but has a cis peptide bond between Cys16 and Pro17 and resembles a type Via turn. The fifth chain reversal occurs in the region of residues 22-28, which fulfill the criteria for an i2-loop. The C-terminal extension, stabilized by the Cys16-Cys42 disulfide bond, consists of three y-turns, VI-VIII, that are, respectively, an inverse turn, centered on Thr33, a classic turn centered on Ile35 and an inverse turn centered on Phe39. All three of the y-turn hydrogen bonds have slowly exchanging amide protons (although this is not the case for the other turns). The only slowly exchanging amide proton not accounted for by consensus hydrogen bonds in any secondary structure element is that of Gly37 (which hydrogen bonds to Thr34 in one of the structures). The conformations of the Cys1-Cys15 and Cys8-Cys20 disulfide bonds are well defined and have negative and positive Xss, respectively; the other two bonds have lower order parameters. The hydrophobic core of RBX is limited, consisting of essentially the disulfide knot cystine residues and the buried Met18. However, the 22-28 loop contains one apolar residue, Ala23, and three aromatics, Tyr22, Trp24 and Tyr25, and is flanked by Ile21 at its N-terminus and Trp7 near its C-terminus, so this region represents a significant non-polar surface on the molecule. RBX is highly positively charged, with one Arg (sequence position 5) and six Lys (3, 4, 10, 19, 40 and 41) residues, balanced only by Glu12 and Asp13. These charged residues form three patches on the surface. Patch A consists of the positively charged residues 3,4 and 5, patch B of residues 10, 12, 13 and the N-terminus (including possible salt bridges between Lys10 and Glu12 and Asp13 and the N-terminus), and patch C of 19, 40, 41 and the C-terminus.[2]

Mechanism of action


Delta atracotoxin is responsible for the potentially lethal envenomation syndrome seen following funnel-web spider envenomation. d-Atracotoxins induce spontaneous, repetitive firing and prolongation of action potentials resulting in continuous acetylcholine neurotransmitter release from somatic and autonomic nerve endings. This will lead to slower voltage-gated sodium channel inactivation and a hyperpolarizing shift in the voltage-dependence of activation. This action is due to voltage-dependent binding to neurotoxin receptor site-3 in a similar, but not identical, fashion to scorpion a-toxins and sea anemone toxins. In the sea anemone and scorpion toxins, combinations of charged (especially cationic) and hydrophobic side-chains are important for binding to their receptor site (site 3) on the sodium channel. It will therefore be not surprising to find that the same applies to delta atracotoxin and versutoxin (a close homologue of delta atracotoxin). Delta atracotoxin presents three distinct charged patches on its surface, as well as a non-polar region centered on the 22-28 loop. Both of these structural features may play a role in its binding to the voltage-gated sodium channel, but further studies are necessary in defining which residues are important for interaction with the sodium channel so that a plausible model can be constructed of its binding site.[2]

Mechanism of action of synthetic d-ACTX

The availability of synthetic toxin has allowed scientist to further explore the biological activity of the toxin, resulting in the observation that d-ACTX-Ar1a causes repetitive firing and prolongation of the action potential. These actions underlie the clinical symptoms seen following envenomation and further contribute to the understanding of the molecular basis for activity of this potent neurotoxin on voltage-gated sodium channels.

Under voltage-clamp conditions in dorsal root ganglion (DRG) neurons is found that the effects of the synthetic toxin on sodium currents were not significantly different from those previously reported for the native toxin. Neither native nor synthetic d-ACTX-Ar1a had any effect on TTX-resistant sodium currents, but both exerted a potent selective modulation of TTX-sensitive sodium currents consistent with actions on neurotoxin receptor site-3. This includes a slowing of the sodium-channel inactivation, a hyperpolarizing shift in the voltage-dependence of activation and a hyperpolarizing shift in the steady-state sodium-channel inactivation.

d-ACTX-Ar1a causes a prolongation of action potential duration, accompanied by spontaneous repetitive firing, but does not depolarize the resting membrane potential. Effects on the autonomic nervous system, including vomiting, profuse sweating, salivation, lachrymation, marked hypertension followed by hypotension, together with effect on the somatic nervous system to cause muscle fasciculation and dyspnea (shortness of breath) are presumably due to excessive transmitter release. To identify the sodium-channel binding surface of d-ACTX-Ar1a, scientist must synthesize analogues with selected residue changes. Studies will contribute to a more detailed mapping of site-3, the neurotoxin receptor site on the sodium-channel and provide structure-activity data critical for determining the phylaspecific actions of this and related atracotoxins.[2][4][5]

Signs and symptoms

The bite of a Sydney funnel web spider is at first painful, due to the large fangs and acidic pH of the venom. If there is no immediate treatment symptoms may arise beginning 10 minutes after the bite.[3] Hypertension may occur, which is often followed by a prolonged hypotension and circulatory failure. Other symptoms include dyspnea and ultimately respiratory failure, generalized skeletal muscle fasciculation, salivation, lachrymation, sweating, nausea, vomiting, diarrhoea, pulmonary edema and pain.

The progress of the envenomation is precisely studied in primates, which symptoms are very similar to those of humans. In the first 25 minutes after envenomation disturbances in respiration occur, which gradually become worse. Some monkeys required artificial ventilation. Initially, the blood pressure decreased, but then quickly rose, after which the blood pressure gradually declined. After 40–100 minutes severe hypotension occurred. Lachrymation started after 6–15 minutes and was followed by salivation. These symptoms were most severe during 15–35 minutes after envenomation. Skeletal muscle fasciculation started after 8–10 minutes and reached its peak between 20–45 minutes. It was accompanied with an increase in body temperature.

Envenomation with the male venom produced mostly the same symptoms, although the onset of the symptoms was a little delayed. The female venom also produces the same symptoms, but far less severe.[6]


The toxicity of the spider’s venom is affected by the sex of the spider. The male funnel-web spider’s venom appears to be six times more powerful than that of the female spider, based on minimum lethal dose determinations. In addition, different species of animals tend to react to the venom in various ways. For example, rats, rabbits and cats are unaffected by the bite of a female funnel-web spider, whereas for 20 percent of mice and guinea pigs the bite of a female was fatal. A bite of a male funnel-web spider, though, led to the death of almost all mice and guinea pigs. Although the male spider’s venom seems to be more potent, male spider bites cause mild transient effects in dogs and cats. Most primates, including humans, appear to be extremely sensitive to the funnel-web spider’s venom.[7]

The LD50 values have been determined in mice, for male spider venom 3.3 mg/kg body weight of the mouse and for female spider venom 50 mg/kg body weight were found. The LD50 value of pure delta atracotoxin which was isolated from a male spider, 0.15 mg/kg body weight was found.[8]


The antivenom was developed by a team headed by Struan Sutherland at the Commonwealth Serum Laboratories in Melbourne. Since the antivenom became available in 1981, there have been no recorded fatalities from Sydney funnel-web spider bites. In September 2012, it was reported that stocks of antivenom were running low, and members of the public were asked to catch the spiders so that they could be milked for their venom. The venom is taken from the spiders by delicately stroking their fangs and collecting the tiny droplets of the deadly venom. The venom is needed to produce the antivenom. One dose of antivenom requires around 70 milkings from a spider.

Funnel web spider antivenom is prepared from the plasma of rabbits immunized with the venom of the male funnel web spider (Atrax robustus). Each vial of the product contains 125 units of antivenom which has been standardized to neutralize 1.25 mg of funnel web spider venom. The product also contains glycine and other rabbit plasma proteins.

Funnel web spider antivenom is a purified immunoglobulin (mainly immunoglobulin G), derived from rabbit plasma, which contains specific antibodies against the toxic substances in the venom of the funnel web spider, Atrax robustus. There is evidence to show that the antivenom is effective in the treatment of patients bitten by some other funnel web spiders of the genus Hadronyche (formerly Atrax).[9]


  1. ^ a b Fletcher JI, Chapman BE, Mackay JP, Howden ME, King GF (November 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): 1525–35. doi:10.1016/S0969-2126(97)00301-8. PMID 9384567.
  2. ^ a b c d Pallaghy PK, Alewood D, Alewood PF, Norton RS (December 1997). "Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus". FEBS Letters. 419 (2–3): 191–6. doi:10.1016/S0014-5793(97)01452-X. PMID 9428632.
  3. ^ a b Nicholson GM, Graudins A (September 2002). "Spiders of medical importance in the Asia-Pacific: atracotoxin, latrotoxin and related spider neurotoxins". Clinical and Experimental Pharmacology & Physiology. 29 (9): 785–94. doi:10.1046/j.1440-1681.2002.03741.x. PMID 12165044.
  4. ^ Nicholson GM, Little MJ, Birinyi-Strachan LC (April 2004). "Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel". Toxicon. 43 (5): 587–99. doi:10.1016/j.toxicon.2004.02.006. PMID 15066415.
  5. ^ Alewood D, Birinyi-Strachan LC, Pallaghy PK, Norton RS, Nicholson GM, Alewood PF (November 2003). "Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus)". Biochemistry. 42 (44): 12933–40. doi:10.1021/bi030091n. PMID 14596608.
  6. ^ Mylecharane EJ, Spence I, Sheumack DD, Claassens R, Howden ME (1989). "Actions of robustoxin, a neurotoxic polypeptide from the venom of the male funnel-web spider (Atrax robustus), in anaesthetized monkeys". Toxicon. 27 (4): 481–92. doi:10.1016/0041-0101(89)90211-0. PMID 2728033.
  7. ^ Gupta RC (2012). Veterinary toxicology basic and clinical principles (2nd ed.). Amsterdam: Elsevier. ISBN 978-0-12-385927-3.
  8. ^ Sheumack DD, Baldo BA, Carroll PR, Hampson F, Howden ME, Skorulis A (1984). "A comparative study of properties and toxic constituents of funnel web spider (Atrax) venoms". Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology. 78 (1): 55–68. doi:10.1016/0742-8413(84)90048-3. PMID 6146485.
  9. ^ "Funnel web spider antivenom - Product information" (PDF). CSL Limited. Archived from the original (PDF) on 21 April 2013.

External links

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.

Delta Atracotoxin Provide feedback

Delta atracotoxin produces potentially fatal neurotoxic symptoms in primates by slowing he inactivation of voltage-gated sodium channels [1]. 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 [1].

Literature references

  1. Fletcher JI, Chapman BE, Mackay JP, Howden ME, King GF; , Structure 1997;5:1525-1535.: The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel. PUBMED:9384567 EPMC:9384567

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008017

Delta atracotoxin produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels [PUBMED:9384567]. 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 [PUBMED:9384567].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Omega_toxin (CL0083), which has the following description:

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 [1].

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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View            View  View   
HTML View                 
PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download             Download   Download    
Gzipped Download             Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_30981 (release 7.8)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD
Number in seed: 5
Number in full: 0
Average length of the domain: 0.00 aa
Average identity of full alignment: 0 %
Average coverage of the sequence by the domain: 0.00 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 35.0 76.1
Noise cut-off 21.3 19.9
Model length: 42
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.