TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
1.C.38.1.1









Equinatoxin II (EqtII) binds sphingomyelin specifically and localizes to the Golgi apparatus (Bakrac et al., 2010).  Disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII) and sticholysin II (StII) impairs the pore formation activity (Mesa-Galloso et al. 2016). Reviewed by Gupta et al. 2023.

Eukaryota
Metazoa, Cnidaria
Equinatoxin of Actinia tenebrosa (P61915)
1.C.38.1.2









Sticholysin I (cytolysin ST1; STNI STII; StiII; FraC) (Alvarez et al., 2009). Pore formation goes through a dimer intermediate and then generates the active octamer. Disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII) and sticholysin II (StII) impairs the pore formation activity (Mesa-Galloso et al. 2016). Sticholysin II-mediated cytotoxicity may involve the activation of regulated intracellular responses that anticipates cell death (Soto et al. 2018). Sticholysins represent a prototype of proteins acting through the formation of protein-lipid toroidal pores. Peptides spanning the N-terminus of sticholysins mimic the permeabilizing activity of the full-length toxins (Mesa-Galloso et al. 2019). Phospholipids integrate into the ring of the toroidal pores, promoting their stabilization. Self-association and folding in the membrane determine the mode of action of peptides from the lytic segment of sticholysins (Ros et al. 2019). STNI and STNII are 94% identical. They form cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and cytolysis. Lanio et al. 2001 showed that pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using an aromatic rich region and an adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of monomers. Cytolytic effects include red blood cell hemolysis, platelet aggregation and lysis, cytotoxic and cytostatic effects on fibroblasts. Lethality in mammals has been ascribed to severe vasospasm of coronary vessels, cardiac arrhythmia, and inotropic effects (Lanio et al. 2001).

Eukaryota
Metazoa, Cnidaria
Sticholysin I of Stichodactyla helianthus
1.C.38.1.3









Tenebrosin-A (fragment)
Eukaryota
Metazoa, Cnidaria
Tenebrosin-A of Actinia tenebrosa (P30833)
1.C.38.1.4









Actinoporin Or-A, cation-selective pore forming tetrameric toxin
Eukaryota
Metazoa, Cnidaria
Actinoporin Or-A of Oulactis orientalis (sea anenome) (Q5I4B8)
1.C.38.1.5









Echotoxin-2 precursor, Echt-2 hemolysin (276 aas). Pore-forming protein; forms cation-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves recognition of membrane sphingomyelin using aromatic rich regions and adjacent phosphocholine binding sites for firm binding to the membrane accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of several monomers (Kawashima et al., 2003; Shiomi et al., 2002).

Eukaryota
Metazoa, Mollusca
Echt-2 hemolysin of Monplex echo (a marine gastropod)
(Q76CA2)
1.C.38.1.6









Cytolytic pore-forming tetrameric toxin (forms cation-selective pores (d = 1 nm) (Mebs et al., 1992).
Eukaryota
Metazoa, Cnidaria
Cytolysin of Heteractis magnifica
(P39088)
1.C.38.1.7









The plant actinoporin homologue (293aas). Function unknown.
Eukaryota
Viridiplantae
Actinoporin homologue of Physcomitrella patens (A9S8W4)
1.C.38.1.8









Fragaceatoxin C (FraC) of the strawberry anemone (Structure solved to 1.8 Å resolution (PPDB acc # 4TSL); It is a crown-shaped nonamer with an external diameter of about 11.0 nm and an internal diameter of approximately 5.0 nm.) Almost identical to Equinatoxin II/Tenebrosin C (1.C.38.1.1) (Mechaly et al., 2011).  Fragaceatoxin C (FraC) is an α-barrel pore-forming toxin (PFT). The crystal structures of FraC at four different stages of the lytic mechanism have been determined at 3.1Å resolution, namely the water-soluble state, the monomeric lipid-bound form, an assembly intermediate and the fully assembled transmembrane pore (Tanaka et al. 2015). The structure of the transmembrane pore exhibits a unique architecture composed of both protein and lipids, with some of the lipids lining the pore wall, acting as assembly cofactors. The pore exhibits lateral fenestrations that expose the hydrophobic core of the membrane to the aqueous environment. The incorporation of lipids from the target membrane within the structure of the pore provides a membrane-specific trigger for the activation of this haemolytic toxin.  It has been reconstituted in  planar lipid bilayers and engineered for DNA analysis.  It shows a funnel-shaped geometry that allows tight wrapping around single-stranded DNA (ssDNA), resolving between homopolymeric C, T, and A polynucleotide stretches (Wloka et al. 2016). Despite the 1.2 nm internal constriction in the FraC pore, double-stranded DNA (dsDNA) can translocate through the nanopore at high applied potentials, presumably through deformation of the alpha-helical transmembrane region (Huang et al. 2017). Therefore, FraC nanopores might be useful for DNA sequencing and dsDNA analysis. Pore formation goes through a dimer intermediate and then generates the active octamer. Disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII) and sticholysin II (StII) impairs the pore formation activity (Mesa-Galloso et al. 2016). It was reviewed by Gupta et al. 2023. FraE is almot identical to this protein.

Eukaryota
Metazoa, Cnidaria
FraC of Actine fragacea (B9W5G6)
1.C.38.1.9









Equinatoxin 5 of 214 aas (Frazão et al. 2012). Bryoporin-7 (P61914; 214 aas) is 83% identical.

Eukaryota
Metazoa, Cnidaria
Equinatoxin-5 of Actinia equina
1.C.38.1.10









Cytolysin RTX-A of 175 aas. Forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) and requires oligomerization of the toxin subunits (Frazão et al. 2012). 

Eukaryota
Metazoa, Cnidaria
Cytolysin RTX-A of Heteactis crispa (Radianthus macrodactylus) (Leathery sea anemone)
1.C.38.1.11









Cytolysin Src-1 of 216 aas (Frazão et al. 2012).

Eukaryota
Metazoa
Cytolysin Src-1 of Sagartia rosea (sea anemone)
1.C.38.1.12









Fragaceatoxin C (FraC), an alpha-barrel pore-forming protein, a cytolytic actinoporin, of 152 aas (Morante et al. 2015; Rojko et al. 2015).  Pore formation goes through a dimer intermediate and then generates the active octamer. Disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII) and sticholysin II (StII) impairs the pore formation activity (Mesa-Galloso et al. 2016).

Eukaryota
Metazoa, Chordata
FraC of Callorhynchus milii
1.C.38.1.13









Conoporin 1 of 242 aas

Eukaryota
Metazoa, Mollusca
Conotoxin 1 of Conus geographus (Geography cone) (Nubecula geographus)
1.C.38.1.14









Pore-forming toxin, Nigrelysin of 214 aas. The toxin lacks Cys and readily permeabilizes erythrocytes, as well as L1210 cells. CD spectroscopy revealed that its secondary structure is dominated by beta structure (58.5%) with 5.5% α-helix, and 35% random structure. Binding experiments to lipidic monolayers and to liposomes, as well as permeabilization studies in vesicles, revealed that the affinity of this toxin for sphingomyelin-containing membranes is quite similar to sticholysin II (StII) (Alvarado-Mesén et al. 2019).

Eukaryota
Metazoa, Cnidaria
Nigrelysin of Anthopleura nigrescens
1.C.38.1.15









Pore-forming cytolysin, Src-1-like, isoform X1 of 225 aas (Borges et al. 2018).

Eukaryota
Metazoa, Chordata
Cytolysin of Notothenia coriiceps
1.C.38.1.16









Bryoporin of 178 aas, possibly with an N-terminal TMS.  It has hemolytic activity in vitro and probably binds a phosphocholine derivative with the unique amido or hydroxyl groups found in sphingomyelin. It is involved in drought tolerance and is inhibited by sphingomyelin (Hoang et al. 2009). Pore-forming moss protein bryoporin is structurally and mechanistically related to actinoporins from evolutionarily distant cnidarians (Šolinc et al. 2022).

Eukaryota
Viridiplantae, Streptophyta
Bryoporin of Physcomitrium pates (spreading leaved earth moss) (Physcomitrella patens)
1.C.38.1.17









Sticholysin II, EstII; She4, of 175 aas. Its 3-D structure has been solved (1GWY).

Eukaryota
Metazoa, Cnidaria
She4 of Stichodactyla helianthus
1.C.38.1.18









Hydra Actinoporin-like toxin 1 of 187 aas. The 3-D structure is known (PDB acc# 7EKZ).

Eukaryota
Metazoa, Cnidaria
Toxin of Hydra vulgaris (Hydra attenuata)