# Calitoxin
**Calitoxin** (CLX) is a neurotoxic peptide isolated from the sea anemone *Calliactis parasitica*, a small hormathiid anemone that lives in symbiosis with hermit crabs. The mature toxin is a 46-residue polypeptide with a molecular mass of 4886 Da and an isoelectric point at pH 5.4, and its amino acid sequence differs greatly from those of other [sea anemone toxins](https://www.edgepedia.org/sea-anemone-toxin).[1](https://pubmed.ncbi.nlm.nih.gov/2567180/) Two nearly identical forms, calitoxin I (CLX-I) and calitoxin II (CLX-II), are produced by the anemone and are classified together as the type 4 family of sea anemone sodium channel toxins.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/)
| Key fact | Detail |
|---|---|
| Source organism | The sea anemone *Calliactis parasitica* (Hormathiidae), which inhabits marine biocenoses in symbiosis with hermit crabs[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9863223/) |
| Mature toxin size | 46 amino acid residues, molecular mass 4886 Da, isoelectric point pH 5.4[1](https://pubmed.ncbi.nlm.nih.gov/2567180/) |
| Isoforms | Calitoxin I (Δ-hormotoxin-Cpt1a) and calitoxin II (Δ-hormotoxin-Cpt1b), the only two members of the Na\(_{V}\) type 4 sea anemone toxin family, differing by a single amino acid[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/) |
| Disulfide bridges | Three, with a topology similar to that of type 1 and 2 sea anemone toxins, but only about 45% sequence identity to them[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9863223/) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/) |
| Target | Voltage-gated sodium channels, acting probably in a manner similar to type 1–3 sea anemone toxins[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4271777/) |
| Effect in crustacean preparations | Acts on axonal rather than muscle membranes, inducing massive neurotransmitter release and strong muscle contraction[1](https://pubmed.ncbi.nlm.nih.gov/2567180/) |
| Genes | clx-1 and clx-2, each with two introns and three exons, 95% identical, encoding 79-residue precursors[5](https://pubmed.ncbi.nlm.nih.gov/7510258/) |
## Discovery and sequence
Calitoxin was isolated from *Calliactis parasitica* by a team at the Biochemistry Laboratory of the Stazione Zoologica di Napoli, Italy, and described in *Biochemistry* in 1989 by Lucio Cariello and colleagues.[1](https://pubmed.ncbi.nlm.nih.gov/2567180/) The sequence was determined by [Edman degradation](https://www.edgepedia.org/edman-degradation) of the reduced, S-carboxymethylated polypeptide chain and of tryptic and chymotryptic peptides, beginning Ile-Glu-Cys-Lys-Cys-Glu-Gly-Asp-Ala-Pro and ending Asp-Cys-Cys-His-Glu-Ala.[1](https://pubmed.ncbi.nlm.nih.gov/2567180/) The authors noted that the low homology of calitoxin with the toxins Rp II and ATX II has implications for the roles played by particular amino acid residues.[1](https://pubmed.ncbi.nlm.nih.gov/2567180/)
Later surveys of sea anemone peptide toxins placed calitoxin outside the three classical structural types of sodium channel toxins. Type 1 and 2 toxins contain 46 to 51 residues and type 3 toxins 27 to 32 residues, while the calitoxins match the longer types in chain length and disulfide bridge pattern but differ greatly in sequence.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4271777/) A 1996 study of toxins from *Anemonia erythraea* likewise singled out calitoxin, together with BTTX II from *Bolocera tuediae*, as remote from the type 1–3 category.[6](https://www.sciencedirect.com/science/article/abs/pii/S0304416596001377)
## The two isoforms and their genes
**Two genes, one substitution.** In 1994, Spagnuolo, Zanetti, Cariello, and Piccoli isolated and characterized two genes, clx-1 and clx-2, from a *C. parasitica* [genomic library](https://www.edgepedia.org/genomic-library). The clx-1 gene encodes the already known calitoxin sequence, named CLX-I, while a single base-pair substitution in the coding region of clx-2 produces a single Glu-to-Lys replacement in a new peptide, CLX-II. The two genes share 95% sequence identity across their two introns and three exons, and both open reading frames encode a precursor peptide of 79 residues whose [N-terminus](https://www.edgepedia.org/n-terminus) has the features of a signal peptide; a pair of basic residues upstream of each mature toxin suggests proteolytic cleavage releases the neurotoxins from their precursors.[5](https://pubmed.ncbi.nlm.nih.gov/7510258/)
Reviews differ in how they number the differing residue: the 1994 gene paper places the Glu/Lys replacement at position 6,[5](https://pubmed.ncbi.nlm.nih.gov/7510258/) while a 2019 structural overview describes the single difference as Glu8 versus Lys8.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/) Both agree that the two mature toxins of 46 residues differ by only this one amino acid.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/) • [5](https://pubmed.ncbi.nlm.nih.gov/7510258/)
## Mechanism of action
Like other sea anemone sodium channel toxins, calitoxin acts on voltage-gated sodium channels, probably in a manner similar to the type 1–3 toxins, which typically bind to receptor site 3 and delay channel inactivation.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4271777/) In crustacean nerve-muscle preparations, calitoxin interacts with axonal membranes and not with muscle membranes, inducing a massive release of neurotransmitter that causes a strong muscle contraction.[1](https://pubmed.ncbi.nlm.nih.gov/2567180/) A cnidarian toxin review lists calitoxin 1 with an LD\(_{50}\) of about 5 and describes increased transmitter release causing repetitive firing of the axons in crustacean neuromuscular preparations.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC7600780/) Surface residues of the toxin form a hydrophobic region that may represent a sodium channel binding surface.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9863223/)
## Classification
The 2019 structural overview of sea anemone toxins assigns the calitoxins to the Na\(_{V}\) type 4 toxin family, which comprises only the two isotoxins calitoxin I (Δ-hormotoxin-Cpt1a) and calitoxin II (Δ-hormotoxin-Cpt1b) from *Calliactis parasitica*.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/) A 2021 review of marine toxins targeting voltage-gated sodium channels also places calitoxin I and II in the type IV toxins, although it describes them as 79 amino acid residues long, the length of the precursor rather than the 46-residue mature peptide reported in the original isolation.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC8537899/) • [1](https://pubmed.ncbi.nlm.nih.gov/2567180/) Some other reviews have left the calitoxins unallocated to a separate group while noting their structural distinctness.[9](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/sea-anemone-toxin) Neurotoxins of types 3 and 4, whose sequences differ significantly from types 1 and 2, appear to be less abundant in sea anemone venoms.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9863223/) A calitoxin-like sequence has also been detected with high coverage in the secreted venom of the related anemone *Calliactis polypus*, raising the question of whether the toxin is recruited throughout the body plan of *Calliactis* species.[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC11299110/)
## References
1. [Cariello L, de Santis A, Fiore F, Piccoli R, Spagnuolo A, Zanetti L, Parente A (1989). Calitoxin, a neurotoxic peptide from the sea anemone *Calliactis parasitica*: amino acid sequence and electrophysiological properties. *Biochemistry* 28(6):2484–2489.](https://pubmed.ncbi.nlm.nih.gov/2567180/)
2. [Madio B, King GF, Undheim EAB (2019). Sea Anemone Toxins: A Structural Overview. *Marine Drugs* 17(6):325.](https://pmc.ncbi.nlm.nih.gov/articles/PMC6627431/)
3. [Kozlova E, et al. (2023). The Sea Anemone Neurotoxins Modulating Sodium Channels: An Insight at Structure and Functional Activity after Four Decades of Investigation. *Toxins* 15(1):8.](https://pmc.ncbi.nlm.nih.gov/articles/PMC9863223/)
4. [Shiomi K (2006). Peptide Toxins in Sea Anemones: Structural and Functional Aspects. *Marine Biotechnology*.](https://pmc.ncbi.nlm.nih.gov/articles/PMC4271777/)
5. [Spagnuolo A, Zanetti L, Cariello L, Piccoli R (1994). Isolation and characterization of two genes encoding calitoxins, neurotoxic peptides from *Calliactis parasitica* (Cnidaria). *Gene* 138:187–191.](https://pubmed.ncbi.nlm.nih.gov/7510258/)
6. [Lin X, et al. (1996). Novel polypeptide toxins with crab lethality from the sea anemone *Anemonia erythraea*. *Biochimica et Biophysica Acta*.](https://www.sciencedirect.com/science/article/abs/pii/S0304416596001377)
7. [A Review of Toxins from Cnidaria (2020). *Marine Drugs* 18(10):507.](https://pmc.ncbi.nlm.nih.gov/articles/PMC7600780/)
8. [Mackieh R, et al. (2021). Voltage-Gated Sodium Channels: A Prominent Target of Marine Toxins. *Marine Drugs* 19(10):562.](https://pmc.ncbi.nlm.nih.gov/articles/PMC8537899/)
9. [Sea Anemone Toxin – an overview, ScienceDirect Topics.](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/sea-anemone-toxin)
10. [Smith HL, et al. (2024). Molecular Insights into the Low Complexity Secreted Venom of *Calliactis polypus*.](https://pmc.ncbi.nlm.nih.gov/articles/PMC11299110/)
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*Topic: Encyclopedia › Life and health › Animals › Invertebrates › Other invertebrate lineages › Cnidarians and ctenophores › Anthozoans › Hexacorallia › Sea anemones (Actiniaria) › Anemone toxins and venoms*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license